ID GBA1_HUMAN Reviewed; 536 AA. AC P04062; A8K796; B7Z5G2; B7Z6S1; J3KQG4; J3KQK9; Q16545; Q4VX22; Q6I9R6; AC Q9UMJ8; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 09-NOV-2004, sequence version 3. DT 27-MAR-2024, entry version 266. DE RecName: Full=Lysosomal acid glucosylceramidase {ECO:0000305}; DE Short=Lysosomal acid GCase {ECO:0000303|PubMed:24211208}; DE EC=3.2.1.45 {ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204, ECO:0000269|PubMed:9201993}; DE AltName: Full=Acid beta-glucosidase; DE AltName: Full=Alglucerase; DE AltName: Full=Beta-glucocerebrosidase; DE Short=Beta-GC; DE AltName: Full=Beta-glucosylceramidase 1; DE AltName: Full=Cholesterol glucosyltransferase {ECO:0000305|PubMed:24211208}; DE Short=SGTase {ECO:0000303|PubMed:24211208}; DE EC=2.4.1.- {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:32144204}; DE AltName: Full=Cholesteryl-beta-glucosidase {ECO:0000305|PubMed:24211208}; DE EC=3.2.1.- {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:32144204}; DE AltName: Full=D-glucosyl-N-acylsphingosine glucohydrolase; DE AltName: Full=Glucosylceramidase beta 1 {ECO:0000312|HGNC:HGNC:4177}; DE AltName: Full=Imiglucerase; DE AltName: Full=Lysosomal cholesterol glycosyltransferase {ECO:0000305}; DE AltName: Full=Lysosomal galactosylceramidase {ECO:0000305}; DE EC=3.2.1.46 {ECO:0000269|PubMed:32144204}; DE AltName: Full=Lysosomal glycosylceramidase {ECO:0000305}; DE Flags: Precursor; GN Name=GBA1 {ECO:0000312|HGNC:HGNC:4177}; Synonyms=GBA, GC, GLUC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RC TISSUE=Placenta; RX PubMed=3864160; DOI=10.1073/pnas.82.21.7289; RA Sorge J., West C., Westwood B., Beutler E.; RT "Molecular cloning and nucleotide sequence of human glucocerebrosidase RT cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7289-7293(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANT LEU-298. RC TISSUE=Hepatoma; RX PubMed=3001061; DOI=10.1016/s0021-9258(17)42428-8; RA Tsuji S., Choudary P.V., Martin B.M., Winfield S., Barranger J.A., RA Ginns E.I.; RT "Nucleotide sequence of cDNA containing the complete coding sequence for RT human lysosomal glucocerebrosidase."; RL J. Biol. Chem. 261:50-53(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Liver; RX PubMed=2914709; DOI=10.1016/0888-7543(89)90319-4; RA Horowitz M., Wilder S., Horowitz Z., Reiner O., Gelbart T., Beutler E.; RT "The human glucocerebrosidase gene and pseudogene: structure and RT evolution."; RL Genomics 4:87-96(1989). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Liver; RX PubMed=1572652; DOI=10.1016/0888-7543(92)90311-f; RA Beutler E., West C., Gelbart T.; RT "Polymorphisms in the human glucocerebrosidase gene."; RL Genomics 12:795-800(1992). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND 3), VARIANTS GD ARG-223; RP GLY-230; PRO-235; ARG-241; ILE-252 AND ARG-364, AND VARIANTS GLY-310 AND RP HIS-368. RX PubMed=8294033; DOI=10.1016/0378-1119(93)90497-q; RA Imai K., Nakamura M., Yamada M., Asano A., Yokoyama S., Tsuji S., RA Ginns E.I.; RT "A novel transcript from a pseudogene for human glucocerebrosidase in non- RT Gaucher disease cells."; RL Gene 136:365-368(1993). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9331372; DOI=10.1101/gr.7.10.1020; RA Winfield S.L., Tayebi N., Martin B.M., Ginns E.I., Sidransky E.; RT "Identification of three additional genes contiguous to the RT glucocerebrosidase locus on chromosome 1q21: implications for Gaucher RT disease."; RL Genome Res. 7:1020-1026(1997). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG; 4 AND 5), AND RP VARIANT MET-408. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-11. RX PubMed=3359914; DOI=10.1089/dna.1988.7.107; RA Reiner O., Wigderson M., Horowitz M.; RT "Structural analysis of the human glucocerebrosidase genes."; RL DNA 7:107-116(1988). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45, AND ALTERNATIVE INITIATION. RX PubMed=3687939; RA Sorge J.A., West C., Kuhl W., Treger L., Beutler E.; RT "The human glucocerebrosidase gene has two functional ATG initiator RT codons."; RL Am. J. Hum. Genet. 41:1016-1024(1987). RN [12] RP PROTEIN SEQUENCE OF 40-44, AND CLEAVAGE OF SIGNAL PEPTIDE AFTER GLY-39. RC TISSUE=Placenta; RA Martin B.M., Murray G.J., Coligan J.E., Raum M., Brady R.O., RA Barranger J.A.; RT "Structural studies of human placental glucocerebrosidase."; RL Fed. Proc. 43:1869-1869(1984). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 403-416. RX PubMed=6091633; DOI=10.1016/0006-291x(84)90268-7; RA Ginns E.I., Choudary P.V., Martin B.M., Winfield S., Stubblefield B., RA Mayor J., Merkle-Lehman D., Murray G.J., Bowers L.A., Barranger J.A.; RT "Isolation of cDNA clones for human beta-glucocerebrosidase using the RT lambda gt11 expression system."; RL Biochem. Biophys. Res. Commun. 123:574-580(1984). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 409-462, AND VARIANT GD1 SER-409. RC TISSUE=Skin; RA Tsuji S., Martin B.M., Barranger J.A., Stubblefield B.K., LaMarca M.E., RA Ginns E.I.; RT "Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in RT Ashkenazic and non-Ashkenazic individuals."; RL Proc. Natl. Acad. Sci. U.S.A. 85:2349-2352(1988). RN [15] RP PROTEIN SEQUENCE OF 469-520. RC TISSUE=Placenta; RX PubMed=3456607; DOI=10.1073/pnas.83.6.1660; RA Dinur T., Osiecki K.M., Legler G., Gatt S., Desnick R.J., Grabowski G.A.; RT "Human acid beta-glucosidase: isolation and amino acid sequence of a RT peptide containing the catalytic site."; RL Proc. Natl. Acad. Sci. U.S.A. 83:1660-1664(1986). RN [16] RP TOPOLOGY. RX PubMed=1848227; DOI=10.1016/s0021-9258(19)67728-8; RA Rijnboutt S., Aerts H.M., Geuze H.J., Tager J.M., Strous G.J.; RT "Mannose 6-phosphate-independent membrane association of cathepsin D, RT glucocerebrosidase, and sphingolipid-activating protein in HepG2 cells."; RL J. Biol. Chem. 266:4862-4868(1991). RN [17] RP MUTAGENESIS OF GLU-379, ACTIVE SITE, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=7908905; DOI=10.1016/s0021-9258(19)78077-6; RA Miao S., McCarter J.D., Grace M.E., Grabowski G.A., Aebersold R., RA Withers S.G.; RT "Identification of Glu340 as the active-site nucleophile in human RT glucocerebrosidase by use of electrospray tandem mass spectrometry."; RL J. Biol. Chem. 269:10975-10978(1994). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION. RX PubMed=9201993; DOI=10.1074/jbc.272.27.16862; RA Vaccaro A.M., Tatti M., Ciaffoni F., Salvioli R., Barca A., Scerch C.; RT "Effect of saposins A and C on the enzymatic hydrolysis of liposomal RT glucosylceramide."; RL J. Biol. Chem. 272:16862-16867(1997). RN [19] RP INTERACTION WITH SAPOSIN-C, ACTIVITY REGULATION, AND TOPOLOGY. RX PubMed=10781797; DOI=10.1016/s0014-5793(00)01417-4; RA Salvioli R., Tatti M., Ciaffoni F., Vaccaro A.M.; RT "Further studies on the reconstitution of glucosylceramidase activity by RT Sap C and anionic phospholipids."; RL FEBS Lett. 472:17-21(2000). RN [20] RP GLYCOSYLATION AT ASN-98; ASN-185 AND ASN-309. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [21] RP SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH SCARB2. RX PubMed=18022370; DOI=10.1016/j.cell.2007.10.018; RA Reczek D., Schwake M., Schroder J., Hughes H., Blanz J., Jin X., RA Brondyk W., Van Patten S., Edmunds T., Saftig P.; RT "LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent RT targeting of beta-glucocerebrosidase."; RL Cell 131:770-783(2007). RN [22] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., RA Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [23] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=19279011; DOI=10.1074/jbc.m802790200; RA Kitatani K., Sheldon K., Rajagopalan V., Anelli V., Jenkins R.W., Sun Y., RA Grabowski G.A., Obeid L.M., Hannun Y.A.; RT "Involvement of acid beta-glucosidase 1 in the salvage pathway of ceramide RT formation."; RL J. Biol. Chem. 284:12972-12978(2009). RN [24] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98 AND ASN-309. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [25] RP INTERACTION WITH TCP1, CHARACTERIZATION OF VARIANT GD1 SER-409, AND RP CHARACTERIZATION OF VARIANT GD2 SER-409 AND PRO-483. RX PubMed=21098288; DOI=10.1073/pnas.1014376107; RA Lu J., Chiang J., Iyer R.R., Thompson E., Kaneski C.R., Xu D.S., Yang C., RA Chen M., Hodes R.J., Lonser R.R., Brady R.O., Zhuang Z.; RT "Decreased glucocerebrosidase activity in Gaucher disease parallels RT quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl."; RL Proc. Natl. Acad. Sci. U.S.A. 107:21665-21670(2010). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, SUBSTRATE RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=24211208; DOI=10.1016/j.bbrc.2013.10.145; RA Akiyama H., Kobayashi S., Hirabayashi Y., Murakami-Murofushi K.; RT "Cholesterol glucosylation is catalyzed by transglucosylation reaction of RT beta-glucosidase 1."; RL Biochem. Biophys. Res. Commun. 441:838-843(2013). RN [28] RP INTERACTION WITH SNCA. RX PubMed=23266198; DOI=10.1016/j.ymgme.2012.11.010; RA Yap T.L., Velayati A., Sidransky E., Lee J.C.; RT "Membrane-bound alpha-synuclein interacts with glucocerebrosidase and RT inhibits enzyme activity."; RL Mol. Genet. Metab. 108:56-64(2013). RN [29] RP INTERACTION WITH GRN. RX PubMed=27789271; DOI=10.1016/j.ebiom.2016.10.010; RA Jian J., Tian Q.Y., Hettinghouse A., Zhao S., Liu H., Wei J., Grunig G., RA Zhang W., Setchell K.D.R., Sun Y., Overkleeft H.S., Chan G.L., Liu C.J.; RT "Progranulin Recruits HSP70 to beta-Glucocerebrosidase and Is Therapeutic RT Against Gaucher Disease."; RL EBioMedicine 13:212-224(2016). RN [30] RP FUNCTION. RX PubMed=27378698; DOI=10.1093/hmg/ddw185; RA Magalhaes J., Gegg M.E., Migdalska-Richards A., Doherty M.K., RA Whitfield P.D., Schapira A.H.; RT "Autophagic lysosome reformation dysfunction in glucocerebrosidase RT deficient cells: relevance to Parkinson disease."; RL Hum. Mol. Genet. 25:3432-3445(2016). RN [31] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION. RX PubMed=26724485; DOI=10.1194/jlr.m064923; RA Marques A.R., Mirzaian M., Akiyama H., Wisse P., Ferraz M.J., Gaspar P., RA Ghauharali-van der Vlugt K., Meijer R., Giraldo P., Alfonso P., Irun P., RA Dahl M., Karlsson S., Pavlova E.V., Cox T.M., Scheij S., Verhoek M., RA Ottenhoff R., van Roomen C.P., Pannu N.S., van Eijk M., Dekker N., RA Boot R.G., Overkleeft H.S., Blommaart E., Hirabayashi Y., Aerts J.M.; RT "Glucosylated cholesterol in mammalian cells and tissues: formation and RT degradation by multiple cellular beta-glucosidases."; RL J. Lipid Res. 57:451-463(2016). RN [32] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32144204; DOI=10.1074/jbc.ra119.012502; RA Akiyama H., Ide M., Nagatsuka Y., Sayano T., Nakanishi E., Uemura N., RA Yuyama K., Yamaguchi Y., Kamiguchi H., Takahashi R., Aerts J.M.F.G., RA Greimel P., Hirabayashi Y.; RT "Glucocerebrosidases catalyze a transgalactosylation reaction that yields a RT newly-identified brain sterol metabolite, galactosylated cholesterol."; RL J. Biol. Chem. 295:5257-5277(2020). RN [33] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=33361282; DOI=10.1194/jlr.ra120001043; RA Boer D.E., Mirzaian M., Ferraz M.J., Zwiers K.C., Baks M.V., Hazeu M.D., RA Ottenhoff R., Marques A.R.A., Meijer R., Roos J.C.P., Cox T.M., Boot R.G., RA Pannu N., Overkleeft H.S., Artola M., Aerts J.M.; RT "Human glucocerebrosidase mediates formation of xylosyl-cholesterol by RT beta-xylosidase and transxylosidase reactions."; RL J. Lipid Res. 62:100018-100018(2021). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 40-536, GLYCOSYLATION AT ASN-58, RP AND DISULFIDE BONDS. RX PubMed=12792654; DOI=10.1038/sj.embor.embor873; RA Dvir H., Harel M., McCarthy A.A., Toker L., Silman I., Futerman A.H., RA Sussman J.L.; RT "X-ray structure of human acid-beta-glucosidase, the defective enzyme in RT Gaucher disease."; RL EMBO Rep. 4:704-709(2003). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 40-536 IN COMPLEX WITH SYNTHETIC RP INHIBITOR, AND ACTIVE SITE. RX PubMed=15817452; DOI=10.1074/jbc.m502799200; RA Premkumar L., Sawkar A.R., Boldin-Adamsky S., Toker L., Silman I., RA Kelly J.W., Futerman A.H., Sussman J.L.; RT "X-ray structure of human acid-beta-glucosidase covalently bound to RT conduritol-B-epoxide. Implications for Gaucher disease."; RL J. Biol. Chem. 280:23815-23819(2005). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-536, CATALYTIC ACTIVITY, RP PATHWAY, CHARACTERIZATION OF VARIANTS GD SER-55; GLN-87; ASN-118; LEU-161; RP VAL-162; VAL-166; ASN-200; PHE-213; PHE-224; GLU-232; GLU-237; LEU-298; RP ILE-303; CYS-343; ILE-362; LYS-365; GLY-381; LYS-388; TRP-392; CYS-402; RP SER-409; VAL-410; HIS-419; LYS-421; ARG-429; LEU-433; SER-436; ASN-438; RP HIS-448; VAL-455; PRO-483; PRO-500; CYS-502 AND PRO-502, CHARACTERIZATION RP OF VARIANT GD2 GLN-159, AND MUTAGENESIS OF CYS-43; CYS-57 AND CYS-62. RX PubMed=16293621; DOI=10.1074/jbc.m511110200; RA Liou B., Kazimierczuk A., Zhang M., Scott C.R., Hegde R.S., Grabowski G.A.; RT "Analyses of variant acid beta-glucosidases: effects of Gaucher disease RT mutations."; RL J. Biol. Chem. 281:4242-4253(2006). RN [37] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 40-536, AND GLYCOSYLATION AT RP ASN-58; ASN-98 AND ASN-185. RX PubMed=17139081; DOI=10.1107/s0907444906038303; RA Brumshtein B., Wormald M.R., Silman I., Futerman A.H., Sussman J.L.; RT "Structural comparison of differently glycosylated forms of acid-beta- RT glucosidase, the defective enzyme in Gaucher disease."; RL Acta Crystallogr. D 62:1458-1465(2006). RN [38] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 40-536 IN COMPLEXES WITH RP ISOFAGOMINE, AND SUBCELLULAR LOCATION. RX PubMed=17187079; DOI=10.1038/nchembio850; RA Lieberman R.L., Wustman B.A., Huertas P., Powe A.C. Jr., Pine C.W., RA Khanna R., Schlossmacher M.G., Ringe D., Petsko G.A.; RT "Structure of acid beta-glucosidase with pharmacological chaperone provides RT insight into Gaucher disease."; RL Nat. Chem. Biol. 3:101-107(2007). RN [39] RP REVIEW ON GD VARIANTS. RX PubMed=8118460; DOI=10.1002/humu.1380030102; RA Horowitz M., Zimran A.; RT "Mutations causing Gaucher disease."; RL Hum. Mutat. 3:1-11(1994). RN [40] RP REVIEW ON GD VARIANTS. RX PubMed=8889578; RX DOI=10.1002/(sici)1098-1004(1996)8:3<207::aid-humu2>3.0.co;2-6; RA Beutler E., Gelbart T.; RT "Glucocerebrosidase (Gaucher disease)."; RL Hum. Mutat. 8:207-213(1996). RN [41] RP REVIEW ON GD VARIANTS. RX PubMed=10527671; DOI=10.1006/mgme.1999.2918; RA Tayebi N., Stone D.L., Sidransky E.; RT "Type 2 Gaucher disease: an expanding phenotype."; RL Mol. Genet. Metab. 68:209-219(1999). RN [42] RP VARIANTS GD2 ARG-454 AND PRO-483, AND CHARACTERIZATION OF VARIANTS GD2 RP ARG-454 AND PRO-483. RX PubMed=2464926; RA Wigderson M., Firon N., Horowitz Z., Wilder S., Frishberg Y., Reiner O., RA Horowitz M.; RT "Characterization of mutations in Gaucher patients by cDNA cloning."; RL Am. J. Hum. Genet. 44:365-377(1989). RN [43] RP VARIANTS GD1 LEU-433 AND HIS-448, AND VARIANTS GD3 LEU-433; HIS-448 AND RP VAL-448. RX PubMed=2508065; DOI=10.1093/nar/17.19.7707; RA Theophilus B.D., Latham T., Grabowski G.A., Smith F.I.; RT "Comparison of RNase A, a chemical cleavage and GC-clamped denaturing RT gradient gel electrophoresis for the detection of mutations in exon 9 of RT the human acid beta-glucosidase gene."; RL Nucleic Acids Res. 17:7707-7722(1989). RN [44] RP VARIANT GD TYR-255. RX PubMed=1974409; DOI=10.1111/j.1469-1809.1990.tb00371.x; RA Beutler E., Gelbart T.; RT "Gaucher disease associated with a unique KpnI restriction site: RT identification of the amino-acid substitution."; RL Ann. Hum. Genet. 54:149-153(1990). RN [45] RP VARIANT GD CYS-502, AND CHARACTERIZATION OF VARIANT GD CYS-502. RX PubMed=1972019; DOI=10.1089/dna.1990.9.233; RA Hong C.M., Ohashi T., Yu X.J., Weiler S., Barranger J.A.; RT "Sequence of two alleles responsible for Gaucher disease."; RL DNA Cell Biol. 9:233-241(1990). RN [46] RP VARIANTS GD2 ARG-364 AND GLY-381, AND VARIANT GD1 HIS-448. RX PubMed=2269438; DOI=10.1016/0378-1119(90)90264-r; RA Eyal N., Wilder S., Horowitz M.; RT "Prevalent and rare mutations among Gaucher patients."; RL Gene 96:277-283(1990). RN [47] RP VARIANTS GD1 GLN-196; VAL-348; CYS-351 AND THR-403. RX PubMed=1899336; DOI=10.1089/dna.1991.10.15; RA Latham T.E., Theophilus B.D., Grabowski G.A., Smith F.I.; RT "Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher RT disease patients."; RL DNA Cell Biol. 10:15-21(1991). RN [48] RP VARIANTS GD1 HIS-179; GLN-196 AND LYS-365. RX PubMed=1864608; DOI=10.1007/bf00200914; RA Eyal N., Firon N., Wilder S., Kolodny E.H., Horowitz M.; RT "Three unique base pair changes in a family with Gaucher disease."; RL Hum. Genet. 87:328-332(1991). RN [49] RP VARIANTS GD1 GLN-398 AND CYS-535, AND VARIANT GD3 GLU-464. RX PubMed=1487244; DOI=10.1007/bf00220082; RA Kawame H., Hasegawa Y., Eto Y., Maekawa K.; RT "Rapid identification of mutations in the glucocerebrosidase gene of RT Gaucher disease patients by analysis of single-strand conformation RT polymorphisms."; RL Hum. Genet. 90:294-296(1992). RN [50] RP VARIANTS GD1 ILE-252; LEU-328; ILE-362 AND CYS-502, AND CHARACTERIZATION OF RP VARIANTS GD1 LEU-328; ILE-362 AND CYS-502. RX PubMed=1301953; DOI=10.1002/humu.1380010513; RA He G.S., Grace M.E., Grabowski G.A.; RT "Gaucher disease: four rare alleles encoding F213I, P289L, T323I, and R463C RT in type 1 variants."; RL Hum. Mutat. 1:423-427(1992). RN [51] RP VARIANTS GD HIS-251 AND SER-517, AND VARIANTS GD1 SER-161 AND HIS-535. RX PubMed=8432537; DOI=10.1006/geno.1993.1035; RA Beutler E., Gelbart T., West C.; RT "Identification of six new Gaucher disease mutations."; RL Genomics 15:203-205(1993). RN [52] RP VARIANT GD1 HIS-535. RX PubMed=7916532; DOI=10.1002/ajmg.1320510216; RA Choy F.Y.M., Wei C., Applegarth D.A., McGillivray B.C.; RT "DNA analysis of an uncommon missense mutation in a Gaucher disease patient RT of Jewish-Polish-Russian descent."; RL Am. J. Med. Genet. 51:156-160(1994). RN [53] RP VARIANT GD2 ASN-438. RX PubMed=8112750; DOI=10.1007/bf00210614; RA Beutler E., Gelbart T.; RT "Two new Gaucher disease mutations."; RL Hum. Genet. 93:209-210(1994). RN [54] RP VARIANTS GD SER-409 AND CYS-457. RX PubMed=8076951; DOI=10.1007/bf00208292; RA Tuteja R., Tuteja N., Lilliu F., Bembi B., Galanello R., Cao A., RA Baralle F.E.; RT "Y418C: a novel mutation in exon 9 of the glucocerebrosidase gene of a RT patient with Gaucher disease creates a new Bgl I site."; RL Hum. Genet. 94:314-315(1994). RN [55] RP VARIANTS GD1 SER-409 AND VAL-456. RX PubMed=7915932; DOI=10.1093/hmg/3.5.821; RA Choy F.Y., Wei C., Applegarth D.A., Yong S.L.; RT "A new missense mutation in glucocerebrosidase exon 9 of a non-Jewish RT Caucasian type 1 Gaucher disease patient."; RL Hum. Mol. Genet. 3:821-823(1994). RN [56] RP VARIANT GD2 ARG-483. RX PubMed=7981693; DOI=10.1093/hmg/3.7.1183; RA Uchiyama A., Tomatsu S., Kondo N., Suzuki Y., Shimozawa N., Fukuda S., RA Sukegawa K., Taki N., Inamori H., Orii T.; RT "New Gaucher disease mutations in exon 10: a novel L444R mutation produces RT a new NciI site the same as L444P."; RL Hum. Mol. Genet. 3:1183-1184(1994). RN [57] RP CHARACTERIZATION OF VARIANT GD TYR-255, CHARACTERIZATION OF VARIANTS GD1 RP LEU-328; ILE-362; THR-403; SER-409; LEU-433; HIS-448; PRO-483; PRO-495 AND RP CYS-502, CHARACTERIZATION OF VARIANT GD2 ARG-454, CHARACTERIZATION OF RP VARIANT GD3 VAL-448, AND MUTAGENESIS OF ASP-482 AND ASN-501. RX PubMed=8294487; DOI=10.1016/s0021-9258(17)42166-1; RA Grace M.E., Newman K.M., Scheinker V., Berg-Fussman A., Grabowski G.A.; RT "Analysis of human acid beta-glucosidase by site-directed mutagenesis and RT heterologous expression."; RL J. Biol. Chem. 269:2283-2291(1994). RN [58] RP VARIANTS GD1 ASP-215; THR-221; ARG-241; GLN-296; CYS-324; GLY-417 AND RP ASN-419. RX PubMed=8790604; DOI=10.1007/bf03403534; RA Beutler E., Demina A., Gelbart T.; RT "Glucocerebrosidase mutations in Gaucher disease."; RL Mol. Med. 1:82-92(1994). RN [59] RP VARIANTS GD1 ILE-82 AND TRP-87. RX PubMed=7655857; DOI=10.1006/bcmd.1995.0004; RA Beutler E., Gelbart T., Demina A., Zimran A., LeCoutre P.; RT "Five new Gaucher disease mutations."; RL Blood Cells Mol. Dis. 21:20-24(1995). RN [60] RP VARIANTS GD1 ARG-305; HIS-354 AND ASP-357. RX PubMed=8547070; DOI=10.1111/j.1365-2141.1995.tb05298.x; RA Walley A.J., Ellis I., Harris A.; RT "Three unrelated Gaucher's disease patients with three novel point RT mutations in the glucocerebrosidase gene (P266R, D315H and A318D)."; RL Br. J. Haematol. 91:330-332(1995). RN [61] RP VARIANTS GD SER-409; HIS-448; PRO-483 AND CYS-502. RX PubMed=7627184; DOI=10.1002/humu.1380050406; RA Cormand B., Vilageliu L., Burguera J.M., Balcells S., Gonzalez-Duarte R., RA Grinberg D., Chabas A.; RT "Gaucher disease in Spanish patients: analysis of eight mutations."; RL Hum. Mutat. 5:303-309(1995). RN [62] RP VARIANT GD2 SER-217. RX PubMed=7627192; DOI=10.1002/humu.1380050414; RA Choy F.Y.M., Wei C.; RT "Identification of a new mutation (P178S) in an African-American patient RT with type 2 Gaucher disease."; RL Hum. Mutat. 5:345-347(1995). RN [63] RP VARIANTS GD1 SER-409 AND PRO-483, VARIANTS GD2 HIS-448; PRO-483 AND RP CYS-502, AND VARIANTS GD3 HIS-448 AND PRO-483. RX PubMed=8598642; DOI=10.1007/bf02436006; RA Michelakakis H., Dimitriou E., Van Weely S., Boot R.G., Mavridou I., RA Verhoek M., Aerts J.M.; RT "Characterization of glucocerebrosidase in Greek Gaucher disease patients: RT mutation analysis and biochemical studies."; RL J. Inherit. Metab. Dis. 18:609-615(1995). RN [64] RP VARIANT GD HIS-448. RX PubMed=7475546; DOI=10.1016/s0140-6736(95)91688-1; RA Abrahamov A., Elstein D., Gross-Tsur V., Farber B., Glaser Y., RA Hadas-Halpern I., Ronen S., Tafakjdi M., Horowitz M., Zimran A.; RT "Gaucher's disease variant characterised by progressive calcification of RT heart valves and unique genotype."; RL Lancet 346:1000-1003(1995). RN [65] RP CHARACTERIZATION OF VARIANTS GD1 SER-409; VAL-456 AND HIS-535, AND RP CHARACTERIZATION OF VARIANT GD2 PRO-483. RX PubMed=9240741; RX DOI=10.1002/(sici)1096-8628(19961028)65:3<184::aid-ajmg3>3.0.co;2-q; RA Choy F.Y., Wei C., Levin D.; RT "Gaucher disease: functional expression of the normal glucocerebrosidase RT and Gaucher T1366G and G1604A alleles in Baculovirus-transfected Spodoptera RT frugiperda cells."; RL Am. J. Med. Genet. 65:184-189(1996). RN [66] RP VARIANTS GD SER-409; LEU-426; LEU-433 AND PRO-483. RX PubMed=8937765; DOI=10.1111/j.1399-0004.1996.tb02352.x; RA Morar B., Lane A.B.; RT "The molecular characterization of Gaucher disease in South Africa."; RL Clin. Genet. 50:78-84(1996). RN [67] RP VARIANTS GD LEU-54; GLU-85 AND SER-227. RX PubMed=8829654; RX DOI=10.1002/(sici)1098-1004(1996)7:3<214::aid-humu5>3.0.co;2-a; RA Kim J.-W., Liou B.B., Lai M.-Y., Ponce E., Grabowski G.A.; RT "Gaucher disease: identification of three new mutations in the Korean and RT Chinese (Taiwanese) populations."; RL Hum. Mutat. 7:214-218(1996). RN [68] RP VARIANTS GD HIS-352 AND GLN-398. RX PubMed=8829663; RX DOI=10.1002/(sici)1098-1004(1996)7:3<272::aid-humu14>3.0.co;2-#; RA Cormand B., Vilageliu L., Balcells S., Gonzalez-Duatre R., Chabas A., RA Grinberg D.; RT "Two novel (1098insA and Y313H) and one rare (R359Q) mutations detected in RT exon 8 of the beta-glucocerebrosidase gene in Gaucher's disease patients."; RL Hum. Mutat. 7:272-274(1996). RN [69] RP VARIANT GD1 THR-435. RX PubMed=8889591; RX DOI=10.1002/(sici)1098-1004(1996)8:3<280::aid-humu15>3.0.co;2-z; RA Amaral O., Pinto E., Fortuna M., Lacerda L., Sa Miranda M.C.; RT "Type 1 Gaucher disease: identification of N396T and prevalence of RT glucocerebrosidase mutations in the Portuguese."; RL Hum. Mutat. 8:280-281(1996). RN [70] RP VARIANTS GD3 LEU-437 AND ILE-530. RX PubMed=8780099; DOI=10.1212/wnl.46.4.1102; RA Seeman P.J.V., Finckh U., Hoeppner J., Lakner V., Liebisch I., Grau G., RA Rolfs A.; RT "Two new missense mutations in a non-Jewish Caucasian family with type 3 RT Gaucher disease."; RL Neurology 46:1102-1107(1996). RN [71] RP VARIANTS GD LEU-414 AND THR-441. RX PubMed=9182788; RX DOI=10.1002/(sici)1096-8628(19970627)70:4<437::aid-ajmg19>3.0.co;2-i; RA Cormand B., Grinberg D., Gort L., Fiumara A., Barone R., Vilageliu L., RA Chabas A.; RT "Two new mild homozygous mutations in Gaucher disease patients: clinical RT signs and biochemical analyses."; RL Am. J. Med. Genet. 70:437-443(1997). RN [72] RP VARIANTS GD VAL-76; GLU-85; TRP-87; TRP-159; SER-227; ILE-252 AND PRO-483. RX PubMed=9217217; RX DOI=10.1002/(sici)1096-8628(19970808)71:2<172::aid-ajmg10>3.0.co;2-b; RA Choy F.Y.M., Humphries M.L., Shi H.; RT "Identification of two novel and four uncommon missense mutations among RT Chinese Gaucher disease patients."; RL Am. J. Med. Genet. 71:172-178(1997). RN [73] RP VARIANT GD1 TRP-87. RX PubMed=9295080; RX DOI=10.1002/(sici)1096-8628(19971003)72:1<77::aid-ajmg16>3.0.co;2-r; RA Rockah R., Narinsky R., Hatskelzon L., Frisch A.; RT "Type I Gaucher disease due to homozygosity for the 259T mutation in a RT Bedouin patient."; RL Am. J. Med. Genet. 72:77-78(1997). RN [74] RP VARIANT GD2 LYS-501. RX PubMed=9279145; DOI=10.1136/adc.77.1.17; RA Hatton C.E., Cooper A., Whitehouse C., Wraith J.E.; RT "Mutation analysis in 46 British and Irish patients with Gaucher's RT disease."; RL Arch. Dis. Child. 77:17-22(1997). RN [75] RP VARIANTS GD1 TRP-87; GLU-234; ASN-310; LEU-391 AND SER-409, VARIANTS GD2 RP ARG-241 AND ILE-252, CHARACTERIZATION OF VARIANTS GD1 TRP-87; GLU-234; RP ASN-310; LEU-391 AND SER-409, AND CHARACTERIZATION OF VARIANT GD2 ARG-241. RX PubMed=9153297; DOI=10.1172/jci119437; RA Grace M.E., Desnick R.J., Pastores G.M.; RT "Identification and expression of acid beta-glucosidase mutations causing RT severe type 1 and neurologic type 2 Gaucher disease in non-Jewish RT patients."; RL J. Clin. Invest. 99:2530-2537(1997). RN [76] RP VARIANTS GD VAL-228; ILE-252; GLY-405; HIS-448; GLN-452; PRO-483 AND RP CYS-535. RX PubMed=9061570; DOI=10.1023/a:1005313724361; RA Ida H., Rennert O.M., Kawame H., Maekawa K., Eto Y.; RT "Mutation prevalence among 47 unrelated Japanese patients with Gaucher RT disease: identification of four novel mutations."; RL J. Inherit. Metab. Dis. 20:67-73(1997). RN [77] RP VARIANT GD3C HIS-448. RX PubMed=9040001; DOI=10.1136/jmg.34.2.175; RA Uyama E., Uchino M., Ida H., Eto Y., Owada M.; RT "D409H/D409H genotype in Gaucher-like disease."; RL J. Med. Genet. 34:175-175(1997). RN [78] RP VARIANTS GD LEU-198; THR-380; ASN-405 AND ARG-432, AND VARIANT GD2 LEU-146. RX PubMed=9554454; DOI=10.1159/000040815; RA Demina A., Beutler E.; RT "Six new Gaucher disease mutations."; RL Acta Haematol. 99:80-82(1998). RN [79] RP VARIANTS GD1 TRP-87; THR-158; TRP-159; PRO-209; LYS-227; PRO-276; ILE-342; RP PRO-363; SER-409; SER-416; PRO-483; PRO-485 AND CYS-502, AND VARIANTS GD3 RP LEU-433 AND PRO-483. RX PubMed=9683600; DOI=10.1086/301969; RA Germain D.P., Puech J.-P., Caillaud C., Kahn A., Poenaru L.; RT "Exhaustive screening of the acid beta-glucosidase gene, by fluorescence- RT assisted mismatch analysis using universal primers: mutation profile and RT genotype/phenotype correlations in Gaucher disease."; RL Am. J. Hum. Genet. 63:415-427(1998). RN [80] RP VARIANT GD2 TYR-513. RX PubMed=9637431; RX DOI=10.1002/(sici)1096-8628(19980616)78:1<92::aid-ajmg19>3.3.co;2-8; RA Choy F.Y.M., Humphries M.L., Ben-Yoseph Y.; RT "Gaucher type 2 disease: identification of a novel transversion mutation in RT a French-Irish patient."; RL Am. J. Med. Genet. 78:92-93(1998). RN [81] RP VARIANTS GD1 TRP-87; TRP-159; SER-200; ARG-241; ASP-304; CYS-324; SER-409; RP ASN-438; ILE-450 AND PRO-483, AND VARIANT GD2 HIS-448. RX PubMed=9856561; RX DOI=10.1002/(sici)1096-8628(19981204)80:4<343::aid-ajmg8>3.0.co;2-w; RA Cormand B., Harboe T.L., Gort L., Campoy C., Blanco M., Chamoles N., RA Chabas A., Vilageliu L., Grinberg D.; RT "Mutation analysis of Gaucher disease patients from Argentina: high RT prevalence of the RecNciI mutation."; RL Am. J. Med. Genet. 80:343-351(1998). RN [82] RP VARIANTS GD. RX PubMed=9516376; DOI=10.1006/bcmd.1998.0165; RA Beutler E., Gelbart T.; RT "Hematologically important mutations: Gaucher disease."; RL Blood Cells Mol. Dis. 24:2-8(1998). RN [83] RP VARIANTS GD2 LYS-80; CYS-170 AND PRO-483. RX PubMed=9851895; DOI=10.1006/bcmd.1998.0210; RA Sinclair G., Choy F.Y.M., Humphries L.; RT "A novel complex allele and two new point mutations in type 2 (acute RT neuronopathic) Gaucher disease."; RL Blood Cells Mol. Dis. 24:420-427(1998). RN [84] RP VARIANT GD GLY-392. RX PubMed=9650766; DOI=10.1111/j.1399-0004.1998.tb02697.x; RA Parenti G., Filocamo M., Titomanlio L., Rizzolo G., Silvestro E., RA Perretti A., Gatti R., Andria G.; RT "A novel mutation of the beta-glucocerebrosidase gene associated with RT neurologic manifestations in three sibs."; RL Clin. Genet. 53:281-285(1998). RN [85] RP VARIANTS GD1 GLU-152; PRO-173; LEU-430 AND HIS-451, AND VARIANTS GD2 RP GLU-428 AND ILE-431. RX PubMed=9554746; RX DOI=10.1002/(sici)1098-1004(1998)11:4<295::aid-humu7>3.0.co;2-6; RA Cormand B., Grinberg D., Gort L., Chabas A., Vilageliu L.; RT "Molecular analysis and clinical findings in the Spanish Gaucher disease RT population: putative haplotype of the N370S ancestral chromosome."; RL Hum. Mutat. 11:295-305(1998). RN [86] RP VARIANTS GD1 GLY-230 AND SER-409. RX PubMed=10206680; RA Choy F.Y.M., Humphries M.L., Ben-Yoseph Y.; RT "A novel mutation (V191G) in a German-British type 1 Gaucher disease RT patient."; RL Hum. Mutat. 11:411-412(1998). RN [87] RP VARIANTS GD1 SER-409 AND LEU-440. RX PubMed=10340647; RX DOI=10.1002/(sici)1096-8628(19990604)84:4<334::aid-ajmg5>3.3.co;2-g; RA Wasserstein M.P., Martignetti J.A., Zeitlin R., Lumerman H., Solomon M., RA Grace M.E., Desnick R.J.; RT "Type 1 Gaucher disease presenting with extensive mandibular lytic lesions: RT identification and expression of a novel acid beta-glucosidase mutation."; RL Am. J. Med. Genet. 84:334-339(1999). RN [88] RP VARIANT GD1 CYS-244, VARIANTS GD2 ILE-252 AND PRO-483, AND VARIANTS GD3 RP ARG-241; HIS-448 AND PRO-483. RX PubMed=10360404; RX DOI=10.1002/(sici)1096-8628(19990611)84:5<484::aid-ajmg14>3.0.co;2-w; RA Choy F.Y.M., Wong K., Shi H.P.; RT "Glucocerebrosidase mutations among Chinese neuronopathic and non- RT neuronopathic Gaucher disease patients."; RL Am. J. Med. Genet. 84:484-486(1999). RN [89] RP VARIANTS GD. RX PubMed=10744424; RA Hodanov K., Hrebicek M., Cervenkov M., Mrzov L., Veprekov L., Zemen J.; RT "Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher RT patients: mutation profile and description of six novel mutant alleles."; RL Blood Cells Mol. Dis. 25:287-298(1999). RN [90] RP VARIANTS GDPL ARG-350 AND PHE-437. RX PubMed=10352942; DOI=10.1038/sj.ejhg.5200315; RA Stone D.L., van Diggelen O.P., de Klerk J.B.C., Gaillard J.L.J., RA Niermeijer M.F., Willemsen R., Tayebi N., Sidransky E.; RT "Is the perinatal lethal form of Gaucher disease more common than classic RT type 2 Gaucher disease?"; RL Eur. J. Hum. Genet. 7:505-509(1999). RN [91] RP VARIANTS GD PRO-173; TRP-234; SER-409; SER-416; HIS-448 AND PRO-483. RX PubMed=10447266; RX DOI=10.1002/(sici)1098-1004(1999)14:1<88::aid-humu16>3.0.co;2-e; RA Sarria A.J., Giraldo P., Perez-Calvo J.I., Pocovi M.; RT "Detection of three rare (G377S, T134P and 1451delAC), and two novel RT mutations (G195W and Rec[1263del55;1342G>C]] in Spanish Gaucher disease RT patients."; RL Hum. Mutat. 14:88-88(1999). RN [92] RP VARIANTS GD1 TRP-87; ASN-118; THR-129; ASP-156; GLN-159; TRP-159; LEU-170; RP ILE-173; CYS-209; PRO-209; SER-227; PRO-235; ARG-241; ILE-252; GLN-296; RP CYS-324; LYS-365; THR-380; MET-408; SER-409; SER-416; LEU-433; TYR-438; RP HIS-448; PRO-483 AND CYS-502, VARIANT GD2 GLN-159, AND VARIANTS GD3 RP THR-229; HIS-448; PRO-483 AND CYS-502. RX PubMed=10796875; DOI=10.1086/302925; RA Koprivica V., Stone D.L., Park J.K., Callahan M., Frisch A., Cohen I.J., RA Tayebi N., Sidransky E.; RT "Analysis and classification of 304 mutant alleles in patients with type 1 RT and type 3 Gaucher disease."; RL Am. J. Hum. Genet. 66:1777-1786(2000). RN [93] RP VARIANTS GD2 LEU-170; LYS-227; GLU-229; PRO-235; GLN-294; GLN-296; LEU-298; RP HIS-324 AND CYS-343. RX PubMed=10649495; RX DOI=10.1002/(sici)1098-1004(200002)15:2<181::aid-humu7>3.0.co;2-s; RA Stone D.L., Tayebi N., Orvisky E., Stubblefield B., Madike V., RA Sidransky E.; RT "Glucocerebrosidase gene mutations in patients with type 2 Gaucher RT disease."; RL Hum. Mutat. 15:181-188(2000). RN [94] RP VARIANTS GD2 ARG-223 AND PRO-483. RX PubMed=10679038; DOI=10.1007/s100240050023; RA Choy F.Y., Wong K., Vallance H.D., Baldwin V.; RT "Novel point mutation (W184R) in neonatal type 2 Gaucher disease."; RL Pediatr. Dev. Pathol. 3:180-183(2000). RN [95] RP VARIANTS GD SER-55 AND HIS-448. RX PubMed=11992489; DOI=10.1002/ajmg.10385; RA Bodamer O.A.F., Church H.J., Cooper A., Wraith J.E., Scott C.R., RA Scaglia F.; RT "Variant Gaucher disease characterized by dysmorphic features, absence of RT cardiovascular involvement, laryngospasm, and compound heterozygosity for a RT novel mutation (D409H/C16S)."; RL Am. J. Med. Genet. 109:328-331(2002). RN [96] RP VARIANT LYS-365. RX PubMed=11903352; DOI=10.1034/j.1399-0004.2002.610106.x; RA Park J.K., Tayebi N., Stubblefield B.K., LaMarca M.E., MacKenzie J.J., RA Stone D.L., Sidransky E.; RT "The E326K mutation and Gaucher disease: mutation or polymorphism?"; RL Clin. Genet. 61:32-34(2002). RN [97] RP VARIANT GD GLU-175, VARIANT GDPL LEU-290, VARIANTS GD1 PRO-201 AND SER-409, RP VARIANT GD2 GLU-237, AND VARIANTS GD3 CYS-244; SER-416; PHE-441 AND RP HIS-448. RX PubMed=11933202; DOI=10.1002/humu.9024; RA Orvisky E., Park J.K., Parker A., Walker J.M., Martin B.M., RA Stubblefield B.K., Uyama E., Tayebi N., Sidransky E.; RT "The identification of eight novel glucocerebrosidase (GBA) mutations in RT patients with Gaucher disease."; RL Hum. Mutat. 19:458-459(2002). RN [98] RP VARIANTS GD1 THR-198; CYS-209; PRO-209; ARG-241; ILE-252; CYS-324; HIS-324; RP CYS-351; ASN-438; HIS-448; CYS-457; PRO-485 AND ARG-490, VARIANTS GD2 RP CYS-170; PRO-235; ARG-241; ARG-270 AND ILE-400, AND VARIANTS GD3 LEU-146; RP SER-227; ARG-241; ILE-252; CYS-324; GLY-392 AND HIS-448. RX PubMed=12204005; DOI=10.1002/humu.9058; RA Filocamo M., Mazzotti R., Stroppiano M., Seri M., Giona F., Parenti G., RA Regis S., Corsolini F., Zoboli S., Gatti R.; RT "Analysis of the glucocerebrosidase gene and mutation profile in 144 RT Italian Gaucher patients."; RL Hum. Mutat. 20:234-235(2002). RN [99] RP VARIANT MET-408. RX PubMed=12694238; DOI=10.1034/j.1399-0004.2003.00055.x; RA Walker J.M., Lwin A., Tayebi N., LaMarca M.E., Orvisky E., Sidransky E.; RT "Glucocerebrosidase mutation T369M appears to be another polymorphism."; RL Clin. Genet. 63:237-238(2003). RN [100] RP POSSIBLE INVOLVEMENT IN PARKINSON DISEASE. RX PubMed=12847165; DOI=10.1212/01.wnl.0000072482.70963.d7; RA Bembi B., Zambito Marsala S., Sidransky E., Ciana G., Carrozzi M., RA Zorzon M., Martini C., Gioulis M., Pittis M.G., Capus L.; RT "Gaucher's disease with Parkinson's disease: clinical and pathological RT aspects."; RL Neurology 61:99-101(2003). RN [101] RP VARIANT GD SER-55. RX PubMed=15292921; DOI=10.1038/sj.ejhg.5201251; RA Church H.J., Cooper A., Stewart F., Thornton C.M., Wraith J.E.; RT "Homozygous loss of a cysteine residue in the glucocerebrosidase gene RT results in Gaucher's disease with a hydropic phenotype."; RL Eur. J. Hum. Genet. 12:975-978(2004). RN [102] RP VARIANTS GD2 GLN-294 AND HIS-448. RX PubMed=15690354; DOI=10.1002/ajmg.a.30316; RA Filocamo M., Grossi S., Stroppiano M., Tortori-Donati P., Regis S., RA Allegri A., Di Rocco M.; RT "Homozygosity for a non-pseudogene complex glucocerebrosidase allele as RT cause of an atypical neuronopathic form of Gaucher disease."; RL Am. J. Med. Genet. A 134A:95-96(2005). RN [103] RP CHARACTERIZATION OF VARIANT GD SER-409. RX PubMed=15826241; DOI=10.1042/bj20050325; RA Salvioli R., Tatti M., Scarpa S., Moavero S.M., Ciaffoni F., Felicetti F., RA Kaneski C.R., Brady R.O., Vaccaro A.M.; RT "The N370S (Asn370->Ser) mutation affects the capacity of RT glucosylceramidase to interact with anionic phospholipid-containing RT membranes and saposin C."; RL Biochem. J. 390:95-103(2005). RN [104] RP CHARACTERIZATION OF VARIANTS GD HIS-179 AND GLN-196, CATALYTIC ACTIVITY, RP AND FUNCTION. RX PubMed=15916907; DOI=10.1016/j.bcmd.2005.03.006; RA Ron I., Dagan A., Gatt S., Pasmanik-Chor M., Horowitz M.; RT "Use of fluorescent substrates for characterization of Gaucher disease RT mutations."; RL Blood Cells Mol. Dis. 35:57-65(2005). RN [105] RP VARIANTS GD1 ASN-63; SER-158; TRP-159; CYS-170; LEU-221; GLU-230; ARG-241; RP CYS-324; SER-409; ASN-438; LEU-440; HIS-448; CYS-457; ASP-460; PRO-483 AND RP ARG-490, AND CHARACTERIZATION OF VARIANTS GD1 ASN-63; SER-158; LEU-221; RP GLU-230; ASP-460 AND ARG-490. RX PubMed=15605411; DOI=10.1002/humu.9301; RA Miocic S., Filocamo M., Dominissini S., Montalvo A.L., Vlahovicek K., RA Deganuto M., Mazzotti R., Cariati R., Bembi B., Pittis M.G.; RT "Identification and functional characterization of five novel mutant RT alleles in 58 Italian patients with Gaucher disease type 1."; RL Hum. Mutat. 25:100-100(2005). RN [106] RP POSSIBLE INVOLVEMENT IN PARKINSON DISEASE. RX PubMed=16148263; DOI=10.1212/01.wnl.0000176987.47875.28; RA Aharon-Peretz J., Badarny S., Rosenbaum H., Gershoni-Baruch R.; RT "Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype- RT genotype correlation."; RL Neurology 65:1460-1461(2005). RN [107] RP INVOLVEMENT OF VARIANT GD PRO-483 IN SUSCEPTIBILITY TO PARKINSON DISEASE. RX PubMed=17620502; DOI=10.1001/archneur.64.7.1056; RA Tan E.K., Tong J., Fook-Chong S., Yih Y., Wong M.C., Pavanni R., Zhao Y.; RT "Glucocerebrosidase mutations and risk of Parkinson disease in Chinese RT patients."; RL Arch. Neurol. 64:1056-1058(2007). RN [108] RP INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO RP PARKINSON DISEASE. RX PubMed=18332251; DOI=10.1001/archneurol.2007.68; RA Mata I.F., Samii A., Schneer S.H., Roberts J.W., Griffith A., Leis B.C., RA Schellenberg G.D., Sidransky E., Bird T.D., Leverenz J.B., Tsuang D., RA Zabetian C.P.; RT "Glucocerebrosidase gene mutations: a risk factor for Lewy body RT disorders."; RL Arch. Neurol. 65:379-382(2008). RN [109] RP INVOLVEMENT IN PARKINSON DISEASE, AND VARIANTS GLU-46; CYS-170; GLU-232; RP GLN-296; SER-409; ALA-419; HIS-448; ASN-482; PRO-483; PRO-495; LEU-497 AND RP CYS-502. RX PubMed=19286695; DOI=10.1093/brain/awp044; RA Neumann J., Bras J., Deas E., O'Sullivan S.S., Parkkinen L., Lachmann R.H., RA Li A., Holton J., Guerreiro R., Paudel R., Segarane B., Singleton A., RA Lees A., Hardy J., Houlden H., Revesz T., Wood N.W.; RT "Glucocerebrosidase mutations in clinical and pathologically proven RT Parkinson's disease."; RL Brain 132:1783-1794(2009). RN [110] RP INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO RP PARKINSON DISEASE. RX PubMed=19846850; DOI=10.1056/nejmoa0901281; RA Sidransky E., Nalls M.A., Aasly J.O., Aharon-Peretz J., Annesi G., RA Barbosa E.R., Bar-Shira A., Berg D., Bras J., Brice A., Chen C.M., RA Clark L.N., Condroyer C., De Marco E.V., Durr A., Eblan M.J., Fahn S., RA Farrer M.J., Fung H.C., Gan-Or Z., Gasser T., Gershoni-Baruch R., RA Giladi N., Griffith A., Gurevich T., Januario C., Kropp P., Lang A.E., RA Lee-Chen G.J., Lesage S., Marder K., Mata I.F., Mirelman A., Mitsui J., RA Mizuta I., Nicoletti G., Oliveira C., Ottman R., Orr-Urtreger A., RA Pereira L.V., Quattrone A., Rogaeva E., Rolfs A., Rosenbaum H., RA Rozenberg R., Samii A., Samaddar T., Schulte C., Sharma M., Singleton A., RA Spitz M., Tan E.K., Tayebi N., Toda T., Troiano A.R., Tsuji S., RA Wittstock M., Wolfsberg T.G., Wu Y.R., Zabetian C.P., Zhao Y., RA Ziegler S.G.; RT "Multicenter analysis of glucocerebrosidase mutations in Parkinson's RT disease."; RL N. Engl. J. Med. 361:1651-1661(2009). RN [111] RP VARIANTS GD1 VAL-289; GLY-301 AND GLU-486. RX PubMed=22658918; DOI=10.1016/j.ymgme.2012.05.006; RA Duran R., McNeill A., Mehta A., Hughes D., Cox T., Deegan P., RA Schapira A.H., Hardy J.; RT "Novel pathogenic mutations in the glucocerebrosidase locus."; RL Mol. Genet. Metab. 106:495-497(2012). RN [112] RP VARIANTS GD1 LEU-266 AND SER-347. RX PubMed=24577513; DOI=10.1007/s00277-014-2036-x; RA Machaczka M., Klimkowska M.; RT "Novel heterozygous c.798C>G and c.1040T>G mutations in the GBA1 gene are RT associated with a severe phenotype of Gaucher disease type 1."; RL Ann. Hematol. 93:1787-1789(2014). RN [113] RP VARIANTS GD1 SER-198; THR-284; SER-351; LYS-365; ARG-405; ASN-419 AND RP CYS-420, CHARACTERIZATION OF VARIANTS GD1 SER-198; THR-284; SER-351; RP LYS-365; ARG-405; SER-409; ASN-419 AND CYS-420, VARIANTS GD2 ILE-227 AND RP LYS-274, CHARACTERIZATION OF VARIANTS GD2 ILE-227 AND LYS-274, VARIANTS GD3 RP SER-227 AND ARG-304, AND CHARACTERIZATION OF VARIANTS GD3 SER-227 AND RP ARG-304. RX PubMed=24022302; DOI=10.1038/ejhg.2013.182; RA Malini E., Grossi S., Deganuto M., Rosano C., Parini R., Dominisini S., RA Cariati R., Zampieri S., Bembi B., Filocamo M., Dardis A.; RT "Functional analysis of 11 novel GBA alleles."; RL Eur. J. Hum. Genet. 22:511-516(2014). RN [114] RP VARIANT GD1 TRP-62. RX PubMed=24434810; DOI=10.1016/j.gene.2014.01.015; RA Jack A., Amato D., Morris G., Choy F.Y.; RT "Two novel mutations in glucocerebrosidase, C23W and IVS7-1 G>A, identified RT in Type 1 Gaucher patients heterozygous for N370S."; RL Gene 538:84-87(2014). RN [115] RP VARIANT PRO-363. RX PubMed=26528954; DOI=10.1002/ana.24553; RG International Parkinsonism Genetics Network; RA Olgiati S., Quadri M., Fang M., Rood J.P., Saute J.A., Chien H.F., RA Bouwkamp C.G., Graafland J., Minneboo M., Breedveld G.J., Zhang J., RA Verheijen F.W., Boon A.J., Kievit A.J., Jardim L.B., Mandemakers W., RA Barbosa E.R., Rieder C.R., Leenders K.L., Wang J., Bonifati V.; RT "DNAJC6 mutations associated with early-onset Parkinson's disease."; RL Ann. Neurol. 79:244-256(2016). RN [116] RP VARIANT GD2 ARG-350, AND VARIANTS GD1 SER-409; SER-416; ARG-483; PRO-483 RP AND PRO-495. RX PubMed=27825739; DOI=10.1016/j.bcmd.2016.10.013; RA Basgalupp S.P., Siebert M., Vairo F.P.E., Chami A.M., Pinto L.L.C., RA Carvalho G.D.S., Schwartz I.V.D.; RT "Use of a multiplex ligation-dependent probe amplification method for the RT detection of deletions/duplications in the GBA1 gene in Gaucher disease RT patients."; RL Blood Cells Mol. Dis. 68:17-20(2018). RN [117] RP VARIANTS GD1 GLN-87; LEU-120; HIS-155; TRP-159; SER-174; PRO-214; ARG-223; RP ARG-241; ILE-252; ILE-270; GLN-294; ASN-322; VAL-348; ARG-350; SER-409; RP HIS-448; PRO-483; TYR-501; LYS-521 AND CYS-535, VARIANTS GD2 TRP-159; RP ARG-241; GLN-294; HIS-448 AND PRO-483, AND VARIANTS GD3 CYS-147; GLN-294; RP HIS-448 AND PRO-483. RX PubMed=32547927; DOI=10.1016/j.ymgmr.2020.100614; RA Dimitriou E., Moraitou M., Cozar M., Serra-Vinardell J., Vilageliu L., RA Grinberg D., Mavridou I., Michelakakis H.; RT "Gaucher disease: Biochemical and molecular findings in 141 patients RT diagnosed in Greece."; RL Mol. Genet. Metab. Rep. 24:100614-100614(2020). RN [118] RP CHARACTERIZATION OF VARIANT GD3 VAL-448. RX PubMed=34106956; DOI=10.1371/journal.pone.0252325; RA Polinski N.K., Martinez T.N., Gorodinsky A., Gareus R., Sasner M., RA Herberth M., Switzer R., Ahmad S.O., Cosden M., Kandebo M., Drolet R.E., RA Buckett P.D., Shan W., Chen Y., Pellegrino L.J., Ellsworth G.D., RA Dungan L.B., Hirst W.D., Clark S.W., Dave K.D.; RT "Decreased glucocerebrosidase activity and substrate accumulation of RT glycosphingolipids in a novel GBA1 D409V knock-in mouse model."; RL PLoS ONE 16:e0252325-e0252325(2021). RN [119] RP VARIANTS GD1 LEU-414 AND HIS-448. RX PubMed=36776904; DOI=10.3389/fped.2023.1092645; RA Liu Q., Shen Z., Pan H., Ma S., Xiong F., He F.; RT "The molecular mechanism of Gaucher disease caused by compound heterozygous RT mutations in GBA1 gene."; RL Front. Pediatr. 11:1092645-1092645(2023). CC -!- FUNCTION: Glucosylceramidase that catalyzes, within the lysosomal CC compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta- CC D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as CC N-acylsphing-4-enine) and glucose (PubMed:9201993, PubMed:24211208, CC PubMed:15916907, PubMed:32144204). Plays a central role in the CC degradation of complex lipids and the turnover of cellular membranes CC (PubMed:27378698). Through the production of ceramides, participates in CC the PKC-activated salvage pathway of ceramide formation CC (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through CC a transglucosylation reaction where glucose is transferred from GlcCer CC to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204). CC GlcCer containing mono-unsaturated fatty acids (such as beta-D- CC glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose CC donors for cholesterol glucosylation when compared with GlcCer CC containing same chain length of saturated fatty acids (such as beta-D- CC glucosyl-N-octadecanoyl-sphing-4-enine) (PubMed:24211208). Under CC specific conditions, may alternatively catalyze the reverse reaction, CC transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide CC (PubMed:26724485) (Probable). Can also hydrolyze cholesteryl 3-beta-D- CC glucoside producing glucose and cholesterol (PubMed:24211208, CC PubMed:26724485). Catalyzes the hydrolysis of CC galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N- CC acylsphing-4-enine), as well as the transfer of galactose between CC GalCers and cholesterol in vitro, but with lower activity than with CC GlcCers (PubMed:32144204). Contrary to GlcCer and GalCer, CC xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4- CC enine) is not a good substrate for hydrolysis, however it is a good CC xylose donor for transxylosylation activity to form cholesteryl 3-beta- CC D-xyloside (PubMed:33361282). {ECO:0000269|PubMed:15916907, CC ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208, CC ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:27378698, CC ECO:0000269|PubMed:32144204, ECO:0000269|PubMed:33361282, CC ECO:0000269|PubMed:9201993, ECO:0000305|PubMed:32144204}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + H2O = an N- CC acylsphing-4-enine + D-glucose; Xref=Rhea:RHEA:13269, CC ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, ChEBI:CHEBI:22801, CC ChEBI:CHEBI:52639; EC=3.2.1.45; CC Evidence={ECO:0000269|PubMed:15916907, ECO:0000269|PubMed:16293621, CC ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204, CC ECO:0000269|PubMed:9201993}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270; CC Evidence={ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an CC N-acylsphing-4-enine + D-galactose; Xref=Rhea:RHEA:14297, CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:18390, CC ChEBI:CHEBI:52639; EC=3.2.1.46; CC Evidence={ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298; CC Evidence={ECO:0000305|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cholesteryl 3-beta-D-glucoside + H2O = cholesterol + D- CC glucose; Xref=Rhea:RHEA:11956, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495; CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:33361282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957; CC Evidence={ECO:0000269|PubMed:33361282, ECO:0000305|PubMed:24211208}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + cholesterol CC = an N-acylsphing-4-enine + cholesteryl 3-beta-D-glucoside; CC Xref=Rhea:RHEA:58264, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, CC ChEBI:CHEBI:22801, ChEBI:CHEBI:52639; CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, CC ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265; CC Evidence={ECO:0000269|PubMed:32144204, ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266; CC Evidence={ECO:0000305|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4E-enine + CC cholesterol = cholesteryl 3-beta-D-glucoside + N-(9Z-octadecenoyl)- CC sphing-4-enine; Xref=Rhea:RHEA:58324, ChEBI:CHEBI:16113, CC ChEBI:CHEBI:17495, ChEBI:CHEBI:77996, ChEBI:CHEBI:139140; CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58325; CC Evidence={ECO:0000269|PubMed:32144204, ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58326; CC Evidence={ECO:0000305|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-(1<->1')-N-hexadecanoylsphing-4-enine + CC cholesterol = cholesteryl 3-beta-D-glucoside + N-hexadecanoylsphing- CC 4-enine; Xref=Rhea:RHEA:58316, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, CC ChEBI:CHEBI:72959, ChEBI:CHEBI:84716; CC Evidence={ECO:0000269|PubMed:24211208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58317; CC Evidence={ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58318; CC Evidence={ECO:0000305}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-N-octanoylsphing-4E-enine + cholesterol = CC cholesteryl 3-beta-D-glucoside + N-octanoylsphing-4-enine; CC Xref=Rhea:RHEA:70303, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, CC ChEBI:CHEBI:45815, ChEBI:CHEBI:65222; CC Evidence={ECO:0000269|PubMed:24211208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70304; CC Evidence={ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70305; CC Evidence={ECO:0000305}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-N-dodecanoylsphing-4-enine + cholesterol = CC cholesteryl 3-beta-D-glucoside + N-dodecanoylsphing-4-enine; CC Xref=Rhea:RHEA:70307, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, CC ChEBI:CHEBI:72956, ChEBI:CHEBI:76297; CC Evidence={ECO:0000269|PubMed:24211208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70308; CC Evidence={ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70309; CC Evidence={ECO:0000305}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-(1<->1)-N-octadecanoylsphing-4-enine + CC cholesterol = cholesteryl 3-beta-D-glucoside + N-octadecanoylsphing- CC 4-enine; Xref=Rhea:RHEA:70311, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, CC ChEBI:CHEBI:72961, ChEBI:CHEBI:84719; CC Evidence={ECO:0000269|PubMed:24211208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70312; CC Evidence={ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70313; CC Evidence={ECO:0000305}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-glucosyl-(1<->1')-N-(15Z-tetracosenoyl)-sphing-4-enine CC + cholesterol = cholesteryl 3-beta-D-glucoside + N-(15Z- CC tetracosenoyl)-sphing-4-enine; Xref=Rhea:RHEA:70315, CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, ChEBI:CHEBI:74450, CC ChEBI:CHEBI:76302; Evidence={ECO:0000269|PubMed:24211208}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70316; CC Evidence={ECO:0000305|PubMed:24211208}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70317; CC Evidence={ECO:0000305}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + CC cholesterol = an N-acylsphing-4-enine + cholesteryl 3-beta-D- CC galactoside; Xref=Rhea:RHEA:70235, ChEBI:CHEBI:16113, CC ChEBI:CHEBI:18390, ChEBI:CHEBI:52639, ChEBI:CHEBI:189066; CC Evidence={ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70236; CC Evidence={ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70237; CC Evidence={ECO:0000305|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-(beta-D-galactosyl)-N-dodecanoylsphing-4-enine + cholesterol CC = cholesteryl 3-beta-D-galactoside + N-dodecanoylsphing-4-enine; CC Xref=Rhea:RHEA:70255, ChEBI:CHEBI:16113, ChEBI:CHEBI:72956, CC ChEBI:CHEBI:73432, ChEBI:CHEBI:189066; CC Evidence={ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70256; CC Evidence={ECO:0000269|PubMed:32144204}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70257; CC Evidence={ECO:0000305|PubMed:32144204}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine + cholesterol = CC an N-acylsphing-4-enine + cholesteryl 3-beta-D-xyloside; CC Xref=Rhea:RHEA:70239, ChEBI:CHEBI:16113, ChEBI:CHEBI:52639, CC ChEBI:CHEBI:189067, ChEBI:CHEBI:189068; CC Evidence={ECO:0000269|PubMed:33361282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70240; CC Evidence={ECO:0000269|PubMed:33361282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-xylosyl-(1<->1')-N-(9Z-octadecenoyl)-sphing-4-enine + CC cholesterol = cholesteryl 3-beta-D-xyloside + N-(9Z-octadecenoyl)- CC sphing-4-enine; Xref=Rhea:RHEA:70251, ChEBI:CHEBI:16113, CC ChEBI:CHEBI:77996, ChEBI:CHEBI:189067, ChEBI:CHEBI:189081; CC Evidence={ECO:0000269|PubMed:33361282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70252; CC Evidence={ECO:0000269|PubMed:33361282}; CC -!- ACTIVITY REGULATION: Synergistically activated by saposin-A and CC saposin-C, two saposin peptides produced by proteolytic processing of CC prosaposin/PSAP (PubMed:9201993). Saposin-C activates GBA1 through its CC recruitment to membranes (PubMed:10781797, PubMed:9201993). The CC membrane structure and composition in anionic phospholipids are also CC important for the activation (PubMed:9201993, PubMed:10781797). CC Activated by PKC in the salvage pathway of ceramide formation CC (PubMed:19279011). Inhibited by conduritol B epoxide/CBE CC (PubMed:24211208, PubMed:26724485). {ECO:0000269|PubMed:10781797, CC ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208, CC ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:9201993}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 5.3. {ECO:0000269|PubMed:24211208}; CC Temperature dependence: CC Optimum temperature is 43 degrees Celsius. CC {ECO:0000269|PubMed:24211208}; CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism. CC {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485}. CC -!- PATHWAY: Sphingolipid metabolism. {ECO:0000269|PubMed:16293621, CC ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, CC ECO:0000269|PubMed:9201993}. CC -!- SUBUNIT: Interacts with saposin-C (PubMed:10781797). Interacts with CC SCARB2 (PubMed:18022370). Interacts with TCP1 (PubMed:21098288). May CC interacts with SNCA; this interaction may inhibit the CC glucosylceramidase activity (PubMed:23266198). Interacts with GRN; this CC interaction prevents aggregation of GBA1-SCARB2 complex via interaction CC with HSPA1A upon stress (PubMed:27789271). CC {ECO:0000269|PubMed:10781797, ECO:0000269|PubMed:18022370, CC ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:23266198, CC ECO:0000269|PubMed:27789271}. CC -!- INTERACTION: CC P04062; P17987: TCP1; NbExp=2; IntAct=EBI-1564609, EBI-356553; CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:17187079, CC ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:18022370}; Peripheral CC membrane protein {ECO:0000269|PubMed:10781797, CC ECO:0000269|PubMed:18022370, ECO:0000269|PubMed:1848227}; Lumenal side CC {ECO:0000269|PubMed:18022370}. Note=Interaction with saposin-C promotes CC membrane association (PubMed:10781797). Targeting to lysosomes occurs CC through an alternative MPR-independent mechanism via SCARB2 CC (PubMed:18022370). {ECO:0000269|PubMed:10781797, CC ECO:0000269|PubMed:18022370}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=5; CC Name=Long; CC IsoId=P04062-1; Sequence=Displayed; CC Name=Short; CC IsoId=P04062-2; Sequence=VSP_018800; CC Name=3; CC IsoId=P04062-3; Sequence=VSP_025216, VSP_025217, VSP_025218; CC Name=4; CC IsoId=P04062-4; Sequence=VSP_054655; CC Name=5; CC IsoId=P04062-5; Sequence=VSP_054656; CC -!- DISEASE: Gaucher disease (GD) [MIM:230800]: An autosomal recessive CC lysosomal storage disease due to deficient activity of lysosomal beta- CC glucocerebrosidase, and characterized by accumulation of CC glucosylceramide in the reticulo-endothelial system. GD is a CC multisystem disease historically divided into three main subtypes on CC the basis of the presence of neurologic involvement, age at onset and CC progression rate: type 1 is the non-neuropathic form, type 2 is the CC acute neuropathic form with early onset and rapid neurologic CC deterioration, type 3 is the chronic neuropathic form with slow CC progression of neurologic features. GD shows a marked phenotypic CC diversity ranging from adult asymptomatic forms, at the mild end, to CC perinatal lethal forms at the severe end of the disease spectrum. CC Formal diagnosis of Gaucher disease is based on the measurement of CC glucocerebrosidase levels in circulating leukocytes and molecular CC genetic analysis. {ECO:0000269|PubMed:10352942, CC ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10744424, CC ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:11992489, CC ECO:0000269|PubMed:15292921, ECO:0000269|PubMed:15826241, CC ECO:0000269|PubMed:15916907, ECO:0000269|PubMed:16293621, CC ECO:0000269|PubMed:17620502, ECO:0000269|PubMed:18332251, CC ECO:0000269|PubMed:1972019, ECO:0000269|PubMed:1974409, CC ECO:0000269|PubMed:19846850, ECO:0000269|PubMed:7475546, CC ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:7627192, CC ECO:0000269|PubMed:8076951, ECO:0000269|PubMed:8294033, CC ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8432537, CC ECO:0000269|PubMed:8829654, ECO:0000269|PubMed:8829663, CC ECO:0000269|PubMed:8937765, ECO:0000269|PubMed:9061570, CC ECO:0000269|PubMed:9182788, ECO:0000269|PubMed:9217217, CC ECO:0000269|PubMed:9516376, ECO:0000269|PubMed:9554454, CC ECO:0000269|PubMed:9650766}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Gaucher disease 1 (GD1) [MIM:230800]: A form of Gaucher CC disease, an autosomal recessive lysosomal storage disease due to CC deficient activity of lysosomal beta-glucocerebrosidase, and CC characterized by accumulation of glucosylceramide in the reticulo- CC endothelial system. GD1 is characterized by hepatosplenomegaly with CC consequent anemia and thrombopenia, and bone involvement. The central CC nervous system is not involved. {ECO:0000269|PubMed:10206680, CC ECO:0000269|PubMed:10340647, ECO:0000269|PubMed:10360404, CC ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, CC ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:1301953, CC ECO:0000269|PubMed:1487244, ECO:0000269|PubMed:15605411, CC ECO:0000269|PubMed:1864608, ECO:0000269|PubMed:1899336, CC ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:22658918, CC ECO:0000269|PubMed:2269438, ECO:0000269|PubMed:24022302, CC ECO:0000269|PubMed:24434810, ECO:0000269|PubMed:24577513, CC ECO:0000269|PubMed:2508065, ECO:0000269|PubMed:27825739, CC ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:36776904, CC ECO:0000269|PubMed:7655857, ECO:0000269|PubMed:7915932, CC ECO:0000269|PubMed:7916532, ECO:0000269|PubMed:8294487, CC ECO:0000269|PubMed:8432537, ECO:0000269|PubMed:8547070, CC ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8790604, CC ECO:0000269|PubMed:8829663, ECO:0000269|PubMed:8889591, CC ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9153297, CC ECO:0000269|PubMed:9240741, ECO:0000269|PubMed:9295080, CC ECO:0000269|PubMed:9554746, ECO:0000269|PubMed:9683600, CC ECO:0000269|PubMed:9856561, ECO:0000269|Ref.14}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Gaucher disease 2 (GD2) [MIM:230900]: The most severe form of CC Gaucher disease, an autosomal recessive lysosomal storage disease due CC to deficient activity of lysosomal beta-glucocerebrosidase, and CC characterized by accumulation of glucosylceramide in the reticulo- CC endothelial system. GD2 is an acute neuronopathic form that manifests CC soon after birth, with death generally occurring before patients reach CC two years of age. Clinical features include hepatosplenomegaly, CC developmental regression, growth arrest, and rapidly progressing CC neurologic deterioration. {ECO:0000269|PubMed:10360404, CC ECO:0000269|PubMed:10649495, ECO:0000269|PubMed:10679038, CC ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, CC ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:15690354, CC ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:21098288, CC ECO:0000269|PubMed:2269438, ECO:0000269|PubMed:24022302, CC ECO:0000269|PubMed:2464926, ECO:0000269|PubMed:27825739, CC ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:7627192, CC ECO:0000269|PubMed:7981693, ECO:0000269|PubMed:8112750, CC ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8598642, CC ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9240741, CC ECO:0000269|PubMed:9279145, ECO:0000269|PubMed:9554454, CC ECO:0000269|PubMed:9554746, ECO:0000269|PubMed:9637431, CC ECO:0000269|PubMed:9851895, ECO:0000269|PubMed:9856561}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Gaucher disease 3 (GD3) [MIM:231000]: A form of Gaucher CC disease, an autosomal recessive lysosomal storage disease due to CC deficient activity of lysosomal beta-glucocerebrosidase, and CC characterized by accumulation of glucosylceramide in the reticulo- CC endothelial system. GD3 is a subacute neuronopathic form characterized CC by later onset and slower progression compared to Gaucher disease 2. CC {ECO:0000269|PubMed:10360404, ECO:0000269|PubMed:10796875, CC ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:12204005, CC ECO:0000269|PubMed:1487244, ECO:0000269|PubMed:24022302, CC ECO:0000269|PubMed:2508065, ECO:0000269|PubMed:32547927, CC ECO:0000269|PubMed:34106956, ECO:0000269|PubMed:8294487, CC ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8780099, CC ECO:0000269|PubMed:9683600}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Gaucher disease 3C (GD3C) [MIM:231005]: A variant of subacute CC neuronopathic Gaucher disease 3 associated with cardiovascular CC calcifications. {ECO:0000269|PubMed:9040001}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Gaucher disease perinatal lethal (GDPL) [MIM:608013]: Distinct CC form of Gaucher disease type 2, characterized by fetal onset. Hydrops CC fetalis, in utero fetal death and neonatal distress are prominent CC features. When hydrops is absent, neurologic involvement begins in the CC first week and leads to death within 3 months. Hepatosplenomegaly is a CC major sign, and is associated with ichthyosis, arthrogryposis, and CC facial dysmorphism. {ECO:0000269|PubMed:10352942, CC ECO:0000269|PubMed:11933202}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Perinatal lethal Gaucher CC disease is associated with non-immune hydrops fetalis, a generalized CC edema of the fetus with fluid accumulation in the body cavities due to CC non-immune causes. Non-immune hydrops fetalis is not a diagnosis in CC itself but a symptom, a feature of many genetic disorders, and the end- CC stage of a wide variety of disorders. {ECO:0000269|PubMed:10352942}. CC -!- DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex CC neurodegenerative disorder characterized by bradykinesia, resting CC tremor, muscular rigidity and postural instability. Additional features CC are characteristic postural abnormalities, dysautonomia, dystonic CC cramps, and dementia. The pathology of Parkinson disease involves the CC loss of dopaminergic neurons in the substantia nigra and the presence CC of Lewy bodies (intraneuronal accumulations of aggregated proteins), in CC surviving neurons in various areas of the brain. The disease is CC progressive and usually manifests after the age of 50 years, although CC early-onset cases (before 50 years) are known. The majority of the CC cases are sporadic suggesting a multifactorial etiology based on CC environmental and genetic factors. However, some patients present with CC a positive family history for the disease. Familial forms of the CC disease usually begin at earlier ages and are associated with atypical CC clinical features. {ECO:0000269|PubMed:12847165, CC ECO:0000269|PubMed:16148263, ECO:0000269|PubMed:17620502, CC ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:19286695, CC ECO:0000269|PubMed:19846850}. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Available under the names Ceredase and Cerenzyme CC (Genzyme). Used to treat Gaucher disease. CC -!- MISCELLANEOUS: [Isoform Long]: Major isoform. CC {ECO:0000269|PubMed:3687939}. CC -!- MISCELLANEOUS: [Isoform Short]: Produced by alternative initiation from CC a downstream AUG. Two to three times less protein is produced from this CC downstream AUG. {ECO:0000269|PubMed:3687939}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 30 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Ceredase; Note=Clinical information on Ceredase; CC URL="https://www.rxlist.com/ceredase-drug.htm"; CC -!- WEB RESOURCE: Name=Cerenzyme; Note=Clinical information on Cerenzyme; CC URL="https://www.rxlist.com/cerenzyme-drug.htm"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M16328; AAA35873.1; -; mRNA. DR EMBL; K02920; AAA35877.1; -; mRNA. DR EMBL; J03059; AAC63056.1; -; Genomic_DNA. DR EMBL; D13286; BAA02545.1; -; mRNA. DR EMBL; D13287; BAA02546.1; -; mRNA. DR EMBL; AF023268; AAC51820.1; -; Genomic_DNA. DR EMBL; AK291911; BAF84600.1; -; mRNA. DR EMBL; AK298900; BAH12898.1; -; mRNA. DR EMBL; AK300829; BAH13357.1; -; mRNA. DR EMBL; AL713999; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003356; AAH03356.1; -; mRNA. DR EMBL; M19285; AAA35880.1; -; mRNA. DR EMBL; M18916; AAA35878.1; ALT_SEQ; Genomic_DNA. DR EMBL; M18917; AAA35879.1; ALT_SEQ; Genomic_DNA. DR EMBL; M20248; AAA35874.1; -; Genomic_DNA. DR EMBL; M20282; AAA35876.1; -; Genomic_DNA. DR CCDS; CCDS1102.1; -. [P04062-1] DR CCDS; CCDS53373.1; -. [P04062-4] DR CCDS; CCDS53374.1; -. [P04062-5] DR PIR; A94068; EUHUGC. DR PIR; I52980; I52980. DR PIR; I67792; I67792. DR RefSeq; NP_000148.2; NM_000157.3. [P04062-1] DR RefSeq; NP_001005741.1; NM_001005741.2. [P04062-1] DR RefSeq; NP_001005742.1; NM_001005742.2. [P04062-1] DR RefSeq; NP_001165282.1; NM_001171811.1. [P04062-4] DR RefSeq; NP_001165283.1; NM_001171812.1. [P04062-5] DR PDB; 1OGS; X-ray; 2.00 A; A/B=40-536. DR PDB; 1Y7V; X-ray; 2.40 A; A/B=40-536. DR PDB; 2F61; X-ray; 2.50 A; A/B=40-536. DR PDB; 2J25; X-ray; 2.90 A; A/B=40-536. DR PDB; 2NSX; X-ray; 2.11 A; A/B/C/D=40-536. DR PDB; 2NT0; X-ray; 1.79 A; A/B/C/D=40-536. DR PDB; 2NT1; X-ray; 2.30 A; A/B/C/D=40-536. DR PDB; 2V3D; X-ray; 1.96 A; A/B=40-536. DR PDB; 2V3E; X-ray; 2.00 A; A/B=40-536. DR PDB; 2V3F; X-ray; 1.95 A; A/B=40-536. DR PDB; 2VT0; X-ray; 2.15 A; A/B=40-536. DR PDB; 2WCG; X-ray; 2.30 A; A/B=40-536. DR PDB; 2WKL; X-ray; 2.70 A; A/B=40-536. DR PDB; 2XWD; X-ray; 2.66 A; A/B=40-536. DR PDB; 2XWE; X-ray; 2.31 A; A/B=40-536. DR PDB; 3GXD; X-ray; 2.50 A; A/B/C/D=40-536. DR PDB; 3GXF; X-ray; 2.40 A; A/B/C/D=40-536. DR PDB; 3GXI; X-ray; 1.84 A; A/B/C/D=40-536. DR PDB; 3GXM; X-ray; 2.20 A; A/B/C/D=40-536. DR PDB; 3KE0; X-ray; 2.70 A; A/B=40-536. DR PDB; 3KEH; X-ray; 2.80 A; A/B=40-536. DR PDB; 3RIK; X-ray; 2.48 A; A/B/C/D=40-536. DR PDB; 3RIL; X-ray; 2.40 A; A/B/C/D=40-536. DR PDB; 5LVX; X-ray; 2.20 A; A/B/C/D=40-536. DR PDB; 6MOZ; X-ray; 2.10 A; A/B=40-536. DR PDB; 6Q1N; X-ray; 2.53 A; A/B=40-536. DR PDB; 6Q1P; X-ray; 2.80 A; A/B=40-536. DR PDB; 6Q6K; X-ray; 1.92 A; A/B=40-536. DR PDB; 6Q6L; X-ray; 1.81 A; A/B=40-536. DR PDB; 6Q6N; X-ray; 1.63 A; A/B=40-536. DR PDB; 6T13; X-ray; 1.85 A; A/B/C/D=1-536. DR PDB; 6TJJ; X-ray; 1.59 A; AAA/BBB=40-536. DR PDB; 6TJK; X-ray; 1.56 A; AAA/BBB=40-536. DR PDB; 6TJQ; X-ray; 1.41 A; BBB=40-536. DR PDB; 6TN1; X-ray; 0.98 A; AAA=40-536. DR PDB; 6YTP; X-ray; 1.70 A; AAA/BBB=40-536. DR PDB; 6YTR; X-ray; 1.70 A; AAA/BBB=40-536. DR PDB; 6YUT; X-ray; 1.76 A; AAA/BBB=40-536. DR PDB; 6YV3; X-ray; 1.80 A; AAA/BBB=40-536. DR PDB; 6Z39; X-ray; 1.70 A; AAA/BBB=40-536. DR PDB; 6Z3I; X-ray; 1.80 A; BBB=40-536. DR PDB; 7NWV; X-ray; 1.86 A; AAA/BBB=40-536. DR PDBsum; 1OGS; -. DR PDBsum; 1Y7V; -. DR PDBsum; 2F61; -. DR PDBsum; 2J25; -. DR PDBsum; 2NSX; -. DR PDBsum; 2NT0; -. DR PDBsum; 2NT1; -. DR PDBsum; 2V3D; -. DR PDBsum; 2V3E; -. DR PDBsum; 2V3F; -. DR PDBsum; 2VT0; -. DR PDBsum; 2WCG; -. DR PDBsum; 2WKL; -. DR PDBsum; 2XWD; -. DR PDBsum; 2XWE; -. DR PDBsum; 3GXD; -. DR PDBsum; 3GXF; -. DR PDBsum; 3GXI; -. DR PDBsum; 3GXM; -. DR PDBsum; 3KE0; -. DR PDBsum; 3KEH; -. DR PDBsum; 3RIK; -. DR PDBsum; 3RIL; -. DR PDBsum; 5LVX; -. DR PDBsum; 6MOZ; -. DR PDBsum; 6Q1N; -. DR PDBsum; 6Q1P; -. DR PDBsum; 6Q6K; -. DR PDBsum; 6Q6L; -. DR PDBsum; 6Q6N; -. DR PDBsum; 6T13; -. DR PDBsum; 6TJJ; -. DR PDBsum; 6TJK; -. DR PDBsum; 6TJQ; -. DR PDBsum; 6TN1; -. DR PDBsum; 6YTP; -. DR PDBsum; 6YTR; -. DR PDBsum; 6YUT; -. DR PDBsum; 6YV3; -. DR PDBsum; 6Z39; -. DR PDBsum; 6Z3I; -. DR PDBsum; 7NWV; -. DR AlphaFoldDB; P04062; -. DR SMR; P04062; -. DR BioGRID; 108899; 130. DR DIP; DIP-38645N; -. DR IntAct; P04062; 38. DR MINT; P04062; -. DR STRING; 9606.ENSP00000314508; -. DR BindingDB; P04062; -. DR ChEMBL; CHEMBL2179; -. DR DrugBank; DB08283; (2R,3R,4R,5S)-2-(HYDROXYMETHYL)-1-NONYLPIPERIDINE-3,4,5-TRIOL. DR DrugBank; DB03740; N-acetyl-alpha-D-glucosamine. DR DrugBank; DB03106; scyllo-inositol. DR DrugBank; DB06720; Velaglucerase alfa. DR DrugCentral; P04062; -. DR SwissLipids; SLP:000001387; -. DR Allergome; 8244; Hom s Glucocerebrosidase. DR CAZy; GH30; Glycoside Hydrolase Family 30. DR GlyConnect; 1271; 26 N-Linked glycans (4 sites). DR GlyCosmos; P04062; 6 sites, 29 glycans. DR GlyGen; P04062; 8 sites, 28 N-linked glycans (4 sites), 1 O-linked glycan (2 sites). DR iPTMnet; P04062; -. DR MetOSite; P04062; -. DR PhosphoSitePlus; P04062; -. DR SwissPalm; P04062; -. DR BioMuta; GBA; -. DR DMDM; 55584151; -. DR EPD; P04062; -. DR jPOST; P04062; -. DR MassIVE; P04062; -. DR MaxQB; P04062; -. DR PaxDb; 9606-ENSP00000314508; -. DR PeptideAtlas; P04062; -. DR ProteomicsDB; 51642; -. [P04062-1] DR ProteomicsDB; 51643; -. [P04062-2] DR ProteomicsDB; 51644; -. [P04062-3] DR Pumba; P04062; -. DR ABCD; P04062; 7 sequenced antibodies. DR Antibodypedia; 1678; 565 antibodies from 34 providers. DR DNASU; 2629; -. DR Ensembl; ENST00000327247.9; ENSP00000314508.5; ENSG00000177628.16. [P04062-1] DR Ensembl; ENST00000368373.8; ENSP00000357357.3; ENSG00000177628.16. [P04062-1] DR Ensembl; ENST00000427500.7; ENSP00000402577.2; ENSG00000177628.16. [P04062-5] DR Ensembl; ENST00000428024.3; ENSP00000397986.2; ENSG00000177628.16. [P04062-4] DR GeneID; 2629; -. DR KEGG; hsa:2629; -. DR MANE-Select; ENST00000368373.8; ENSP00000357357.3; NM_000157.4; NP_000148.2. DR UCSC; uc001fjh.4; human. [P04062-1] DR AGR; HGNC:4177; -. DR CTD; 2629; -. DR DisGeNET; 2629; -. DR GeneCards; GBA1; -. DR GeneReviews; GBA1; -. DR HGNC; HGNC:4177; GBA1. DR HPA; ENSG00000177628; Low tissue specificity. DR MalaCards; GBA1; -. DR MIM; 168600; phenotype. DR MIM; 230800; phenotype. DR MIM; 230900; phenotype. DR MIM; 231000; phenotype. DR MIM; 231005; phenotype. DR MIM; 606463; gene. DR MIM; 608013; phenotype. DR neXtProt; NX_P04062; -. DR OpenTargets; ENSG00000177628; -. DR Orphanet; 85212; Fetal Gaucher disease. DR Orphanet; 77259; Gaucher disease type 1. DR Orphanet; 77260; Gaucher disease type 2. DR Orphanet; 77261; Gaucher disease type 3. DR Orphanet; 2072; Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome. DR Orphanet; 411602; Hereditary late-onset Parkinson disease. DR Orphanet; 1648; NON RARE IN EUROPE: Dementia with Lewy body. DR Orphanet; 319705; NON RARE IN EUROPE: Parkinson disease. DR PharmGKB; PA28591; -. DR VEuPathDB; HostDB:ENSG00000177628; -. DR eggNOG; KOG2566; Eukaryota. DR GeneTree; ENSGT00390000009464; -. DR HOGENOM; CLU_014379_1_2_1; -. DR InParanoid; P04062; -. DR OMA; FGGIAWH; -. DR OrthoDB; 3473901at2759; -. DR PhylomeDB; P04062; -. DR TreeFam; TF314254; -. DR BRENDA; 3.2.1.45; 2681. DR PathwayCommons; P04062; -. DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis. DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism. DR SignaLink; P04062; -. DR UniPathway; UPA00296; -. DR BioGRID-ORCS; 2629; 10 hits in 1162 CRISPR screens. DR ChiTaRS; GBA; human. DR EvolutionaryTrace; P04062; -. DR GeneWiki; Glucocerebrosidase; -. DR GenomeRNAi; 2629; -. DR Pharos; P04062; Tclin. DR PRO; PR:P04062; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P04062; Protein. DR Bgee; ENSG00000177628; Expressed in stromal cell of endometrium and 101 other cell types or tissues. DR ExpressionAtlas; P04062; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0043202; C:lysosomal lumen; ISS:BHF-UCL. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IMP:ARUK-UCL. DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB. DR GO; GO:0004336; F:galactosylceramidase activity; IEA:RHEA. DR GO; GO:0004348; F:glucosylceramidase activity; IDA:UniProtKB. DR GO; GO:0046527; F:glucosyltransferase activity; IDA:UniProtKB. DR GO; GO:0005124; F:scavenger receptor binding; IPI:ARUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; ISS:BHF-UCL. DR GO; GO:0050295; F:steryl-beta-glucosidase activity; IDA:UniProtKB. DR GO; GO:0019882; P:antigen processing and presentation; IEA:Ensembl. DR GO; GO:1905037; P:autophagosome organization; IEA:Ensembl. DR GO; GO:0006914; P:autophagy; IMP:UniProtKB. DR GO; GO:1901805; P:beta-glucoside catabolic process; IEA:Ensembl. DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl. DR GO; GO:0048469; P:cell maturation; IEA:Ensembl. DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL. DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:BHF-UCL. DR GO; GO:0021694; P:cerebellar Purkinje cell layer formation; IEA:Ensembl. DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB. DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl. DR GO; GO:0061436; P:establishment of skin barrier; IEA:Ensembl. DR GO; GO:0006680; P:glucosylceramide catabolic process; IDA:UniProtKB. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0030259; P:lipid glycosylation; IDA:UniProtKB. DR GO; GO:0019915; P:lipid storage; IEA:Ensembl. DR GO; GO:0072676; P:lymphocyte migration; IEA:Ensembl. DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB. DR GO; GO:0014004; P:microglia differentiation; IEA:Ensembl. DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl. DR GO; GO:0061744; P:motor behavior; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:BHF-UCL. DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:BHF-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IEA:Ensembl. DR GO; GO:1904457; P:positive regulation of neuronal action potential; IMP:ParkinsonsUK-UCL. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:BHF-UCL. DR GO; GO:1903061; P:positive regulation of protein lipidation; IGI:ParkinsonsUK-UCL. DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IDA:ParkinsonsUK-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0021859; P:pyramidal neuron differentiation; IEA:Ensembl. DR GO; GO:1905165; P:regulation of lysosomal protein catabolic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB. DR GO; GO:0022904; P:respiratory electron transport chain; IEA:Ensembl. DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0009268; P:response to pH; IEA:Ensembl. DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl. DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl. DR GO; GO:0046512; P:sphingosine biosynthetic process; IMP:BHF-UCL. DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0023021; P:termination of signal transduction; IMP:BHF-UCL. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR InterPro; IPR033452; GH30_C. DR InterPro; IPR001139; Glyco_hydro_30. DR InterPro; IPR033453; Glyco_hydro_30_TIM-barrel. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR PANTHER; PTHR11069; GLUCOSYLCERAMIDASE; 1. DR PANTHER; PTHR11069:SF33; LYSOSOMAL ACID GLUCOSYLCERAMIDASE; 1. DR Pfam; PF02055; Glyco_hydro_30; 1. DR Pfam; PF17189; Glyco_hydro_30C; 1. DR PRINTS; PR00843; GLHYDRLASE30. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 2. DR Genevisible; P04062; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Alternative splicing; KW Cholesterol metabolism; Direct protein sequencing; Disease variant; KW Disulfide bond; Gaucher disease; Glycoprotein; Glycosidase; KW Glycosyltransferase; Hydrolase; Ichthyosis; Lipid metabolism; Lysosome; KW Membrane; Neurodegeneration; Parkinson disease; Parkinsonism; KW Pharmaceutical; Reference proteome; Signal; Sphingolipid metabolism; KW Steroid metabolism; Sterol metabolism; Transferase. FT SIGNAL 1..39 FT /evidence="ECO:0000269|Ref.12" FT CHAIN 40..536 FT /note="Lysosomal acid glucosylceramidase" FT /id="PRO_0000012177" FT ACT_SITE 274 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:15817452" FT ACT_SITE 379 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:15817452" FT CARBOHYD 58 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12792654, FT ECO:0000269|PubMed:17139081" FT CARBOHYD 98 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:17139081, ECO:0000269|PubMed:19159218" FT CARBOHYD 185 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:17139081" FT CARBOHYD 309 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19159218" FT CARBOHYD 501 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 43..55 FT /evidence="ECO:0000269|PubMed:12792654, FT ECO:0007744|PDB:1OGS" FT DISULFID 57..62 FT /evidence="ECO:0000269|PubMed:12792654, FT ECO:0007744|PDB:1OGS" FT VAR_SEQ 1..161 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8294033" FT /id="VSP_025216" FT VAR_SEQ 1..87 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054655" FT VAR_SEQ 1..20 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:3001061, FT ECO:0000303|PubMed:3864160" FT /id="VSP_018800" FT VAR_SEQ 103..151 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054656" FT VAR_SEQ 422..423 FT /note="LA -> PS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8294033" FT /id="VSP_025217" FT VAR_SEQ 425..536 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8294033" FT /id="VSP_025218" FT VARIANT 46 FT /note="K -> E (found in a patient with Parkinson disease; FT uncertain significance; dbSNP:rs142761046)" FT /evidence="ECO:0000269|PubMed:19286695" FT /id="VAR_063066" FT VARIANT 54 FT /note="V -> L (in GD; dbSNP:rs121908302)" FT /evidence="ECO:0000269|PubMed:8829654" FT /id="VAR_003255" FT VARIANT 55 FT /note="C -> S (in GD; neuronopathic and perinatal lethal FT forms; loss of glucosylceramidase activity; FT dbSNP:rs773007510)" FT /evidence="ECO:0000269|PubMed:11992489, FT ECO:0000269|PubMed:15292921, ECO:0000269|PubMed:16293621" FT /id="VAR_032394" FT VARIANT 62 FT /note="C -> W (in GD1)" FT /evidence="ECO:0000269|PubMed:24434810" FT /id="VAR_081188" FT VARIANT 63 FT /note="D -> N (in GD1; very low glucosylceramidase FT activity)" FT /evidence="ECO:0000269|PubMed:15605411" FT /id="VAR_032395" FT VARIANT 76 FT /note="F -> V (in GD)" FT /evidence="ECO:0000269|PubMed:9217217" FT /id="VAR_003256" FT VARIANT 80 FT /note="E -> K (in GD2)" FT /evidence="ECO:0000269|PubMed:9851895" FT /id="VAR_009033" FT VARIANT 82 FT /note="T -> I (in GD1; dbSNP:rs1141811)" FT /evidence="ECO:0000269|PubMed:7655857" FT /id="VAR_003257" FT VARIANT 85 FT /note="G -> E (in GD; dbSNP:rs77829017)" FT /evidence="ECO:0000269|PubMed:8829654, FT ECO:0000269|PubMed:9217217" FT /id="VAR_003258" FT VARIANT 87 FT /note="R -> Q (in GD1; decreased glucosylceramidase FT activity; 20% of normal activity; dbSNP:rs78769774)" FT /evidence="ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:32547927" FT /id="VAR_032197" FT VARIANT 87 FT /note="R -> W (in GD1; decreased glucosylceramidase FT activity; dbSNP:rs1141814)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:7655857, ECO:0000269|PubMed:9153297, FT ECO:0000269|PubMed:9217217, ECO:0000269|PubMed:9295080, FT ECO:0000269|PubMed:9683600, ECO:0000269|PubMed:9856561" FT /id="VAR_003259" FT VARIANT 92 FT /note="M -> T (in dbSNP:rs1141815)" FT /id="VAR_032396" FT VARIANT 118 FT /note="K -> N (in GD1; mild; decreased glucosylceramidase FT activity; 8% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs121908312)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:16293621" FT /id="VAR_003260" FT VARIANT 120 FT /note="F -> L (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088437" FT VARIANT 129 FT /note="A -> T (in GD1)" FT /evidence="ECO:0000269|PubMed:10796875" FT /id="VAR_032397" FT VARIANT 146 FT /note="S -> L (in GD2 and GD3; dbSNP:rs758447515)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:9554454" FT /id="VAR_009034" FT VARIANT 147 FT /note="Y -> C (in GD3)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088438" FT VARIANT 152 FT /note="G -> E (in GD1)" FT /evidence="ECO:0000269|PubMed:9554746" FT /id="VAR_003261" FT VARIANT 155 FT /note="Y -> H (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088439" FT VARIANT 156 FT /note="N -> D (in GD1)" FT /evidence="ECO:0000269|PubMed:10796875" FT /id="VAR_032398" FT VARIANT 158 FT /note="I -> S (in GD1; very low glucosylceramidase FT activity; dbSNP:rs77834747)" FT /evidence="ECO:0000269|PubMed:15605411" FT /id="VAR_032399" FT VARIANT 158 FT /note="I -> T (in GD1; dbSNP:rs77834747)" FT /evidence="ECO:0000269|PubMed:9683600" FT /id="VAR_003262" FT VARIANT 159 FT /note="R -> Q (in GD1 and GD2; decreased glucosylceramidase FT activity; 13% of normal activity; dbSNP:rs79653797)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:16293621" FT /id="VAR_003263" FT VARIANT 159 FT /note="R -> W (in GD1 and GD2; dbSNP:rs439898)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:9217217, ECO:0000269|PubMed:9683600, FT ECO:0000269|PubMed:9856561" FT /id="VAR_003264" FT VARIANT 161 FT /note="P -> L (in GD; decreased glucosylceramidase FT activity; 16% of normal activity; dbSNP:rs79637617)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032198" FT VARIANT 161 FT /note="P -> S (in GD1; dbSNP:rs121908299)" FT /evidence="ECO:0000269|PubMed:8432537" FT /id="VAR_003265" FT VARIANT 162 FT /note="M -> V (in GD; loss of glucosylceramidase activity; FT increases susceptibility to proteolytic degradation; FT dbSNP:rs377325220)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032199" FT VARIANT 166 FT /note="D -> V (in GD; decreased glucosylceramidase FT activity; 9% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs79796061)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032200" FT VARIANT 170 FT /note="R -> C (in GD1 and GD2; also found in a patient with FT Parkinson disease; dbSNP:rs398123530)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:19286695, FT ECO:0000269|PubMed:9851895" FT /id="VAR_009035" FT VARIANT 170 FT /note="R -> L (in GD1 and GD2; dbSNP:rs80356763)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:10796875" FT /id="VAR_009036" FT VARIANT 173 FT /note="T -> I (in GD1; dbSNP:rs78657146)" FT /evidence="ECO:0000269|PubMed:10796875" FT /id="VAR_032400" FT VARIANT 173 FT /note="T -> P (in GD1; dbSNP:rs1441909908)" FT /evidence="ECO:0000269|PubMed:10447266, FT ECO:0000269|PubMed:9554746" FT /id="VAR_003266" FT VARIANT 174 FT /note="Y -> S (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088440" FT VARIANT 175 FT /note="A -> E (in GD; dbSNP:rs79660787)" FT /evidence="ECO:0000269|PubMed:11933202" FT /id="VAR_032401" FT VARIANT 179 FT /note="D -> H (in GD1; decreased glucosylceramide catabolic FT process; dbSNP:rs147138516)" FT /evidence="ECO:0000269|PubMed:15916907, FT ECO:0000269|PubMed:1864608" FT /id="VAR_003267" FT VARIANT 196 FT /note="K -> Q (in GD1; decreased protein abundance; FT decreased glucosylceramide catabolic process; FT dbSNP:rs121908297)" FT /evidence="ECO:0000269|PubMed:15916907, FT ECO:0000269|PubMed:1864608, ECO:0000269|PubMed:1899336" FT /id="VAR_003268" FT VARIANT 198 FT /note="P -> L (in GD; dbSNP:rs80222298)" FT /evidence="ECO:0000269|PubMed:9554454" FT /id="VAR_009037" FT VARIANT 198 FT /note="P -> S (in GD1; decreased glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081189" FT VARIANT 198 FT /note="P -> T (in GD1)" FT /evidence="ECO:0000269|PubMed:12204005" FT /id="VAR_032402" FT VARIANT 200 FT /note="I -> N (in GD; decreased glucosylceramidase FT activity; 5% of normal activity; dbSNP:rs77933015)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032201" FT VARIANT 200 FT /note="I -> S (in GD1; dbSNP:rs77933015)" FT /evidence="ECO:0000269|PubMed:9856561" FT /id="VAR_010059" FT VARIANT 201 FT /note="H -> P (in GD1; dbSNP:rs76500263)" FT /evidence="ECO:0000269|PubMed:11933202" FT /id="VAR_032403" FT VARIANT 209 FT /note="R -> C (in GD1; dbSNP:rs398123532)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:12204005" FT /id="VAR_032404" FT VARIANT 209 FT /note="R -> P (in GD1; dbSNP:rs749416070)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:9683600" FT /id="VAR_003269" FT VARIANT 213 FT /note="L -> F (in GD; decreased glucosylceramidase FT activity; 12% of normal activity; dbSNP:rs374591570)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032202" FT VARIANT 214 FT /note="L -> P (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088441" FT VARIANT 215 FT /note="A -> D (in GD1)" FT /evidence="ECO:0000269|PubMed:8790604" FT /id="VAR_003270" FT VARIANT 217 FT /note="P -> S (in GD2)" FT /evidence="ECO:0000269|PubMed:7627192" FT /id="VAR_003271" FT VARIANT 221 FT /note="P -> L (in GD1; very low glucosylceramidase FT activity; dbSNP:rs80205046)" FT /evidence="ECO:0000269|PubMed:15605411" FT /id="VAR_032405" FT VARIANT 221 FT /note="P -> T (in GD1; dbSNP:rs866075757)" FT /evidence="ECO:0000269|PubMed:8790604" FT /id="VAR_003272" FT VARIANT 223 FT /note="W -> R (in GD1 and GD2; dbSNP:rs61748906)" FT /evidence="ECO:0000269|PubMed:10679038, FT ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:8294033" FT /id="VAR_003273" FT VARIANT 224 FT /note="L -> F (in GD; decreased glucosylceramidase FT activity; 4% of normal activity; increases susceptibility FT to proteolytic degradation)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032203" FT VARIANT 227 FT /note="N -> I (in GD2; decreased glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081190" FT VARIANT 227 FT /note="N -> K (in GD1 and GD2; dbSNP:rs381418)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:9683600" FT /id="VAR_003275" FT VARIANT 227 FT /note="N -> S (in GD1 and GD3; decreased glucosylceramide FT catabolic process; dbSNP:rs364897)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:24022302, FT ECO:0000269|PubMed:8829654, ECO:0000269|PubMed:9217217" FT /id="VAR_003274" FT VARIANT 228 FT /note="G -> V (in GD; dbSNP:rs78911246)" FT /evidence="ECO:0000269|PubMed:9061570" FT /id="VAR_010060" FT VARIANT 229 FT /note="A -> E (in GD2; dbSNP:rs75636769)" FT /evidence="ECO:0000269|PubMed:10649495" FT /id="VAR_009038" FT VARIANT 229 FT /note="A -> T (in GD3)" FT /evidence="ECO:0000269|PubMed:10796875" FT /id="VAR_032406" FT VARIANT 230 FT /note="V -> E (in GD1; very low glucosylceramidase FT activity; dbSNP:rs381427)" FT /evidence="ECO:0000269|PubMed:15605411" FT /id="VAR_032407" FT VARIANT 230 FT /note="V -> G (in GD1; dbSNP:rs381427)" FT /evidence="ECO:0000269|PubMed:10206680, FT ECO:0000269|PubMed:8294033" FT /id="VAR_003276" FT VARIANT 232 FT /note="G -> E (in GD; also found in a patient with FT Parkinson disease; decreased glucosylceramidase activity; FT 7% of normal activity; dbSNP:rs1376479747)" FT /evidence="ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:19286695" FT /id="VAR_032204" FT VARIANT 234 FT /note="G -> E (in GD1; severely decreased FT glucosylceramidase activity; dbSNP:rs74462743)" FT /evidence="ECO:0000269|PubMed:9153297" FT /id="VAR_003277" FT VARIANT 234 FT /note="G -> W (in GD)" FT /evidence="ECO:0000269|PubMed:10447266" FT /id="VAR_009039" FT VARIANT 235 FT /note="S -> P (in GD1 and GD2; dbSNP:rs1064644)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:8294033" FT /id="VAR_003278" FT VARIANT 237 FT /note="K -> E (in GD2; severe; loss of glucosylceramidase FT activity; increases susceptibility to proteolytic FT degradation; dbSNP:rs773409311)" FT /evidence="ECO:0000269|PubMed:11933202, FT ECO:0000269|PubMed:16293621" FT /id="VAR_032205" FT VARIANT 241 FT /note="G -> R (in GD1, GD2 and GD3; severely decreased FT glucosylceramidase activity; dbSNP:rs409652)" FT /evidence="ECO:0000269|PubMed:10360404, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:8294033, ECO:0000269|PubMed:8790604, FT ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9856561" FT /id="VAR_003279" FT VARIANT 244 FT /note="Y -> C (in GD1 and GD3; dbSNP:rs76026102)" FT /evidence="ECO:0000269|PubMed:10360404, FT ECO:0000269|PubMed:11933202" FT /id="VAR_010062" FT VARIANT 251 FT /note="Y -> H (in GD; uncertain significance; FT dbSNP:rs121908300)" FT /evidence="ECO:0000269|PubMed:8432537" FT /id="VAR_003280" FT VARIANT 252 FT /note="F -> I (in GD1, GD2 and GD3; dbSNP:rs381737)" FT /evidence="ECO:0000269|PubMed:10360404, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:1301953, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:8294033, ECO:0000269|PubMed:9061570, FT ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9217217" FT /id="VAR_003281" FT VARIANT 255 FT /note="F -> Y (in GD; loss of glucosylceramidase activity;; FT dbSNP:rs74500255)" FT /evidence="ECO:0000269|PubMed:1974409, FT ECO:0000269|PubMed:8294487" FT /id="VAR_003282" FT VARIANT 266 FT /note="F -> L (in GD1)" FT /evidence="ECO:0000269|PubMed:24577513" FT /id="VAR_081191" FT VARIANT 270 FT /note="T -> I (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088442" FT VARIANT 270 FT /note="T -> R (in GD2; dbSNP:rs76725886)" FT /evidence="ECO:0000269|PubMed:12204005" FT /id="VAR_032408" FT VARIANT 274 FT /note="E -> K (in GD2; loss of glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081192" FT VARIANT 276 FT /note="S -> P (in GD1)" FT /evidence="ECO:0000269|PubMed:9683600" FT /id="VAR_003283" FT VARIANT 284 FT /note="P -> T (in GD1; loss of glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081193" FT VARIANT 289 FT /note="G -> V (in GD1; dbSNP:rs878853321)" FT /evidence="ECO:0000269|PubMed:22658918" FT /id="VAR_081194" FT VARIANT 290 FT /note="F -> L (in GDPL; dbSNP:rs121908313)" FT /evidence="ECO:0000269|PubMed:11933202" FT /id="VAR_032409" FT VARIANT 294 FT /note="H -> Q (in GD1, GD2 and GD3; associated in cis with FT H-448 in all patients analyzed; uncertain significance; FT dbSNP:rs367968666)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:15690354, ECO:0000269|PubMed:32547927" FT /id="VAR_009040" FT VARIANT 296 FT /note="R -> Q (in GD1 and GD2; also found in a patient with FT Parkinson disease; dbSNP:rs78973108)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:19286695, FT ECO:0000269|PubMed:8790604" FT /id="VAR_003284" FT VARIANT 298 FT /note="F -> L (in GD and GD2; decreased glucosylceramidase FT activity; 4% of normal activity)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:3001061" FT /id="VAR_009041" FT VARIANT 301 FT /note="R -> G (in GD1)" FT /evidence="ECO:0000269|PubMed:22658918" FT /id="VAR_081195" FT VARIANT 303 FT /note="L -> I (in GD; decreased glucosylceramidase FT activity; 5% of normal activity; dbSNP:rs1296507371)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032206" FT VARIANT 304 FT /note="G -> D (in GD1; dbSNP:rs80116658)" FT /evidence="ECO:0000269|PubMed:9856561" FT /id="VAR_010063" FT VARIANT 304 FT /note="G -> R (in GD3; loss of glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081196" FT VARIANT 305 FT /note="P -> R (in GD1; dbSNP:rs79215220)" FT /evidence="ECO:0000269|PubMed:8547070" FT /id="VAR_003285" FT VARIANT 310 FT /note="S -> G (in dbSNP:rs1057942)" FT /evidence="ECO:0000269|PubMed:8294033" FT /id="VAR_032410" FT VARIANT 310 FT /note="S -> N (in GD1; severely decreased FT glucosylceramidase activity; less than 5% of normal FT activity; dbSNP:rs74731340)" FT /evidence="ECO:0000269|PubMed:9153297" FT /id="VAR_010064" FT VARIANT 322 FT /note="D -> N (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088443" FT VARIANT 324 FT /note="R -> C (in GD1 and GD3; dbSNP:rs765633380)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:15605411, FT ECO:0000269|PubMed:8790604, ECO:0000269|PubMed:9856561" FT /id="VAR_003286" FT VARIANT 324 FT /note="R -> H (in GD1 and GD2; dbSNP:rs79696831)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:12204005" FT /id="VAR_009042" FT VARIANT 328 FT /note="P -> L (in GD1; loss of glucosylceramidase activity; FT dbSNP:rs121908298)" FT /evidence="ECO:0000269|PubMed:1301953, FT ECO:0000269|PubMed:8294487" FT /id="VAR_003287" FT VARIANT 342 FT /note="K -> I (in GD1; dbSNP:rs77714449)" FT /evidence="ECO:0000269|PubMed:9683600" FT /id="VAR_003288" FT VARIANT 343 FT /note="Y -> C (in GD2; decreased glucosylceramidase FT activity; 16% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs77321207)" FT /evidence="ECO:0000269|PubMed:10649495, FT ECO:0000269|PubMed:16293621" FT /id="VAR_009043" FT VARIANT 347 FT /note="I -> S (in GD1)" FT /evidence="ECO:0000269|PubMed:24577513" FT /id="VAR_081197" FT VARIANT 348 FT /note="A -> V (in GD1; dbSNP:rs78396650)" FT /evidence="ECO:0000269|PubMed:1899336, FT ECO:0000269|PubMed:32547927" FT /id="VAR_003289" FT VARIANT 350 FT /note="H -> R (in GDPL, GD1 and GD2; dbSNP:rs78198234)" FT /evidence="ECO:0000269|PubMed:10352942, FT ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:32547927" FT /id="VAR_009044" FT VARIANT 351 FT /note="W -> C (in GD1; dbSNP:rs121908304)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:1899336" FT /id="VAR_003290" FT VARIANT 351 FT /note="W -> S (in GD1; loss of glucosylceramide catabolic FT process; dbSNP:rs1553217294)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081198" FT VARIANT 352 FT /note="Y -> H (in GD)" FT /evidence="ECO:0000269|PubMed:8829663" FT /id="VAR_003291" FT VARIANT 354 FT /note="D -> H (in GD1; uncertain significance; FT dbSNP:rs398123526)" FT /evidence="ECO:0000269|PubMed:8547070" FT /id="VAR_003292" FT VARIANT 357 FT /note="A -> D (in GD1; uncertain significance; FT dbSNP:rs78188205)" FT /evidence="ECO:0000269|PubMed:8547070" FT /id="VAR_003293" FT VARIANT 362 FT /note="T -> I (in GD1; decreased glucosylceramidase FT activity; 4-6% of normal activity; dbSNP:rs76539814)" FT /evidence="ECO:0000269|PubMed:1301953, FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:8294487" FT /id="VAR_003294" FT VARIANT 363 FT /note="L -> P (in GD1; uncertain significance; also found FT in a patient with Parkinson disease; uncertain FT significance; dbSNP:rs1178732315)" FT /evidence="ECO:0000269|PubMed:26528954, FT ECO:0000269|PubMed:9683600" FT /id="VAR_003295" FT VARIANT 364 FT /note="G -> R (in GD2; dbSNP:rs121908305)" FT /evidence="ECO:0000269|PubMed:2269438, FT ECO:0000269|PubMed:8294033" FT /id="VAR_003296" FT VARIANT 365 FT /note="E -> K (in GD1; benign; decreased glucosylceramidase FT activity; 42% of normal activity; dbSNP:rs2230288)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:11903352, ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:1864608, ECO:0000269|PubMed:24022302" FT /id="VAR_003297" FT VARIANT 368 FT /note="R -> H (in dbSNP:rs1064648)" FT /evidence="ECO:0000269|PubMed:8294033" FT /id="VAR_032411" FT VARIANT 380 FT /note="A -> T (in GD1; dbSNP:rs781306264)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:9554454" FT /id="VAR_009045" FT VARIANT 381 FT /note="C -> G (in GD2; loss of glucosylceramidase activity; FT dbSNP:rs121908306)" FT /evidence="ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:2269438" FT /id="VAR_003298" FT VARIANT 388 FT /note="E -> K (in GD; decreased glucosylceramidase FT activity; 12% of normal activity; dbSNP:rs1161552095)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032207" FT VARIANT 391 FT /note="V -> L (in GD1; decreased glucosylceramidase FT activity; dbSNP:rs398123527)" FT /evidence="ECO:0000269|PubMed:9153297" FT /id="VAR_010065" FT VARIANT 392 FT /note="R -> G (in GD and GD3; dbSNP:rs121908308)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:9650766" FT /id="VAR_010066" FT VARIANT 392 FT /note="R -> W (in GD; decreased glucosylceramidase FT activity; 5% of normal activity; dbSNP:rs121908308)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032208" FT VARIANT 398 FT /note="R -> Q (in GD1; mild; dbSNP:rs74979486)" FT /evidence="ECO:0000269|PubMed:1487244, FT ECO:0000269|PubMed:8829663" FT /id="VAR_003299" FT VARIANT 400 FT /note="M -> I (in GD2; uncertain significance; FT dbSNP:rs149487315)" FT /evidence="ECO:0000269|PubMed:12204005" FT /id="VAR_032412" FT VARIANT 402 FT /note="Y -> C (in GD; decreased glucosylceramidase FT activity; 8% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs76228122)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032209" FT VARIANT 403 FT /note="S -> T (in GD1; loss of glucosylceramidase activity; FT dbSNP:rs121908307)" FT /evidence="ECO:0000269|PubMed:1899336, FT ECO:0000269|PubMed:8294487" FT /id="VAR_003300" FT VARIANT 405 FT /note="S -> G (in GD)" FT /evidence="ECO:0000269|PubMed:9061570" FT /id="VAR_010067" FT VARIANT 405 FT /note="S -> N (in GD; dbSNP:rs1392291885)" FT /evidence="ECO:0000269|PubMed:9554454" FT /id="VAR_009046" FT VARIANT 405 FT /note="S -> R (in GD1; loss of glucosylceramide catabolic FT process; dbSNP:rs75528494)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081199" FT VARIANT 408 FT /note="T -> M (in GD1; likely benign; dbSNP:rs75548401)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:12694238, ECO:0000269|PubMed:14702039" FT /id="VAR_003301" FT VARIANT 409 FT /note="N -> S (in GD1; risk factor for Parkinson disease; FT increased proteasomal degradation; decreased protein FT abundance; decreased glucosylceramide catabolic process; FT decreased glucosylceramidase activity; 23% of normal FT activity when expressed in a heterologous system; alters FT interaction with saposin-C; dbSNP:rs76763715)" FT /evidence="ECO:0000269|PubMed:10206680, FT ECO:0000269|PubMed:10340647, ECO:0000269|PubMed:10447266, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:15826241, FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:18332251, FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:19846850, FT ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:24022302, FT ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:7915932, FT ECO:0000269|PubMed:8076951, ECO:0000269|PubMed:8294487, FT ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8937765, FT ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9240741, FT ECO:0000269|PubMed:9683600, ECO:0000269|PubMed:9856561, FT ECO:0000269|Ref.14" FT /id="VAR_003302" FT VARIANT 410 FT /note="L -> V (in GD; decreased glucosylceramidase FT activity; 15% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs121908314)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032210" FT VARIANT 414 FT /note="V -> L (in GD and GD1; mild; dbSNP:rs398123528)" FT /evidence="ECO:0000269|PubMed:36776904, FT ECO:0000269|PubMed:9182788" FT /id="VAR_010068" FT VARIANT 416 FT /note="G -> S (in GD1 and GD3; dbSNP:rs121908311)" FT /evidence="ECO:0000269|PubMed:10447266, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:11933202, FT ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:9683600" FT /id="VAR_003303" FT VARIANT 417 FT /note="W -> G (in GD1; dbSNP:rs1450426641)" FT /evidence="ECO:0000269|PubMed:8790604" FT /id="VAR_003304" FT VARIANT 419 FT /note="D -> A (found in a patient with Parkinson disease; FT uncertain significance; dbSNP:rs77284004)" FT /evidence="ECO:0000269|PubMed:19286695" FT /id="VAR_003305" FT VARIANT 419 FT /note="D -> H (in GD; decreased glucosylceramidase FT activity; 4% of normal activity)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032211" FT VARIANT 419 FT /note="D -> N (in GD1; loss of glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302, FT ECO:0000269|PubMed:8790604" FT /id="VAR_003306" FT VARIANT 420 FT /note="W -> C (in GD1; loss of glucosylceramide catabolic FT process)" FT /evidence="ECO:0000269|PubMed:24022302" FT /id="VAR_081200" FT VARIANT 421 FT /note="N -> K (in GD; decreased glucosylceramidase FT activity; 22% of normal activity)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032212" FT VARIANT 426 FT /note="P -> L (in GD; dbSNP:rs1057519357 and FT dbSNP:rs994723035)" FT /evidence="ECO:0000269|PubMed:8937765" FT /id="VAR_010069" FT VARIANT 428 FT /note="G -> E (in GD2)" FT /evidence="ECO:0000269|PubMed:9554746" FT /id="VAR_003307" FT VARIANT 429 FT /note="G -> R (in GD; decreased glucosylceramidase FT activity; 17% of normal activity)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032213" FT VARIANT 430 FT /note="P -> L (in GD1; dbSNP:rs76910485)" FT /evidence="ECO:0000269|PubMed:9554746" FT /id="VAR_003308" FT VARIANT 431 FT /note="N -> I (in GD2; dbSNP:rs77738682)" FT /evidence="ECO:0000269|PubMed:9554746" FT /id="VAR_003309" FT VARIANT 432 FT /note="W -> R (in GD)" FT /evidence="ECO:0000269|PubMed:9554454" FT /id="VAR_009047" FT VARIANT 433 FT /note="V -> L (in GD1 and GD3; severe; decreased FT glucosylceramidase activity; 12% of normal activity; FT dbSNP:rs80356769)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:2508065, FT ECO:0000269|PubMed:8294487, ECO:0000269|PubMed:8937765, FT ECO:0000269|PubMed:9683600" FT /id="VAR_003310" FT VARIANT 435 FT /note="N -> T (in GD1; mild; dbSNP:rs75385858)" FT /evidence="ECO:0000269|PubMed:8889591" FT /id="VAR_003311" FT VARIANT 436 FT /note="F -> S (in GD; decreased glucosylceramidase FT activity; 6% of normal activity; alters protein stability FT and increases susceptibility to proteolytic degradation; FT dbSNP:rs75243000)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032214" FT VARIANT 437 FT /note="V -> F (in GDPL; dbSNP:rs121908310)" FT /evidence="ECO:0000269|PubMed:10352942" FT /id="VAR_009048" FT VARIANT 437 FT /note="V -> L (in GD3; dbSNP:rs121908310)" FT /evidence="ECO:0000269|PubMed:8780099" FT /id="VAR_010070" FT VARIANT 438 FT /note="D -> N (in GD1 and GD2; decreased glucosylceramidase FT activity; 14% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs1553217009)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:8112750, ECO:0000269|PubMed:9856561" FT /id="VAR_003312" FT VARIANT 438 FT /note="D -> Y (in GD1)" FT /evidence="ECO:0000269|PubMed:10796875" FT /id="VAR_032413" FT VARIANT 440 FT /note="P -> L (in GD1; dbSNP:rs74598136)" FT /evidence="ECO:0000269|PubMed:10340647, FT ECO:0000269|PubMed:15605411" FT /id="VAR_010071" FT VARIANT 441 FT /note="I -> F (in GD3)" FT /evidence="ECO:0000269|PubMed:11933202" FT /id="VAR_032414" FT VARIANT 441 FT /note="I -> T (in GD; mild; dbSNP:rs75564605)" FT /evidence="ECO:0000269|PubMed:9182788" FT /id="VAR_010072" FT VARIANT 448 FT /note="D -> H (in GD1, GD2, GD3 and GD3C; associated in cis FT with Q-294 in some patients; at homozygosity it causes FT GD3C; also found in a patient with Parkinson disease; loss FT of glucosylceramidase activity; alters protein stability; FT dbSNP:rs1064651)" FT /evidence="ECO:0000269|PubMed:10360404, FT ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:11992489, FT ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:15605411, FT ECO:0000269|PubMed:15690354, ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:2269438, FT ECO:0000269|PubMed:2508065, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:36776904, ECO:0000269|PubMed:7475546, FT ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:8294487, FT ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:9040001, FT ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9856561" FT /id="VAR_003313" FT VARIANT 448 FT /note="D -> V (in GD3; loss of glucosylceramidase activity; FT results in glycosphingolipid accumulation in brain and FT liver of a knockin mouse model due to impaired FT glucosylceramidase activity; dbSNP:rs77369218)" FT /evidence="ECO:0000269|PubMed:2508065, FT ECO:0000269|PubMed:34106956, ECO:0000269|PubMed:8294487" FT /id="VAR_003314" FT VARIANT 450 FT /note="F -> I (in GD1; dbSNP:rs1553216985)" FT /evidence="ECO:0000269|PubMed:9856561" FT /id="VAR_010073" FT VARIANT 451 FT /note="Y -> H (in GD1)" FT /evidence="ECO:0000269|PubMed:9554746" FT /id="VAR_003315" FT VARIANT 452 FT /note="K -> Q (in GD)" FT /evidence="ECO:0000269|PubMed:9061570" FT /id="VAR_010074" FT VARIANT 454 FT /note="P -> R (in GD2; loss of glucosylceramidase activity; FT dbSNP:rs121908295)" FT /evidence="ECO:0000269|PubMed:2464926, FT ECO:0000269|PubMed:8294487" FT /id="VAR_003316" FT VARIANT 455 FT /note="M -> V (in GD; loss of glucosylceramidase activity; FT increases susceptibility to proteolytic degradation)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032215" FT VARIANT 456 FT /note="F -> V (in GD1; severely decreased FT glucosylceramidase activity; 3% of normal activity when FT expressed in a heterologous system)" FT /evidence="ECO:0000269|PubMed:7915932, FT ECO:0000269|PubMed:9240741" FT /id="VAR_003317" FT VARIANT 457 FT /note="Y -> C (in GD and GD1; dbSNP:rs74752878)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:8076951" FT /id="VAR_003318" FT VARIANT 460 FT /note="G -> D (in GD1; associated in cis with R-490; loss FT of glucosylceramidase activity)" FT /evidence="ECO:0000269|PubMed:15605411" FT /id="VAR_032415" FT VARIANT 464 FT /note="K -> E (in GD3; severe; uncertain significance)" FT /evidence="ECO:0000269|PubMed:1487244" FT /id="VAR_003319" FT VARIANT 482 FT /note="D -> N (likely benign; found in a patient with FT Parkinson disease; dbSNP:rs75671029)" FT /evidence="ECO:0000269|PubMed:19286695" FT /id="VAR_063067" FT VARIANT 483 FT /note="L -> P (in GD1, GD2 and GD3; risk factor for FT Parkinson disease; gene conversion; alters protein FT stability; increased proteasomal degradation; decreased FT protein abundance; very low glucosylceramide catabolic FT process; severe decrease of glucosylceramidase activity; 3% FT of normal activity when expressed in a heterologous system; FT dbSNP:rs421016)" FT /evidence="ECO:0000269|PubMed:10360404, FT ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10679038, FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:15605411, FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:19286695, FT ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:2464926, FT ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:32547927, FT ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:8294487, FT ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:8937765, FT ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9217217, FT ECO:0000269|PubMed:9240741, ECO:0000269|PubMed:9683600, FT ECO:0000269|PubMed:9851895, ECO:0000269|PubMed:9856561" FT /id="VAR_003321" FT VARIANT 483 FT /note="L -> R (in GD1 and GD2; dbSNP:rs421016)" FT /evidence="ECO:0000269|PubMed:27825739, FT ECO:0000269|PubMed:7981693" FT /id="VAR_003320" FT VARIANT 485 FT /note="A -> P (in GD1)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:9683600" FT /id="VAR_003322" FT VARIANT 486 FT /note="V -> E (in GD1)" FT /evidence="ECO:0000269|PubMed:22658918" FT /id="VAR_081201" FT VARIANT 490 FT /note="H -> R (in GD1; associated in cis with D-460; FT uncertain significance; no effect on glucosylceramidase FT activity; dbSNP:rs76071730)" FT /evidence="ECO:0000269|PubMed:12204005, FT ECO:0000269|PubMed:15605411" FT /id="VAR_032416" FT VARIANT 495 FT /note="A -> P (in GD1; loss of glucosylceramidase activity; FT dbSNP:rs368060)" FT /evidence="ECO:0000269|PubMed:19286695, FT ECO:0000269|PubMed:27825739, ECO:0000269|PubMed:8294487" FT /id="VAR_003323" FT VARIANT 497 FT /note="V -> L" FT /evidence="ECO:0000269|PubMed:19286695" FT /id="VAR_063068" FT VARIANT 500 FT /note="L -> P (in GD; decreased glucosylceramidase FT activity; 10% of normal activity; increases susceptibility FT to proteolytic degradation; dbSNP:rs1362103320)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032216" FT VARIANT 501 FT /note="N -> K (in GD2)" FT /evidence="ECO:0000269|PubMed:9279145" FT /id="VAR_009049" FT VARIANT 501 FT /note="N -> Y (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088444" FT VARIANT 502 FT /note="R -> C (in GD1 and GD2; also found in patients with FT Parkinson disease; no effect on protein abundance; FT decreased glucosylceramidase activity; dbSNP:rs80356771)" FT /evidence="ECO:0000269|PubMed:10796875, FT ECO:0000269|PubMed:1301953, ECO:0000269|PubMed:16293621, FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:1972019, FT ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:8294487, FT ECO:0000269|PubMed:8598642, ECO:0000269|PubMed:9683600" FT /id="VAR_003324" FT VARIANT 502 FT /note="R -> P (in GD; loss of glucosylceramidase activity; FT increases susceptibility to proteolytic degradation)" FT /evidence="ECO:0000269|PubMed:16293621" FT /id="VAR_032217" FT VARIANT 509 FT /note="L -> P" FT /id="VAR_003325" FT VARIANT 513 FT /note="D -> Y (in GD2)" FT /evidence="ECO:0000269|PubMed:9637431" FT /id="VAR_009050" FT VARIANT 517 FT /note="G -> S (in GD; dbSNP:rs121908301)" FT /evidence="ECO:0000269|PubMed:8432537" FT /id="VAR_003326" FT VARIANT 521 FT /note="T -> K (in GD1)" FT /evidence="ECO:0000269|PubMed:32547927" FT /id="VAR_088445" FT VARIANT 530 FT /note="T -> I (in GD3; dbSNP:rs78016673)" FT /evidence="ECO:0000269|PubMed:8780099" FT /id="VAR_010075" FT VARIANT 535 FT /note="R -> C (in GD1; mild; dbSNP:rs747506979)" FT /evidence="ECO:0000269|PubMed:1487244, FT ECO:0000269|PubMed:32547927, ECO:0000269|PubMed:9061570" FT /id="VAR_003327" FT VARIANT 535 FT /note="R -> H (in GD1; decreased glucosylceramidase FT activity; 7% of normal activity when expressed in a FT heterologous system; dbSNP:rs75822236)" FT /evidence="ECO:0000269|PubMed:7916532, FT ECO:0000269|PubMed:8432537, ECO:0000269|PubMed:9240741" FT /id="VAR_003328" FT MUTAGEN 43 FT /note="C->S: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:16293621" FT MUTAGEN 57 FT /note="C->S: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:16293621" FT MUTAGEN 62 FT /note="C->S: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:16293621" FT MUTAGEN 379 FT /note="E->G: 1000-fold decreases of glucosylceramidase FT activity." FT /evidence="ECO:0000269|PubMed:7908905" FT MUTAGEN 482 FT /note="D->E: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:8294487" FT MUTAGEN 482 FT /note="D->G: Decreased glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:8294487" FT MUTAGEN 482 FT /note="D->S: Severe decrease of glucosylceramidase FT activity." FT /evidence="ECO:0000269|PubMed:8294487" FT MUTAGEN 501 FT /note="N->D: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:8294487" FT MUTAGEN 501 FT /note="N->Q: Loss of glucosylceramidase activity." FT /evidence="ECO:0000269|PubMed:8294487" FT CONFLICT 176 FT /note="D -> G (in Ref. 7; BAH13357)" FT /evidence="ECO:0000305" FT CONFLICT 227 FT /note="N -> R (in Ref. 5; BAA02546)" FT /evidence="ECO:0000305" FT CONFLICT 470 FT /note="S -> I (in Ref. 15; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 534 FT /note="R -> H (in Ref. 1; AAA35873)" FT /evidence="ECO:0000305" FT STRAND 44..46 FT /evidence="ECO:0007829|PDB:6Q1P" FT STRAND 49..52 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 54..57 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 75..82 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 88..94 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 103..116 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 119..123 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 126..133 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 137..148 FT /evidence="ECO:0007829|PDB:6Q6N" FT TURN 150..153 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 157..163 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:6Q6K" FT HELIX 190..194 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 196..206 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 212..218 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 222..224 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:6Q1N" FT STRAND 228..233 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 243..261 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 267..271 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 275..279 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 284..286 FT /evidence="ECO:0007829|PDB:3GXF" FT HELIX 292..301 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 303..308 FT /evidence="ECO:0007829|PDB:6Q6N" FT TURN 311..314 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 315..323 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 324..326 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 329..335 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 346..350 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 354..356 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 359..369 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 373..380 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 385..388 FT /evidence="ECO:0007829|PDB:6MOZ" FT HELIX 396..411 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 414..422 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 426..428 FT /evidence="ECO:0007829|PDB:3KEH" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:6Q1N" FT STRAND 440..444 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 445..447 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 449..452 FT /evidence="ECO:0007829|PDB:6Q6N" FT HELIX 454..463 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 471..479 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 482..489 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 495..501 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 503..505 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 507..513 FT /evidence="ECO:0007829|PDB:6Q6N" FT TURN 514..516 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 517..523 FT /evidence="ECO:0007829|PDB:6Q6N" FT STRAND 527..533 FT /evidence="ECO:0007829|PDB:6Q6N" SQ SEQUENCE 536 AA; 59716 MW; FA1E15684344A0E6 CRC64; MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT YCDSFDPPTF PALGTFSRYE STRSGRRMEL SMGPIQANHT GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV PMASCDFSIR TYTYADTPDD FQLHNFSLPE EDTKLKIPLI HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA RDLGPTLANS THHNVRLLML DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM QYSHSIITNL LYHVVGWTDW NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK NDLDAVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ //