ID G6PC3_HUMAN Reviewed; 346 AA. AC Q9BUM1; Q8WU15; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2004, sequence version 2. DT 27-MAR-2024, entry version 174. DE RecName: Full=Glucose-6-phosphatase 3; DE Short=G-6-Pase 3; DE Short=G6Pase 3; DE EC=3.1.3.9; DE AltName: Full=Glucose-6-phosphatase beta; DE Short=G6Pase-beta; DE AltName: Full=Ubiquitous glucose-6-phosphatase catalytic subunit-related protein; GN Name=G6PC3; Synonyms=UGRP; 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 [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye, and Skin; 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 [3] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=12370122; DOI=10.1677/jme.0.0290205; RA Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I., Hutton J.C., RA O'Brien R.M.; RT "Identification and characterization of a human cDNA and gene encoding a RT ubiquitously expressed glucose-6-phosphatase catalytic subunit-related RT protein."; RL J. Mol. Endocrinol. 29:205-222(2002). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE RP SPECIFICITY. RX PubMed=12965222; DOI=10.1016/s0014-5793(03)00903-7; RA Guionie O., Clottes E., Stafford K., Burchell A.; RT "Identification and characterisation of a new human glucose-6-phosphatase RT isoform."; RL FEBS Lett. 551:159-164(2003). RN [5] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF ARG-79; HIS-114 AND HIS-167. RX PubMed=13129915; DOI=10.1074/jbc.m309472200; RA Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y.; RT "A glucose-6-phosphate hydrolase, widely expressed outside the liver, can RT explain age-dependent resolution of hypoglycemia in glycogen storage RT disease type Ia."; RL J. Biol. Chem. 278:47098-47103(2003). RN [6] RP TOPOLOGY, AND ACTIVE SITE. RX PubMed=14718531; DOI=10.1074/jbc.m313271200; RA Ghosh A., Shieh J.-J., Pan C.-J., Chou J.Y.; RT "Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-beta RT forming a phosphohistidine enzyme intermediate during catalysis."; RL J. Biol. Chem. 279:12479-12483(2004). RN [7] RP TISSUE SPECIFICITY. RX PubMed=14765991; DOI=10.1677/jme.0.0320033; RA Boustead J.N., Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I., RA Hutton J.C., O'Brien R.M.; RT "Identification and characterization of a cDNA and the gene encoding the RT mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit- RT related protein."; RL J. Mol. Endocrinol. 32:33-53(2004). RN [8] RP VARIANTS SCN4 PRO-185; HIS-253 AND ARG-262, AND CHARACTERIZATION OF VARIANT RP SCN4 HIS-253. RX PubMed=19118303; DOI=10.1056/nejmoa0805051; RA Boztug K., Appaswamy G., Ashikov A., Schaeffer A.A., Salzer U., RA Diestelhorst J., Germeshausen M., Brandes G., Lee-Gossler J., Noyan F., RA Gatzke A.-K., Minkov M., Greil J., Kratz C., Petropoulou T., Pellier I., RA Bellanne-Chantelot C., Rezaei N., Moenkemoeller K., Irani-Hakimeh N., RA Bakker H., Gerardy-Schahn R., Zeidler C., Grimbacher B., Welte K., RA Klein C.; RT "A syndrome with congenital neutropenia and mutations in G6PC3."; RL N. Engl. J. Med. 360:32-43(2009). RN [9] RP VARIANT DURSS VAL-116. RX PubMed=20799326; DOI=10.1002/ajmg.a.33615; RA Banka S., Newman W.G., Ozgul R.K., Dursun A.; RT "Mutations in the G6PC3 gene cause Dursun syndrome."; RL Am. J. Med. Genet. A 152:2609-2611(2010). RN [10] RP VARIANT SCN4 ARG-260, AND CHARACTERIZATION OF VARIANT SCN4 ARG-260. RX PubMed=20616219; DOI=10.1182/blood-2010-01-265942; RA McDermott D.H., De Ravin S.S., Jun H.S., Liu Q., Priel D.A., Noel P., RA Takemoto C.M., Ojode T., Paul S.M., Dunsmore K.P., Hilligoss D., RA Marquesen M., Ulrick J., Kuhns D.B., Chou J.Y., Malech H.L., Murphy P.M.; RT "Severe congenital neutropenia resulting from G6PC3 deficiency with RT increased neutrophil CXCR4 expression and myelokathexis."; RL Blood 116:2793-2802(2010). RN [11] RP VARIANTS SCN4 LYS-116; GLN-189 AND ARG-260. RX PubMed=20220065; DOI=10.3324/haematol.2009.017665; RA Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M., RA Welte K.; RT "Digenic mutations in severe congenital neutropenia."; RL Haematologica 95:1207-1210(2010). RN [12] RP VARIANTS SCN4 SER-44; 64-THR--ILE-70 DEL AND ARG-208, AND CHARACTERIZATION RP OF VARIANTS SCN4 SER-44 AND 64-THR--ILE-70 DEL. RX PubMed=22469094; DOI=10.1111/j.1365-2141.2012.09110.x; RA Smith B.N., Evans C., Ali A., Ancliff P.J., Hayee B., Segal A.W., Hall G., RA Kaya Z., Shakoori A.R., Linch D.C., Gale R.E.; RT "Phenotypic heterogeneity and evidence of a founder effect associated with RT G6PC3 mutations in patients with severe congenital neutropenia."; RL Br. J. Haematol. 158:146-149(2012). RN [13] RP VARIANTS SCN4 LEU-44; LYS-116; ILE-139; GLN-161; HIS-253; ARG-260 AND RP ASP-260. RX PubMed=22050868; DOI=10.1016/j.jpeds.2011.09.019; RA Boztug K., Rosenberg P.S., Dorda M., Banka S., Moulton T., Curtin J., RA Rezaei N., Corns J., Innis J.W., Avci Z., Tran H.C., Pellier I., RA Pierani P., Fruge R., Parvaneh N., Mamishi S., Mody R., Darbyshire P., RA Motwani J., Murray J., Buchanan G.R., Newman W.G., Alter B.P., Boxer L.A., RA Donadieu J., Welte K., Klein C.; RT "Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 RT deficiency: novel genotypes and phenotypic variability in severe congenital RT neutropenia."; RL J. Pediatr. 160:679-683(2012). RN [14] RP VARIANT SCN4 ARG-325. RX PubMed=24105461; DOI=10.1007/s10875-013-9945-7; RA Alangari A.A., Alsultan A., Osman M.E., Anazi S., Alkuraya F.S.; RT "A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and RT severe congenital neutropenia in the same family."; RL J. Clin. Immunol. 33:1403-1406(2013). RN [15] RP VARIANTS SCN4 SER-44; THR-116 AND CYS-253. RX PubMed=23298686; DOI=10.1016/j.ymgme.2012.12.001; RA Banka S., Wynn R., Byers H., Arkwright P.D., Newman W.G.; RT "G6PC3 mutations cause non-syndromic severe congenital neutropenia."; RL Mol. Genet. Metab. 108:138-141(2013). RN [16] RP VARIANT SCN4 PRO-154. RX PubMed=23018568; DOI=10.1097/mph.0b013e3182679000; RA Aytekin C., Germeshausen M., Tuygun N., Dogu F., Ikinciogullari A.; RT "A novel G6PC3 gene mutation in a patient with severe congenital RT neutropenia."; RL J. Pediatr. Hematol. Oncol. 35:E81-E83(2013). RN [17] RP VARIANT SCN4 ARG-59. RX PubMed=24750412; DOI=10.1111/ejh.12349; RA Arikoglu T., Kuyucu N., Germeshausen M., Kuyucu S.; RT "A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia RT and variable bone marrow phenotype can also be part of this syndrome."; RL Eur. J. Haematol. 94:79-82(2015). RN [18] RP CHARACTERIZATION OF VARIANTS SCN4 LEU-44; SER-44; ILE-116; LYS-116; RP THR-116; VAL-116; ARG-118; ILE-139; PRO-154; GLN-161; PRO-185; GLN-189; RP ARG-208; HIS-253; ARG-260 AND ASP-260. RX PubMed=25492228; DOI=10.1016/j.ymgme.2014.11.012; RA Lin S.R., Pan C.J., Mansfield B.C., Chou J.Y.; RT "Functional analysis of mutations in a severe congenital neutropenia RT syndrome caused by glucose-6-phosphatase-beta deficiency."; RL Mol. Genet. Metab. 114:41-45(2015). CC -!- FUNCTION: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic CC reticulum. May form with the glucose-6-phosphate transporter CC (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose CC production through glycogenolysis and gluconeogenesis. Probably CC required for normal neutrophil function. {ECO:0000269|PubMed:12370122, CC ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915}. CC -!- CATALYTIC ACTIVITY: CC Reaction=D-glucose 6-phosphate + H2O = D-glucose + phosphate; CC Xref=Rhea:RHEA:16689, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:61548; EC=3.1.3.9; CC Evidence={ECO:0000269|PubMed:12965222}; CC -!- ACTIVITY REGULATION: Inhibited by vanadate. CC {ECO:0000269|PubMed:13129915}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1 mM for glucose-6-phosphate (at pH 5.5) CC {ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915}; CC KM=2 mM for glucose-6-phosphate (at pH 6.5) CC {ECO:0000269|PubMed:12965222, ECO:0000269|PubMed:13129915}; CC Note=8 times less active compared to G6PC1 under the same CC experimental conditions.; CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:13129915}; Multi-pass membrane protein CC {ECO:0000269|PubMed:13129915}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highly expressed in CC skeletal muscle, at intermediate levels in heart, brain, placenta, CC kidney, colon, thymus, spleen and pancreas. Also detected in testis, CC prostate, ovary, liver, lung, small intestine and peripheral blood CC lymphocytes. {ECO:0000269|PubMed:12370122, ECO:0000269|PubMed:12965222, CC ECO:0000269|PubMed:14765991}. CC -!- DISEASE: Neutropenia, severe congenital 4, autosomal recessive (SCN4) CC [MIM:612541]: A disorder of hematopoiesis characterized by maturation CC arrest of granulopoiesis at the level of promyelocytes with peripheral CC blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of CC severe bacterial infections. {ECO:0000269|PubMed:19118303, CC ECO:0000269|PubMed:20220065, ECO:0000269|PubMed:20616219, CC ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:22469094, CC ECO:0000269|PubMed:23018568, ECO:0000269|PubMed:23298686, CC ECO:0000269|PubMed:24105461, ECO:0000269|PubMed:24750412, CC ECO:0000269|PubMed:25492228}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Dursun syndrome (DURSS) [MIM:612541]: A disease characterized CC by pulmonary arterial hypertension, cardiac abnormalities including CC secundum-type atrial septal defect, intermittent neutropenia, CC lymphopenia, monocytosis and anemia. {ECO:0000269|PubMed:20799326}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the glucose-6-phosphatase family. {ECO:0000305}. CC -!- CAUTION: According to PubMed:12370122, it has no hydrolytic activity. CC {ECO:0000305}. 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; CH471178; EAW51638.1; -; Genomic_DNA. DR EMBL; BC002494; AAH02494.2; -; mRNA. DR EMBL; BC021574; AAH21574.1; -; mRNA. DR CCDS; CCDS11476.1; -. DR RefSeq; NP_612396.1; NM_138387.3. DR AlphaFoldDB; Q9BUM1; -. DR SMR; Q9BUM1; -. DR BioGRID; 124957; 16. DR IntAct; Q9BUM1; 5. DR MINT; Q9BUM1; -. DR STRING; 9606.ENSP00000269097; -. DR DEPOD; G6PC3; -. DR iPTMnet; Q9BUM1; -. DR PhosphoSitePlus; Q9BUM1; -. DR SwissPalm; Q9BUM1; -. DR BioMuta; G6PC3; -. DR DMDM; 74733234; -. DR EPD; Q9BUM1; -. DR jPOST; Q9BUM1; -. DR MassIVE; Q9BUM1; -. DR MaxQB; Q9BUM1; -. DR PaxDb; 9606-ENSP00000269097; -. DR PeptideAtlas; Q9BUM1; -. DR ProteomicsDB; 79110; -. DR Pumba; Q9BUM1; -. DR Antibodypedia; 59289; 98 antibodies from 18 providers. DR DNASU; 92579; -. DR Ensembl; ENST00000269097.9; ENSP00000269097.3; ENSG00000141349.10. DR GeneID; 92579; -. DR KEGG; hsa:92579; -. DR MANE-Select; ENST00000269097.9; ENSP00000269097.3; NM_138387.4; NP_612396.1. DR UCSC; uc002iex.4; human. DR AGR; HGNC:24861; -. DR CTD; 92579; -. DR DisGeNET; 92579; -. DR GeneCards; G6PC3; -. DR GeneReviews; G6PC3; -. DR HGNC; HGNC:24861; G6PC3. DR HPA; ENSG00000141349; Low tissue specificity. DR MalaCards; G6PC3; -. DR MIM; 611045; gene. DR MIM; 612541; phenotype. DR neXtProt; NX_Q9BUM1; -. DR OpenTargets; ENSG00000141349; -. DR Orphanet; 331176; Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency. DR PharmGKB; PA134968446; -. DR VEuPathDB; HostDB:ENSG00000141349; -. DR eggNOG; ENOG502QS5D; Eukaryota. DR GeneTree; ENSGT00950000183150; -. DR InParanoid; Q9BUM1; -. DR OMA; KKWCSRA; -. DR OrthoDB; 4030642at2759; -. DR PhylomeDB; Q9BUM1; -. DR TreeFam; TF324388; -. DR BioCyc; MetaCyc:HS13873-MONOMER; -. DR BRENDA; 3.1.3.9; 2681. DR PathwayCommons; Q9BUM1; -. DR Reactome; R-HSA-3282872; Severe congenital neutropenia type 4 (G6PC3). DR Reactome; R-HSA-70263; Gluconeogenesis. DR SABIO-RK; Q9BUM1; -. DR SignaLink; Q9BUM1; -. DR SIGNOR; Q9BUM1; -. DR UniPathway; UPA00138; -. DR BioGRID-ORCS; 92579; 11 hits in 1171 CRISPR screens. DR ChiTaRS; G6PC3; human. DR GeneWiki; G6PC3; -. DR GenomeRNAi; 92579; -. DR Pharos; Q9BUM1; Tbio. DR PRO; PR:Q9BUM1; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9BUM1; Protein. DR Bgee; ENSG00000141349; Expressed in adenohypophysis and 194 other cell types or tissues. DR ExpressionAtlas; Q9BUM1; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0004346; F:glucose-6-phosphatase activity; IMP:UniProtKB. DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central. DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IBA:GO_Central. DR GO; GO:0015760; P:glucose-6-phosphate transport; IEA:Ensembl. DR CDD; cd03381; PAP2_glucose_6_phosphatase; 1. DR Gene3D; 1.20.144.10; Phosphatidic acid phosphatase type 2/haloperoxidase; 1. DR InterPro; IPR016275; Glucose-6-phosphatase. DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf. DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase. DR PANTHER; PTHR12591; GLUCOSE-6-PHOSPHATASE; 1. DR PANTHER; PTHR12591:SF2; GLUCOSE-6-PHOSPHATASE 3; 1. DR Pfam; PF01569; PAP2; 1. DR PIRSF; PIRSF000905; Glucose-6-phosphatase; 1. DR SMART; SM00014; acidPPc; 1. DR SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 1. DR Genevisible; Q9BUM1; HS. PE 1: Evidence at protein level; KW Disease variant; Endoplasmic reticulum; Gluconeogenesis; Hydrolase; KW Membrane; Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..346 FT /note="Glucose-6-phosphatase 3" FT /id="PRO_0000334512" FT TOPO_DOM 1..24 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 25..45 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 46..54 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 55..75 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 76..114 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 115..135 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 136..146 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 147..164 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 165..169 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 170..186 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 187..197 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 198..218 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 219..254 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 255..273 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 274..283 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 284..304 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 305..307 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 308..328 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 329..346 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT ACT_SITE 114 FT /note="Proton donor" FT /evidence="ECO:0000255" FT ACT_SITE 167 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:14718531" FT BINDING 79 FT /ligand="substrate" FT /evidence="ECO:0000255" FT BINDING 161 FT /ligand="substrate" FT /evidence="ECO:0000255" FT VARIANT 44 FT /note="P -> L (in SCN4; complete loss of activity; FT dbSNP:rs762019955)" FT /evidence="ECO:0000269|PubMed:22050868, FT ECO:0000269|PubMed:25492228" FT /id="VAR_073174" FT VARIANT 44 FT /note="P -> S (in SCN4; complete loss of activity; purified FT neutrophils from patients have higher levels of spontaneous FT and staurosporine-induced apoptosis than controls; FT dbSNP:rs775224457)" FT /evidence="ECO:0000269|PubMed:22469094, FT ECO:0000269|PubMed:23298686, ECO:0000269|PubMed:25492228" FT /id="VAR_072753" FT VARIANT 59 FT /note="W -> R (in SCN4; dbSNP:rs752966267)" FT /evidence="ECO:0000269|PubMed:24750412" FT /id="VAR_072754" FT VARIANT 64..70 FT /note="Missing (in SCN4; purified neutrophils from patients FT have higher levels of spontaneous and staurosporine-induced FT apoptosis than controls)" FT /evidence="ECO:0000269|PubMed:22469094" FT /id="VAR_072755" FT VARIANT 116 FT /note="M -> I (in SCN4; complete loss of activity; FT dbSNP:rs1373865222)" FT /evidence="ECO:0000269|PubMed:25492228" FT /id="VAR_073175" FT VARIANT 116 FT /note="M -> K (in SCN4; the patient also carries mutation FT Thr-166 in ELANE; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:20220065, FT ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:25492228" FT /id="VAR_064508" FT VARIANT 116 FT /note="M -> T (in SCN4; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:23298686, FT ECO:0000269|PubMed:25492228" FT /id="VAR_072756" FT VARIANT 116 FT /note="M -> V (in DURSS and SCN4; complete loss of FT activity; dbSNP:rs267606834)" FT /evidence="ECO:0000269|PubMed:20799326, FT ECO:0000269|PubMed:25492228" FT /id="VAR_064509" FT VARIANT 118 FT /note="T -> R (in SCN4; complete loss of activity; FT dbSNP:rs766706036)" FT /evidence="ECO:0000269|PubMed:25492228" FT /id="VAR_073176" FT VARIANT 139 FT /note="S -> I (in SCN4; partial loss of activity)" FT /evidence="ECO:0000269|PubMed:22050868, FT ECO:0000269|PubMed:25492228" FT /id="VAR_072757" FT VARIANT 154 FT /note="L -> P (in SCN4; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:23018568, FT ECO:0000269|PubMed:25492228" FT /id="VAR_072758" FT VARIANT 161 FT /note="R -> Q (in SCN4; complete loss of activity; FT dbSNP:rs1485073209)" FT /evidence="ECO:0000269|PubMed:22050868, FT ECO:0000269|PubMed:25492228" FT /id="VAR_073177" FT VARIANT 185 FT /note="L -> P (in SCN4; complete loss of activity; FT dbSNP:rs118203969)" FT /evidence="ECO:0000269|PubMed:19118303, FT ECO:0000269|PubMed:25492228" FT /id="VAR_055156" FT VARIANT 189 FT /note="R -> Q (in SCN4; partial loss of activity; FT dbSNP:rs140294222)" FT /evidence="ECO:0000269|PubMed:20220065, FT ECO:0000269|PubMed:25492228" FT /id="VAR_064510" FT VARIANT 208 FT /note="L -> R (in SCN4; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:22469094, FT ECO:0000269|PubMed:25492228" FT /id="VAR_072759" FT VARIANT 216 FT /note="T -> I (in dbSNP:rs34406052)" FT /id="VAR_043378" FT VARIANT 253 FT /note="R -> C (in SCN4; dbSNP:rs765927570)" FT /evidence="ECO:0000269|PubMed:23298686" FT /id="VAR_073178" FT VARIANT 253 FT /note="R -> H (in SCN4; complete loss of activity; FT peripheral-blood patient neutrophils have an increased rate FT of spontaneous apoptosis; transmission electron microscopy FT of patient bone marrow cells shows an enlarged rough FT endoplasmic reticulum in myeloid progenitor cells FT consistent with increased ER stress; dbSNP:rs118203968)" FT /evidence="ECO:0000269|PubMed:19118303, FT ECO:0000269|PubMed:22050868, ECO:0000269|PubMed:25492228" FT /id="VAR_055157" FT VARIANT 260 FT /note="G -> D (in SCN4; complete loss of activity)" FT /evidence="ECO:0000269|PubMed:22050868, FT ECO:0000269|PubMed:25492228" FT /id="VAR_072760" FT VARIANT 260 FT /note="G -> R (in SCN4; complete loss of activity; FT dbSNP:rs200478425)" FT /evidence="ECO:0000269|PubMed:20220065, FT ECO:0000269|PubMed:20616219, ECO:0000269|PubMed:22050868, FT ECO:0000269|PubMed:25492228" FT /id="VAR_064511" FT VARIANT 262 FT /note="G -> R (in SCN4; dbSNP:rs118203971)" FT /evidence="ECO:0000269|PubMed:19118303" FT /id="VAR_055158" FT VARIANT 325 FT /note="L -> R (in SCN4)" FT /evidence="ECO:0000269|PubMed:24105461" FT /id="VAR_072761" FT MUTAGEN 79 FT /note="R->A: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:13129915" FT MUTAGEN 114 FT /note="H->A: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:13129915" FT MUTAGEN 167 FT /note="H->A: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:13129915" SQ SEQUENCE 346 AA; 38735 MW; 55C1F322E59C8439 CRC64; MESTLGAGIV IAEALQNQLA WLENVWLWIT FLGDPKILFL FYFPAAYYAS RRVGIAVLWI SLITEWLNLI FKWFLFGDRP FWWVHESGYY SQAPAQVHQF PSSCETGPGS PSGHCMITGA ALWPIMTALS SQVATRARSR WVRVMPSLAY CTFLLAVGLS RIFILAHFPH QVLAGLITGA VLGWLMTPRV PMERELSFYG LTALALMLGT SLIYWTLFTL GLDLSWSISL AFKWCERPEW IHVDSRPFAS LSRDSGAALG LGIALHSPCY AQVRRAQLGN GQKIACLVLA MGLLGPLDWL GHPPQISLFY IFNFLKYTLW PCLVLALVPW AVHMFSAQEA PPIHSS //