ID LDLR_HUMAN Reviewed; 860 AA. AC P01130; B4DII3; B4DJZ8; B4DR00; B4DTQ3; C0JYY8; H0YLU8; H0YNT7; Q53ZD9; AC Q59FQ1; Q9UDH7; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 265. DE RecName: Full=Low-density lipoprotein receptor; DE Short=LDL receptor; DE Flags: Precursor; GN Name=LDLR; 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 1), SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=6091915; DOI=10.1016/0092-8674(84)90188-0; RA Yamamoto T., Davis C.G., Brown M.S., Schneider W.J., Casey M.L., RA Goldstein J.L., Russell D.W.; RT "The human LDL receptor: a cysteine-rich protein with multiple Alu RT sequences in its mRNA."; RL Cell 39:27-38(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2988123; DOI=10.1126/science.2988123; RA Suedhof T.C., Goldstein J.L., Brown M.S., Russell D.W.; RT "The LDL receptor gene: a mosaic of exons shared with different proteins."; RL Science 228:815-822(1985). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RA Jia S., Lv L., Sun H., Wang Q., Wang H., Zhan L., Yang Z.; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6). RC TISSUE=Hippocampus, Placenta, and Thalamus; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., RA Toth E.J., Krauss R.M., Nickerson D.A.; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [10] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; 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 [12] RP PROTEIN SEQUENCE OF 186-210; 394-405; 441-449; 472-495; 521-541 AND RP 605-617. RC TISSUE=Cervix carcinoma; RX PubMed=8127891; DOI=10.1073/pnas.91.5.1839; RA Hofer F., Gruenberger M., Kowalski H., Machat H., Huettinger M., RA Kuechler E., Blaas D.; RT "Members of the low density lipoprotein receptor family mediate cell entry RT of a minor-group common cold virus."; RL Proc. Natl. Acad. Sci. U.S.A. 91:1839-1842(1994). RN [13] RP FUNCTION, AND GLYCOSYLATION. RX PubMed=3005267; DOI=10.1016/s0021-9258(17)35862-3; RA Davis C.G., Elhammer A., Russell D.W., Schneider W.J., Kornfeld S., RA Brown M.S., Goldstein J.L.; RT "Deletion of clustered O-linked carbohydrates does not impair function of RT low density lipoprotein receptor in transfected fibroblasts."; RL J. Biol. Chem. 261:2828-2838(1986). RN [14] RP MUTAGENESIS OF CYTOPLASMIC DOMAIN, AND SUBCELLULAR LOCATION. RX PubMed=3104336; DOI=10.1016/s0021-9258(18)61313-4; RA Davis C.G., van Driel I.R., Russell D.W., Brown M.S., Goldstein J.L.; RT "The low density lipoprotein receptor. Identification of amino acids in RT cytoplasmic domain required for rapid endocytosis."; RL J. Biol. Chem. 262:4075-4082(1987). RN [15] RP FUNCTION (MICROBIAL INFECTION) AS RECEPTOR OF HEPATITIS C VIRUS. RX PubMed=10535997; DOI=10.1073/pnas.96.22.12766; RA Agnello V., Abel G., Elfahal M., Knight G.B., Zhang Q.X.; RT "Hepatitis C virus and other flaviviridae viruses enter cells via low RT density lipoprotein receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 96:12766-12771(1999). RN [16] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 TAT. RX PubMed=11100124; DOI=10.1038/82199; RA Liu Y., Jones M., Hingtgen C.M., Bu G., Laribee N., Tanzi R.E., Moir R.D., RA Nath A., He J.J.; RT "Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor- RT related protein disrupts the neuronal metabolic balance of the receptor RT ligands."; RL Nat. Med. 6:1380-1387(2000). RN [17] RP INTERACTION WITH LDLRAP1. RX PubMed=12221107; DOI=10.1074/jbc.m208539200; RA He G., Gupta S., Yi M., Michaely P., Hobbs H.H., Cohen J.C.; RT "ARH is a modular adaptor protein that interacts with the LDL receptor, RT clathrin, and AP-2."; RL J. Biol. Chem. 277:44044-44049(2002). RN [18] RP INTERACTION WITH ARRB1, AND MUTAGENESIS OF TYR-828 AND SER-854. RX PubMed=12944399; DOI=10.1074/jbc.m309450200; RA Wu J.-H., Peppel K., Nelson C.D., Lin F.-T., Kohout T.A., Miller W.E., RA Exum S.T., Freedman N.J.; RT "The adaptor protein beta-arrestin2 enhances endocytosis of the low density RT lipoprotein receptor."; RL J. Biol. Chem. 278:44238-44245(2003). RN [19] RP GLYCOSYLATION AT ASN-657. 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 [20] RP FUNCTION (MICROBIAL INFECTION) AS RECEPTOR OF HEPATITIS C VIRUS. RX PubMed=12615904; DOI=10.1084/jem.20021756; RA Bartosch B., Dubuisson J., Cosset F.-L.; RT "Infectious hepatitis C virus pseudo-particles containing functional E1-E2 RT envelope protein complexes."; RL J. Exp. Med. 197:633-642(2003). RN [21] RP INTERACTION WITH SNX17. RX PubMed=14739284; DOI=10.1074/jbc.m313689200; RA Burden J.J., Sun X.-M., Garcia Garcia A.B., Soutar A.K.; RT "Sorting motifs in the intracellular domain of the low density lipoprotein RT receptor interact with a novel domain of sorting nexin-17."; RL J. Biol. Chem. 279:16237-16245(2004). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [24] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PCSK9. RX PubMed=17461796; DOI=10.1111/j.1600-0854.2007.00562.x; RA Nassoury N., Blasiole D.A., Tebon Oler A., Benjannet S., Hamelin J., RA Poupon V., McPherson P.S., Attie A.D., Prat A., Seidah N.G.; RT "The cellular trafficking of the secretory proprotein convertase PCSK9 and RT its dependence on the LDLR."; RL Traffic 8:718-732(2007). RN [25] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-657. 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 [26] RP SUBCELLULAR LOCATION, GLYCOSYLATION, CHARACTERIZATION OF VARIANT SAINT OMER RP ASP-546, MUTAGENESIS OF LYS-811; LYS-816; LYS-830 AND CYS-839, RP UBIQUITINATION, AND REGION. RX PubMed=19520913; DOI=10.1126/science.1168974; RA Zelcer N., Hong C., Boyadjian R., Tontonoz P.; RT "LXR regulates cholesterol uptake through Idol-dependent ubiquitination of RT the LDL receptor."; RL Science 325:100-104(2009). RN [27] 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 [28] RP INTERACTION WITH PCSK9. RX PubMed=21149300; DOI=10.1074/jbc.m110.199042; RA Yamamoto T., Lu C., Ryan R.O.; RT "A two-step binding model of PCSK9 interaction with the low density RT lipoprotein receptor."; RL J. Biol. Chem. 286:5464-5470(2011). RN [29] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH VESICULAR STOMATITIS RP VIRUS GLYCOPROTEIN. RX PubMed=23589850; DOI=10.1073/pnas.1214441110; RA Finkelshtein D., Werman A., Novick D., Barak S., Rubinstein M.; RT "LDL receptor and its family members serve as the cellular receptors for RT vesicular stomatitis virus."; RL Proc. Natl. Acad. Sci. U.S.A. 110:7306-7311(2013). RN [30] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [32] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PGRMC1 AND TMEM97. RX PubMed=30443021; DOI=10.1038/s41598-018-35430-3; RA Riad A., Zeng C., Weng C.C., Winters H., Xu K., Makvandi M., Metz T., RA Carlin S., Mach R.H.; RT "Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization RT of LDL by LDL Receptor through the Formation of a Ternary Complex."; RL Sci. Rep. 8:16845-16845(2018). RN [33] RP INTERACTION WITH C.DIFFICILE TCDA (MICROBIAL INFECTION). RX PubMed=31160825; DOI=10.1038/s41564-019-0464-z; RA Tao L., Tian S., Zhang J., Liu Z., Robinson-McCarthy L., Miyashita S.I., RA Breault D.T., Gerhard R., Oottamasathien S., Whelan S.P.J., Dong M.; RT "Sulfated glycosaminoglycans and low-density lipoprotein receptor RT contribute to Clostridium difficile toxin A entry into cells."; RL Nat. Microbiol. 4:1760-1769(2019). RN [34] RP STRUCTURE BY NMR OF 20-67. RX PubMed=7603991; DOI=10.1073/pnas.92.14.6334; RA Daly N.L., Scanlon M.J., Djordjevic J.T., Kroon P.A., Smith R.; RT "Three-dimensional structure of a cysteine-rich repeat from the low-density RT lipoprotein receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 92:6334-6338(1995). RN [35] RP STRUCTURE BY NMR OF 65-104. RX PubMed=7578052; DOI=10.1021/bi00044a025; RA Daly N.L., Djordjevic J.T., Kroon P.A., Smith R.; RT "Three-dimensional structure of the second cysteine-rich repeat from the RT human low-density lipoprotein receptor."; RL Biochemistry 34:14474-14481(1995). RN [36] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 196-232. RX PubMed=9262405; DOI=10.1038/41798; RA Fass D., Blacklow S.C., Kim P.S., Berger J.M.; RT "Molecular basis of familial hypercholesterolaemia from structure of LDL RT receptor module."; RL Nature 388:691-693(1997). RN [37] RP STRUCTURE BY NMR OF 20-104, AND DISULFIDE BONDS. RX PubMed=10933493; DOI=10.1110/ps.9.7.1282; RA Kurniawan N.D., Atkins A.R., Bieri S., Brown C.J., Brereton I.M., RA Kroon P.A., Smith R.; RT "NMR structure of a concatemer of the first and second ligand-binding RT modules of the human low-density lipoprotein receptor."; RL Protein Sci. 9:1282-1293(2000). RN [38] RP X-RAY CRYSTALLOGRAPHY (3.7 ANGSTROMS) OF 22-720, AND DISULFIDE BONDS. RX PubMed=12459547; DOI=10.1126/science.1078124; RA Rudenko G., Henry L., Henderson K., Ichtchenko K., Brown M.S., RA Goldstein J.L., Deisenhofer J.; RT "Structure of the LDL receptor extracellular domain at endosomal pH."; RL Science 298:2353-2358(2002). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 819-832 IN COMPLEX WITH LDLRAP1, RP INTERACTION WITH LDLRAP1, CHARACTERIZATION OF VARIANT FHCL1 CYS-828, RP MUTAGENESIS OF ILE-821 AND GLN-829, TOPOLOGY, AND MOTIF. RX PubMed=22509010; DOI=10.1073/pnas.1114128109; RA Dvir H., Shah M., Girardi E., Guo L., Farquhar M.G., Zajonc D.M.; RT "Atomic structure of the autosomal recessive hypercholesterolemia RT phosphotyrosine-binding domain in complex with the LDL-receptor tail."; RL Proc. Natl. Acad. Sci. U.S.A. 109:6916-6921(2012). RN [40] RP REVIEW ON FHCL1 VARIANTS. RX PubMed=9016531; DOI=10.1093/nar/25.1.172; RA Varret M., Rabes J.-P., Collod-Beroud G., Junien J., Boileau C., Beroud C.; RT "Software and database for the analysis of mutations in the human LDL RT receptor gene."; RL Nucleic Acids Res. 25:172-180(1997). RN [41] RP VARIANT FHCL1 CYS-828. RX PubMed=3955657; DOI=10.1016/0092-8674(86)90533-7; RA Davis C.G., Lehrman M.A., Russell D.W., Anderson R.G.W., Brown M.S., RA Goldstein J.L.; RT "The J.D. mutation in familial hypercholesterolemia: amino acid RT substitution in cytoplasmic domain impedes internalization of LDL RT receptors."; RL Cell 45:15-24(1986). RN [42] RP VARIANT FHCL1 47-ASP-GLY-48 DEL. RX PubMed=3263645; DOI=10.1073/pnas.85.21.7912; RA Leitersdorf E., Hobbs H.H., Fourie A.M., Jacobs M., RA van der Westhuyzen D.R., Coetzee G.A.; RT "Deletion in the first cysteine-rich repeat of low density lipoprotein RT receptor impairs its transport but not lipoprotein binding in fibroblasts RT from a subject with familial hypercholesterolemia."; RL Proc. Natl. Acad. Sci. U.S.A. 85:7912-7916(1988). RN [43] RP VARIANTS FHCL1 ASN-175; GLU-227 AND MET-429. RX PubMed=2569482; DOI=10.1172/jci114258; RA Leitersdorf E., van der Westhuyzen D.R., Coetzee G.A., Hobbs H.H.; RT "Two common low density lipoprotein receptor gene mutations cause familial RT hypercholesterolemia in Afrikaners."; RL J. Clin. Invest. 84:954-961(1989). RN [44] RP VARIANT FHCL1 LEU-685. RX PubMed=2726768; DOI=10.1073/pnas.86.11.4166; RA Soutar A.K., Knight B.L., Patel D.D.; RT "Identification of a point mutation in growth factor repeat C of the low RT density lipoprotein-receptor gene in a patient with homozygous familial RT hypercholesterolemia that affects ligand binding and intracellular movement RT of receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 86:4166-4170(1989). RN [45] RP VARIANTS FHCL1 GLY-87; LYS-228 AND TYR-667. RX PubMed=2318961; DOI=10.1172/jci114531; RA Leitersdorf E., Tobin E.J., Davignon J., Hobbs H.H.; RT "Common low-density lipoprotein receptor mutations in the French Canadian RT population."; RL J. Clin. Invest. 85:1014-1023(1990). RN [46] RP VARIANT FHCL1 GLY-218 DEL. RX PubMed=1867200; RA Meiner V., Landsberger D., Berkman N., Reshef A., Segal P., Seftel H.C., RA van der Westhuyzen D.R., Jeenah M.S., Coetzee G.A., Leitersdorf E.; RT "A common Lithuanian mutation causing familial hypercholesterolemia in RT Ashkenazi Jews."; RL Am. J. Hum. Genet. 49:443-449(1991). RN [47] RP VARIANT FHCL1 HIS-433. RX PubMed=1446662; DOI=10.1111/j.1432-1033.1992.tb17383.x; RA Miyake Y., Tajima S., Funahashi T., Yamamura T., Yamamoto A.; RT "A point mutation of low-density-lipoprotein receptor causing rapid RT degradation of the receptor."; RL Eur. J. Biochem. 210:1-7(1992). RN [48] RP VARIANTS FHCL1 TYR-52; ARG-109; GLY-155; ARG-173; PHE-197; TYR-197; RP ASN-224; GLY-224; PRO-226; LYS-240; PHE-248; GLY-256; GLU-266; TYR-270; RP ARG-286; ASN-304; GLU-304; TYR-318; SER-335; GLU-342; SER-343; TYR-352; RP VAL-354; GLY-354; LYS-357; ARG-364; ARG-379; ASN-441; MET-441; CYS-443; RP ARG-478; ARG-485; VAL-565; SER-599; PRO-682; PHE-792 AND ILE-827. RX PubMed=1301956; DOI=10.1002/humu.1380010602; RA Hobbs H.H., Brown M.S., Goldstein J.L.; RT "Molecular genetics of the LDL receptor gene in familial RT hypercholesterolemia."; RL Hum. Mutat. 1:445-466(1992). RN [49] RP VARIANT FHCL1 LEU-685. RX PubMed=1464748; RA Rubinsztein D.C., Coetzee G.A., Marais A.D., Leitersdorf E., Seftel H.C., RA van der Westhuyzen D.R.; RT "Identification and properties of the proline664-leucine mutant LDL RT receptor in South Africans of Indian origin."; RL J. Lipid Res. 33:1647-1655(1992). RN [50] RP VARIANTS FHCL1 TYR-90 AND LYS-140. RX PubMed=8347689; DOI=10.1016/0925-4439(93)90156-u; RA Rubinsztein D.C., Jialal I., Leitersdorf E., Coetzee G.A., RA van der Westhuyzen D.R.; RT "Identification of two new LDL-receptor mutations causing homozygous RT familial hypercholesterolemia in a South African of Indian origin."; RL Biochim. Biophys. Acta 1182:75-82(1993). RN [51] RP VARIANT FHCL1 HIS-168. RX PubMed=8462973; DOI=10.1007/bf00222714; RA Leitersdorf E., Reshef A., Meiner V., Dann E.J., Beigel Y., RA van Roggen F.G., van der Westhuyzen D.R., Coetzee G.A.; RT "A missense mutation in the low density lipoprotein receptor gene causes RT familial hypercholesterolemia in Sephardic Jews."; RL Hum. Genet. 91:141-147(1993). RN [52] RP VARIANT FHCL1 PHE-318. RX PubMed=8168830; DOI=10.1007/bf00202819; RA Lelli N., Garuti R., Pedrazzi P., Ghisellini M., Simone M.L., Tiozzo R., RA Cattin L., Valenti M., Rolleri M., Bertolini S., Stefanutti C., RA Calandra S.; RT "A new missense mutation (Cys297-->Phe) of the low density lipoprotein RT receptor in Italian patients with familial hypercholesterolemia RT (FHTrieste)."; RL Hum. Genet. 93:538-540(1994). RN [53] RP VARIANTS FHCL1 HIS-401 AND ASP-844. RX PubMed=7573037; RA Koivisto U.-M., Viikari J.S., Kontula K.; RT "Molecular characterization of minor gene rearrangements in Finnish RT patients with heterozygous familial hypercholesterolemia: identification of RT two common missense mutations (Gly823-->Asp and Leu380-->His) and eight RT rare mutations of the LDL receptor gene."; RL Am. J. Hum. Genet. 57:789-797(1995). RN [54] RP VARIANTS FHCL1 LYS-140; SER-338 AND LEU-685. RX PubMed=7583548; DOI=10.1161/01.atv.15.10.1713; RA Maruyama T., Miyake Y., Tajima S., Harada-Shiba M., Yamamura T., RA Tsushima M., Kishino B., Horiguchi Y., Funahashi T., Matsuzawa Y., RA Yamamoto A.; RT "Common mutations in the low-density-lipoprotein-receptor gene causing RT familial hypercholesterolemia in the Japanese population."; RL Arterioscler. Thromb. Vasc. Biol. 15:1713-1718(1995). RN [55] RP VARIANT FHCL1 FRENCH HIS-564. RX PubMed=7550239; DOI=10.1002/humu.1380060117; RA Tricot-Guerber F., Saint-Jore B., Valenti K., Foulon T., Bost M., RA Hadjian A.J.; RT "Identification of a mutation, N543H, in exon 11 of the low-density RT lipoprotein receptor gene in a French family with familial RT hypercholesterolemia."; RL Hum. Mutat. 6:87-88(1995). RN [56] RP VARIANTS FHCL1 LYS-277; THR-423 AND ASN-579. RX PubMed=7635461; DOI=10.1007/bf00207370; RA Ekstroem U., Abrahamson M., Sveger T., Lombardi P., Nilsson-Ehle P.; RT "An efficient screening procedure detecting six novel mutations in the LDL RT receptor gene in Swedish children with hypercholesterolemia."; RL Hum. Genet. 96:147-150(1995). RN [57] RP VARIANT FHCL1 NORWEGIAN ASN-487 DEL. RX PubMed=7635482; DOI=10.1007/bf00207391; RA Leren T.P., Solberg K., Rodningen O.K., Tonstad S., Ose L.; RT "Two novel point mutations in the EGF precursor homology domain of the LDL RT receptor gene causing familial hypercholesterolemia."; RL Hum. Genet. 96:241-242(1995). RN [58] RP VARIANTS FHCL1 COLOGNE GLY-221; TYR-221 AND VAL-224. RX PubMed=7649546; DOI=10.1007/bf00210411; RA Geisel J., Holzem G., Oette K.; RT "Screening for mutations in exon 4 of the LDL receptor gene in a German RT population with severe hypercholesterolemia."; RL Hum. Genet. 96:301-304(1995). RN [59] RP VARIANTS FHCL1 LA HABANA LYS-277; MET-429 AND MET-797. RX PubMed=7649549; DOI=10.1007/bf00210415; RA Pereira E., Ferreira R., Hermelin B., Thomas G., Bernard C., Bertrand V., RA Nassiff H., Mendez del Castillo D., Bereziat G., Benlian P.; RT "Recurrent and novel LDL receptor gene mutations causing heterozygous RT familial hypercholesterolemia in La Habana."; RL Hum. Genet. 96:319-322(1995). RN [60] RP VARIANTS FHCL1 TYR-168 AND ARG-366. RX PubMed=8740918; DOI=10.1111/j.1399-0004.1996.tb04333.x; RA Gundersen K.E., Solberg K., Rodningen O.K., Tonstad S., Ose L., Berg K., RA Leren T.P.; RT "Two novel missense mutations in the LDL receptor gene causing familial RT hypercholesterolemia."; RL Clin. Genet. 49:85-87(1996). RN [61] RP VARIANT FHCL1 GLY-231. RX PubMed=8664907; RX DOI=10.1002/(sici)1098-1004(1996)7:1<70::aid-humu12>3.0.co;2-p; RA Sundvold H., Solberg K., Tonstad S., Rodningen O.K., Ose L., Berg K., RA Leren T.P.; RT "A common missense mutation (C210G) in the LDL receptor gene among RT Norwegian familial hypercholesterolemia subjects."; RL Hum. Mutat. 7:70-71(1996). RN [62] RP VARIANTS FHCL1 ARG-197; TYR-248; ALA-301; TRP-302 AND PRO-350. RX PubMed=9026534; RA Webb J.C., Sun X.-M., McCarthy S.N., Neuwirth C., Thompson G.R., Knigh B., RA Soutar A.K.; RT "Characterization of mutations in the low density lipoprotein (LDL)- RT receptor gene in patients with homozygous familial hypercholesterolemia, RT and frequency of these mutations in FH patients in the United Kingdom."; RL J. Lipid Res. 37:368-381(1996). RN [63] RP VARIANT FHCL1 LEU-685. RX PubMed=9254862; DOI=10.1007/s004390050503; RA Peeters A.V., van Gaal L.F., du Plessis L., Lombardi M.P.R., Havekes L.M., RA Kotze M.J.; RT "Mutational and genetic origin of LDL receptor gene mutations detected in RT both Belgian and Dutch familial hypercholesterolemics."; RL Hum. Genet. 100:266-270(1997). RN [64] RP VARIANTS FHCL1 HIS-564 AND 799-LEU--PHE-801 DEL. RX PubMed=9143924; RX DOI=10.1002/(sici)1098-1004(1997)9:5<437::aid-humu10>3.0.co;2-3; RA Jensen H.K., Jensen T.G., Faergeman O., Jensen L.G., Andresen B.S., RA Corydon M.J., Andreasen P.H., Hansen P.S., Heath F., Bolund L., RA Gregersen N.; RT "Two mutations in the same low-density lipoprotein receptor allele act in RT synergy to reduce receptor function in heterozygous familial RT hypercholesterolemia."; RL Hum. Mutat. 9:437-444(1997). RN [65] RP VARIANTS FHCL1 TRP-27; CYS-78; GLY-87; TYR-89; ASN-90; GLY-90; LYS-101; RP TYR-160; ASN-168; LEU-177; GLY-221; GLU-227; ARG-286; TYR-313; TYR-327; RP ASN-342; PRO-350; ASP-399; TRP-416; HIS-482; ARG-483; SER-526; ASP-549; RP CYS-633; LEU-649 AND ILE-726. RX PubMed=9259195; RX DOI=10.1002/(sici)1098-1004(1997)10:2<116::aid-humu4>3.0.co;2-i; RA Day I.N.M., Whittall R.A., O'Dell S.D., Haddad L., Bolla M.K., Gudnason V., RA Humphries S.E.; RT "Spectrum of LDL receptor gene mutations in heterozygous familial RT hypercholesterolemia."; RL Hum. Mutat. 10:116-127(1997). RN [66] RP VARIANTS FHCL1 PRO-56; TYR-175; TYR-356; VAL-401 AND TRP-416. RX PubMed=9104431; DOI=10.1046/j.1365-2796.1997.78119000.x; RA Leren T.P., Tonstad S., Gundersen K.E., Bakken K.S., Rodningen O.K., RA Sundvold H., Ose L., Berg K.; RT "Molecular genetics of familial hypercholesterolaemia in Norway."; RL J. Intern. Med. 241:185-194(1997). RN [67] RP VARIANTS FHCL1 LEU-177; GLY-218 DEL; SER-564 AND GLU-592. RX PubMed=9654205; DOI=10.1007/s004390050740; RA Gorski B., Kubalska J., Naruszewicz M., Lubinski J.; RT "LDL-R and Apo-B-100 gene mutations in Polish familial RT hypercholesterolemias."; RL Hum. Genet. 102:562-565(1998). RN [68] RP VARIANTS FHCL1 TRP-173 AND ARG-368. RX PubMed=9452094; DOI=10.1002/humu.1380110173; RA Couture P., Vohl M.-C., Gagne C., Gaudet D., Torres A.L., Lupien P.J., RA Despres J.-P., Labrie F., Simard J., Moorjani S.; RT "Identification of three mutations in the low-density lipoprotein receptor RT gene causing familial hypercholesterolemia among French Canadians."; RL Hum. Mutat. Suppl. 1:S226-S231(1998). RN [69] RP VARIANTS FHCL1 GLN-416 AND MET-429. RX PubMed=9452095; DOI=10.1002/humu.1380110174; RA Thiart R., Loubser O., de Villiers J.N.P., Marx M.P., Zaire R., Raal F.J., RA Kotze M.J.; RT "Two novel and two known low-density lipoprotein receptor gene mutations in RT German patients with familial hypercholesterolemia."; RL Hum. Mutat. Suppl. 1:S232-S233(1998). RN [70] RP VARIANTS FHCL1 TYR-329; ARG-414 AND MET-429. RX PubMed=9452118; DOI=10.1002/humu.1380110197; RA Mak Y.T., Zhang J., Chan Y.S., Mak T.W.L., Tomlinson B., Masarei J.R.L., RA Pang C.P.; RT "Possible common mutations in the low density lipoprotein receptor gene in RT Chinese."; RL Hum. Mutat. Suppl. 1:S310-S313(1998). RN [71] RP VARIANTS FHCL1 GLU-92; GLY-95; ARG-116; LEU-177; GLY-221; TYR-221; LYS-277; RP TYR-302; LYS-434; TYR-667 AND GLU-700. RX PubMed=10206683; RA Cenarro A., Jensen H.K., Casao E., Civeira F., Gonzalez-Bonillo J., RA Rodriguez-Rey J.C., Gregersen N., Pocovi M.; RT "Identification of recurrent and novel mutations in the LDL receptor gene RT in Spanish patients with familial hypercholesterolemia."; RL Hum. Mutat. 11:413-413(1998). RN [72] RP VARIANT FHCL1 CHIETI-3 GLU-228 DELINS CYS-LYS. RX PubMed=10660340; RA Motti C., Bertolini S., Rampa P., Trovatello G., Liberatoscioli L., RA Calandra S., Federici G., Cortese C.; RT "Two novel mutations consisting in minor gene rearrangements in the human RT low density lipoprotein receptor gene in Italian patients affected by RT familial hypercholesterolemia."; RL Hum. Mutat. 12:290-290(1998). RN [73] RP VARIANT FHCL1 TYR-276. RA Vergopoulos A., Bajari T., Jouma M., Aydin A., Boehring S., Luft F.C., RA Schuster H.; RT "A novel single amino acid substitution in exon 6 of the low-density RT lipoprotein receptor gene in a Syrian family."; RL Hum. Mutat. 12:365-365(1998). RN [74] RP VARIANTS FHCL1 TYR-379 AND SER-608. RX PubMed=9852677; DOI=10.1007/s100380050083; RA Hirayama T., Yamaki E., Hata A., Tsuji M., Hashimoto K., Yamamoto M., RA Emi M.; RT "Five familial hypercholesterolemic kindreds in Japan with novel mutations RT of the LDL receptor gene."; RL J. Hum. Genet. 43:250-254(1998). RN [75] RP VARIANT FHCL1 GLASCO TYR-184. RX PubMed=9678702; DOI=10.1136/jmg.35.7.573; RA Lee W.K., Haddad L., Macleod M.J., Dorrance A.M., Wilson D.J., Gaffney D., RA Dominiczak M.H., Packard C.J., Day I.N., Humphries S.E., Dominiczak A.F.; RT "Identification of a common low density lipoprotein receptor mutation RT (C163Y) in the west of Scotland."; RL J. Med. Genet. 35:573-578(1998). RN [76] RP VARIANTS FHCL1 GLY-87; LYS-140; ASN-172; ARG-243; LEU-306; PRO-404; RP HIS-564; SER-577; ASN-579; ILE-726 AND LYS-825. RX PubMed=10532689; DOI=10.1016/s0021-9150(99)00158-6; RA Jensen H.K., Jensen L.G., Meinertz H., Hansen P.S., Gregersen N., RA Faergeman O.; RT "Spectrum of LDL receptor gene mutations in Denmark: implications for RT molecular diagnostic strategy in heterozygous familial RT hypercholesterolemia."; RL Atherosclerosis 146:337-344(1999). RN [77] RP VARIANT FHCL1 PHE-261. RX PubMed=10422803; DOI=10.1034/j.1399-0004.1999.550506.x; RA Ekstroem U., Abrahamson M., Floren C.-H., Tollig H., Wettrell G., RA Nilsson G., Sun X.-M., Soutar A.K., Nilsson-Ehle P.; RT "An individual with a healthy phenotype in spite of a pathogenic LDL RT receptor mutation (C240F)."; RL Clin. Genet. 55:332-339(1999). RN [78] RP VARIANTS FHCL1 SER-50; ASN-221; LYS-288; VAL-432 AND HIS-564. RX PubMed=10090484; RX DOI=10.1002/(sici)1098-1004(1999)13:3<257::aid-humu15>3.0.co;2-a; RA Ebhardt M., Schmidt H., Doerk T., Tietge U., Haas R., Manns M.-P., RA Schmidtke J., Stuhrmann M.; RT "Mutation analysis in 46 German families with familial RT hypercholesterolemia: identification of 8 new mutations."; RL Hum. Mutat. 13:257-257(1999). RN [79] RP VARIANTS FHCL1 SER-338; LEU-403; THR-431; VAL-568 AND LYS-714. RX PubMed=10447263; RA Hattori H., Nagano M., Iwata F., Homma Y., Egashira T., Okada T.; RT "Identification of recurrent and novel mutations in the LDL receptor gene RT in Japanese familial hypercholesterolemia."; RL Hum. Mutat. 14:87-87(1999). RN [80] RP VARIANTS ARG-2; ILE-468 AND GLN-814. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [81] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [82] RP VARIANTS FHCL1 PHE-134; TRP-134; TYR-222; PRO-254; ARG-276; ARG-318; RP THR-370; GLY-415 AND TYR-579. RX PubMed=10978268; DOI=10.1161/01.atv.20.9.e41; RA Bertolini S., Cantafora A., Averna M., Cortese C., Motti C., Martini S., RA Pes G., Postiglione A., Stefanutti C., Blotta I., Pisciotta L., Rolleri M., RA Langheim S., Ghisellini M., Rabbone I., Calandra S.; RT "Clinical expression of familial hypercholesterolemia in clusters of RT mutations of the LDL receptor gene that cause a receptor-defective or RT receptor-negative phenotype."; RL Arterioscler. Thromb. Vasc. Biol. 20:E41-E52(2000). RN [83] RP VARIANT FHCL1 THR-451. RX PubMed=10980548; RX DOI=10.1002/1098-1004(200009)16:3<277::aid-humu24>3.0.co;2-y; RA Miltiadous G., Elisaf M., Xenophontos S., Manoli P., Cariolou M.A.; RT "Segregation of a novel LDLR gene mutation (I430T) with familial RT hypercholesterolaemia in a Greek pedigree."; RL Hum. Mutat. 16:277-277(2000). RN [84] RP VARIANTS FHCL1 47-ASP-GLY-48 DEL AND TRP-253, AND VARIANTS HIS-172; RP GLN-406; LYS-408; LEU-699 AND GLN-814. RX PubMed=10882754; DOI=10.1136/jmg.37.7.514; RA Thiart R., Scholtz C.L., Vergotine J., Hoogendijk C.F., de Villiers J.N.P., RA Nissen H., Brusgaard K., Gaffney D., Hoffs M.S., Vermaak W.J.H., RA Kotze M.J.; RT "Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in RT Africans with familial hypercholesterolaemia."; RL J. Med. Genet. 37:514-519(2000). RN [85] RP VARIANT FHCL1 SER-46. RX PubMed=11298688; DOI=10.1034/j.1399-0004.2001.590414.x; RA Takahashi M., Ikeda U., Takahashi S., Hattori H., Iwasaki T., Ishihara M., RA Egashira T., Honma S., Asano Y., Shimada K.A.; RT "A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in RT a patient with homozygous familial hypercholesterolemia."; RL Clin. Genet. 59:290-292(2001). RN [86] RP INVOLVEMENT IN FHCL1, VARIANTS FHCL1 ARG-143; TYR-148; TRP-184; CYS-574; RP ASP-639 AND ASP-806, AND VARIANTS TRP-257 AND ILE-742. RX PubMed=11462246; DOI=10.1002/humu.1171; RA Nauck M.S., Koester W., Doerfer K., Eckes J., Scharnagl H., Gierens H., RA Nissen H., Nauck M.A., Wieland H., Maerz W.; RT "Identification of recurrent and novel mutations in the LDL receptor gene RT in German patients with familial hypercholesterolemia."; RL Hum. Mutat. 18:165-166(2001). RN [87] RP VARIANTS FHCL1 TYR-89; LYS-101; GLY-218 DEL; GLY-221; ASN-221; TYR-358; RP PRO-479; HIS-482; ARG-677 AND LEU-685, AND FUNCTION. RX PubMed=17142622; DOI=10.1136/jmg.2006.038356; RG Simon Broome familial hyperlipidemia register group and scientific steering committee; RA Humphries S.E., Whittall R.A., Hubbart C.S., Maplebeck S., Cooper J.A., RA Soutar A.K., Naoumova R., Thompson G.R., Seed M., Durrington P.N., RA Miller J.P., Betteridge D.J.B., Neil H.A.W.; RT "Genetic causes of familial hypercholesterolaemia in patients in the UK: RT relation to plasma lipid levels and coronary heart disease risk."; RL J. Med. Genet. 43:943-949(2006). RN [88] RP VARIANTS FHCL1 THR-50; LEU-211; GLY-221; GLU-266; LYS-277; ARG-286; RP ARG-314; ARG-352; LYS-408; THR-431; HIS-442; MET-523; GLY-577; THR-585 AND RP LEU-685. RX PubMed=17347910; DOI=10.1007/s10545-007-0563-5; RA Widhalm K., Dirisamer A., Lindemayr A., Kostner G.; RT "Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 RT defect by means of DNA analysis of LDL-receptor gene mutations."; RL J. Inherit. Metab. Dis. 30:239-247(2007). RN [89] RP VARIANTS FHCL1 TYR-155; GLY-300; GLY-301; TRP-416 AND ASN-454. RX PubMed=19318025; DOI=10.1016/j.clinbiochem.2009.01.017; RA Alonso R., Defesche J.C., Tejedor D., Castillo S., Stef M., Mata N., RA Gomez-Enterria P., Martinez-Faedo C., Forga L., Mata P.; RT "Genetic diagnosis of familial hypercholesterolemia using a DNA-array based RT platform."; RL Clin. Biochem. 42:899-903(2009). RN [90] RP VARIANTS FHCL1 PRO-254; TYR-356; TYR-358; THR-451 AND SER-826. RX PubMed=19319977; DOI=10.1002/humu.21002; RA Abifadel M., Rabes J.-P., Jambart S., Halaby G., Gannage-Yared M.-H., RA Sarkis A., Beaino G., Varret M., Salem N., Corbani S., Aydenian H., RA Junien C., Munnich A., Boileau C.; RT "The molecular basis of familial hypercholesterolemia in Lebanon: spectrum RT of LDLR mutations and role of PCSK9 as a modifier gene."; RL Hum. Mutat. 30:E682-E691(2009). RN [91] RP VARIANTS FHCL1 HIS-139; LYS-201; SER-255; ASN-304 AND GLY-471. RX PubMed=21418584; DOI=10.1186/1471-2350-12-40; RA Al-Khateeb A., Zahri M.K., Mohamed M.S., Sasongko T.H., Ibrahim S., RA Yusof Z., Zilfalil B.A.; RT "Analysis of sequence variations in low-density lipoprotein receptor gene RT among Malaysian patients with familial hypercholesterolemia."; RL BMC Med. Genet. 12:40-40(2011). RN [92] RP VARIANT FHCL1 PHE-329. RX PubMed=22160468; DOI=10.1007/s11033-011-1314-0; RA Walus-Miarka M., Sanak M., Idzior-Walus B., Miarka P., Witek P., RA Malecki M.T., Czarnecka D.; RT "A novel mutation (Cys308Phe) of the LDL receptor gene in families from the RT South-Eastern part of Poland."; RL Mol. Biol. Rep. 39:5181-5186(2012). RN [93] RP VARIANTS FHCL1 TYR-160; ALA-168; LEU-177; TYR-184; GLY-221; GLN-228; RP LYS-228; TRP-276; TYR-285; GLY-301; PHE-318; CYS-326; SER-343; TYR-368; RP ASP-373; TRP-406; MET-429; ASN-492; ASP-549; HIS-564; HIS-574; TRP-595; RP HIS-601; LEU-685; LEU-699; MET-797 AND GLN-814. RX PubMed=24529145; DOI=10.1016/j.atherosclerosis.2013.12.028; RA Santos P.C., Morgan A.C., Jannes C.E., Turolla L., Krieger J.E., RA Santos R.D., Pereira A.C.; RT "Presence and type of low density lipoprotein receptor (LDLR) mutation RT influences the lipid profile and response to lipid-lowering therapy in RT Brazilian patients with heterozygous familial hypercholesterolemia."; RL Atherosclerosis 233:206-210(2014). RN [94] RP CHARACTERIZATION OF VARIANTS FHCL1 ARG-116; ASN-168; ASN-172; GLY-300 AND RP GLY-301, AND CHARACTERIZATION OF VARIANT TRP-257. RX PubMed=25545329; DOI=10.1016/j.atherosclerosis.2014.12.026; RA Etxebarria A., Benito-Vicente A., Stef M., Ostolaza H., Palacios L., RA Martin C.; RT "Activity-associated effect of LDL receptor missense variants located in RT the cysteine-rich repeats."; RL Atherosclerosis 238:304-312(2015). RN [95] RP CHARACTERIZATION OF VARIANTS FHCL1 TYR-155; TRP-416; ASN-454; GLY-577 AND RP LYS-825. RX PubMed=25378237; DOI=10.1002/humu.22721; RA Etxebarria A., Benito-Vicente A., Palacios L., Stef M., Cenarro A., RA Civeira F., Ostolaza H., Martin C.; RT "Functional characterization and classification of frequent low-density RT lipoprotein receptor variants."; RL Hum. Mutat. 36:129-141(2015). CC -!- FUNCTION: Binds low density lipoprotein /LDL, the major cholesterol- CC carrying lipoprotein of plasma, and transports it into cells by CC endocytosis. In order to be internalized, the receptor-ligand complexes CC must first cluster into clathrin-coated pits. Forms a ternary complex CC with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL CC internalization (PubMed:30443021). {ECO:0000269|PubMed:3005267, CC ECO:0000269|PubMed:30443021, ECO:0000269|PubMed:6091915}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C CC virus in hepatocytes, but not through a direct interaction with viral CC proteins. {ECO:0000269|PubMed:10535997, ECO:0000269|PubMed:12615904}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Vesicular CC stomatitis virus. {ECO:0000269|PubMed:23589850}. CC -!- FUNCTION: (Microbial infection) In case of HIV-1 infection, may CC function as a receptor for extracellular Tat in neurons, mediating its CC internalization in uninfected cells. {ECO:0000269|PubMed:11100124}. CC -!- SUBUNIT: Interacts (via NPXY motif) with DAB2 (via PID domain); the CC interaction is impaired by tyrosine phosphorylation of the NPXY motif CC (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID CC domain) (PubMed:12221107, PubMed:22509010). Interacts with ARRB1 CC (PubMed:12944399). Interacts with SNX17 (PubMed:14739284). Interacts CC with the full-length immature form of PCSK9 (via C-terminus) CC (PubMed:17461796, PubMed:21149300). Interacts with PGRMC1 and TMEM97; CC the interaction increases LDL internalization (PubMed:30443021). CC {ECO:0000250|UniProtKB:P35951, ECO:0000269|PubMed:12221107, CC ECO:0000269|PubMed:12944399, ECO:0000269|PubMed:14739284, CC ECO:0000269|PubMed:17461796, ECO:0000269|PubMed:21149300, CC ECO:0000269|PubMed:22509010, ECO:0000269|PubMed:30443021}. CC -!- SUBUNIT: (Microbial infection) Interacts with C.difficile toxin TcdA, CC suggesting that it may contribute to TcdA toxin entry into cells. CC {ECO:0000269|PubMed:31160825}. CC -!- SUBUNIT: (Microbial infection) Interacts with vesicular stomatitis CC virus glycoprotein. {ECO:0000269|PubMed:23589850}. CC -!- SUBUNIT: (Microbial infection) May interact with HIV-1 Tat. CC {ECO:0000269|PubMed:11100124}. CC -!- INTERACTION: CC P01130; P04114: APOB; NbExp=4; IntAct=EBI-988319, EBI-3926040; CC P01130; P02649: APOE; NbExp=4; IntAct=EBI-988319, EBI-1222467; CC P01130; P02749: APOH; NbExp=3; IntAct=EBI-988319, EBI-2114682; CC P01130; P01130: LDLR; NbExp=3; IntAct=EBI-988319, EBI-988319; CC P01130; P30533: LRPAP1; NbExp=3; IntAct=EBI-988319, EBI-715927; CC P01130; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-988319, EBI-3923617; CC P01130; Q8NBP7: PCSK9; NbExp=10; IntAct=EBI-988319, EBI-7539251; CC P01130; Q8NBP7-1: PCSK9; NbExp=4; IntAct=EBI-988319, EBI-15656131; CC P01130; Q08117-2: TLE5; NbExp=3; IntAct=EBI-988319, EBI-11741437; CC P01130; D3ZAR1: Ldlrap1; Xeno; NbExp=3; IntAct=EBI-988319, EBI-9250714; CC P01130; P0DTC2: S; Xeno; NbExp=4; IntAct=EBI-988319, EBI-25474821; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17461796, CC ECO:0000269|PubMed:19520913}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P01131}. Membrane, clathrin-coated pit CC {ECO:0000303|PubMed:6091915}. Golgi apparatus CC {ECO:0000269|PubMed:17461796}. Early endosome CC {ECO:0000269|PubMed:17461796}. Late endosome CC {ECO:0000269|PubMed:17461796}. Lysosome {ECO:0000269|PubMed:17461796}. CC Note=Rapidly endocytosed upon ligand binding. Localized at cell CC membrane, probably in lipid rafts, in serum-starved conditions CC (PubMed:30443021). {ECO:0000269|PubMed:30443021, CC ECO:0000269|PubMed:3104336}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=P01130-1; Sequence=Displayed; CC Name=2; CC IsoId=P01130-2; Sequence=VSP_043053, VSP_043054; CC Name=3; CC IsoId=P01130-3; Sequence=VSP_055014, VSP_055015; CC Name=4; CC IsoId=P01130-4; Sequence=VSP_043595; CC Name=5; CC IsoId=P01130-5; Sequence=VSP_045525; CC Name=6; CC IsoId=P01130-6; Sequence=VSP_047413; CC -!- DOMAIN: The NPXY motif mediates the interaction with the clathrin CC adapter DAB2 and with LDLRAP1 which are involved in receptor CC internalization. A few residues outside the motif also play a role in CC the interaction. {ECO:0000269|PubMed:22509010}. CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:12754519, CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, CC ECO:0000269|PubMed:19520913, ECO:0000269|PubMed:3005267}. CC -!- PTM: Ubiquitinated by MYLIP leading to degradation. CC {ECO:0000269|PubMed:19520913}. CC -!- DISEASE: Hypercholesterolemia, familial, 1 (FHCL1) [MIM:143890]: A form CC of hypercholesterolemia, a disorder of lipoprotein metabolism CC characterized by elevated serum low-density lipoprotein (LDL) CC cholesterol levels, which result in excess deposition of cholesterol in CC tissues and leads to xanthelasma, xanthomas, accelerated CC atherosclerosis and increased risk of premature coronary heart disease. CC FHCL1 inheritance is autosomal dominant. {ECO:0000269|PubMed:10090484, CC ECO:0000269|PubMed:10206683, ECO:0000269|PubMed:10422803, CC ECO:0000269|PubMed:10447263, ECO:0000269|PubMed:10532689, CC ECO:0000269|PubMed:10660340, ECO:0000269|PubMed:10882754, CC ECO:0000269|PubMed:10978268, ECO:0000269|PubMed:10980548, CC ECO:0000269|PubMed:11298688, ECO:0000269|PubMed:11462246, CC ECO:0000269|PubMed:1301956, ECO:0000269|PubMed:1446662, CC ECO:0000269|PubMed:1464748, ECO:0000269|PubMed:17142622, CC ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:1867200, CC ECO:0000269|PubMed:19318025, ECO:0000269|PubMed:19319977, CC ECO:0000269|PubMed:21418584, ECO:0000269|PubMed:22160468, CC ECO:0000269|PubMed:22509010, ECO:0000269|PubMed:2318961, CC ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25378237, CC ECO:0000269|PubMed:25545329, ECO:0000269|PubMed:2569482, CC ECO:0000269|PubMed:2726768, ECO:0000269|PubMed:3263645, CC ECO:0000269|PubMed:3955657, ECO:0000269|PubMed:7550239, CC ECO:0000269|PubMed:7573037, ECO:0000269|PubMed:7583548, CC ECO:0000269|PubMed:7635461, ECO:0000269|PubMed:7635482, CC ECO:0000269|PubMed:7649546, ECO:0000269|PubMed:7649549, CC ECO:0000269|PubMed:8168830, ECO:0000269|PubMed:8347689, CC ECO:0000269|PubMed:8462973, ECO:0000269|PubMed:8664907, CC ECO:0000269|PubMed:8740918, ECO:0000269|PubMed:9026534, CC ECO:0000269|PubMed:9104431, ECO:0000269|PubMed:9143924, CC ECO:0000269|PubMed:9254862, ECO:0000269|PubMed:9259195, CC ECO:0000269|PubMed:9452094, ECO:0000269|PubMed:9452095, CC ECO:0000269|PubMed:9452118, ECO:0000269|PubMed:9654205, CC ECO:0000269|PubMed:9678702, ECO:0000269|PubMed:9852677, CC ECO:0000269|Ref.73}. Note=The disease is caused by variants affecting CC the gene represented in this entry. CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92646.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=LDLR; Note=LDLR mutation database; CC URL="https://www.ucl.ac.uk/ldlr/LOVDv.1.1.0/index/"; 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; L00352; AAA56833.1; -; Genomic_DNA. DR EMBL; L00336; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00337; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00338; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00339; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00340; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00341; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00343; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00344; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00345; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00346; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00347; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00348; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00349; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00350; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L00351; AAA56833.1; JOINED; Genomic_DNA. DR EMBL; L29401; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY114155; AAM56036.1; -; mRNA. DR EMBL; AK295612; BAG58495.1; -; mRNA. DR EMBL; AK296312; BAG59010.1; -; mRNA. DR EMBL; AK299038; BAG61112.1; -; mRNA. DR EMBL; AK300313; BAG62065.1; -; mRNA. DR EMBL; BT007361; AAP36025.1; -; mRNA. DR EMBL; AY324609; AAP72971.1; -; Genomic_DNA. DR EMBL; AB209409; BAD92646.1; ALT_INIT; mRNA. DR EMBL; FJ525879; ACN81317.1; -; Genomic_DNA. DR EMBL; AC011485; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471106; EAW84169.1; -; Genomic_DNA. DR EMBL; BC014514; AAH14514.1; -; mRNA. DR CCDS; CCDS12254.1; -. [P01130-1] DR CCDS; CCDS56083.1; -. [P01130-2] DR CCDS; CCDS56084.1; -. [P01130-3] DR CCDS; CCDS56085.1; -. [P01130-4] DR CCDS; CCDS58651.1; -. [P01130-5] DR PIR; A01383; QRHULD. DR RefSeq; NP_000518.1; NM_000527.4. [P01130-1] DR RefSeq; NP_001182727.1; NM_001195798.1. [P01130-5] DR RefSeq; NP_001182728.1; NM_001195799.1. [P01130-4] DR RefSeq; NP_001182729.1; NM_001195800.1. [P01130-3] DR RefSeq; NP_001182732.1; NM_001195803.1. [P01130-2] DR PDB; 1AJJ; X-ray; 1.70 A; A=196-232. DR PDB; 1D2J; NMR; -; A=233-272. DR PDB; 1F5Y; NMR; -; A=22-104. DR PDB; 1F8Z; NMR; -; A=234-272. DR PDB; 1HJ7; NMR; -; A=314-393. DR PDB; 1HZ8; NMR; -; A=314-395. DR PDB; 1I0U; NMR; -; A=314-395. DR PDB; 1IJQ; X-ray; 1.50 A; A/B=398-713. DR PDB; 1LDL; NMR; -; A=20-67. DR PDB; 1LDR; NMR; -; A=64-104. DR PDB; 1N7D; X-ray; 3.70 A; A=22-720. DR PDB; 1XFE; NMR; -; A=272-353. DR PDB; 2FCW; X-ray; 1.26 A; B=107-186. DR PDB; 2KRI; NMR; -; B=147-186. DR PDB; 2LGP; NMR; -; A=144-235. DR PDB; 2M7P; NMR; -; A=82-104. DR PDB; 2MG9; NMR; -; A=314-339. DR PDB; 2W2M; X-ray; 2.40 A; E=314-393. DR PDB; 2W2N; X-ray; 2.30 A; E=314-393. DR PDB; 2W2O; X-ray; 2.62 A; E=314-393. DR PDB; 2W2P; X-ray; 2.62 A; E=314-393. DR PDB; 2W2Q; X-ray; 2.33 A; E=314-393. DR PDB; 3BPS; X-ray; 2.41 A; E=314-393. DR PDB; 3GCW; X-ray; 2.70 A; E=314-393. DR PDB; 3GCX; X-ray; 2.70 A; E=314-393. DR PDB; 3M0C; X-ray; 7.01 A; C=4-788. DR PDB; 3P5B; X-ray; 3.30 A; L=316-715. DR PDB; 3P5C; X-ray; 4.20 A; L=276-715. DR PDB; 3SO6; X-ray; 1.37 A; Q=819-832. DR PDB; 4NE9; X-ray; 2.60 A; D=314-339. DR PDB; 5OY9; X-ray; 3.60 A; D=108-144. DR PDB; 5OYL; X-ray; 2.25 A; D=65-106. DR PDBsum; 1AJJ; -. DR PDBsum; 1D2J; -. DR PDBsum; 1F5Y; -. DR PDBsum; 1F8Z; -. DR PDBsum; 1HJ7; -. DR PDBsum; 1HZ8; -. DR PDBsum; 1I0U; -. DR PDBsum; 1IJQ; -. DR PDBsum; 1LDL; -. DR PDBsum; 1LDR; -. DR PDBsum; 1N7D; -. DR PDBsum; 1XFE; -. DR PDBsum; 2FCW; -. DR PDBsum; 2KRI; -. DR PDBsum; 2LGP; -. DR PDBsum; 2M7P; -. DR PDBsum; 2MG9; -. DR PDBsum; 2W2M; -. DR PDBsum; 2W2N; -. DR PDBsum; 2W2O; -. DR PDBsum; 2W2P; -. DR PDBsum; 2W2Q; -. DR PDBsum; 3BPS; -. DR PDBsum; 3GCW; -. DR PDBsum; 3GCX; -. DR PDBsum; 3M0C; -. DR PDBsum; 3P5B; -. DR PDBsum; 3P5C; -. DR PDBsum; 3SO6; -. DR PDBsum; 4NE9; -. DR PDBsum; 5OY9; -. DR PDBsum; 5OYL; -. DR AlphaFoldDB; P01130; -. DR BMRB; P01130; -. DR SMR; P01130; -. DR BioGRID; 110141; 459. DR ComplexPortal; CPX-128; LDLR-PCSK9 complex. DR DIP; DIP-29695N; -. DR ELM; P01130; -. DR IntAct; P01130; 49. DR MINT; P01130; -. DR STRING; 9606.ENSP00000454071; -. DR BindingDB; P01130; -. DR ChEMBL; CHEMBL3311; -. DR DrugBank; DB14003; alpha-Tocopherol acetate. DR DrugBank; DB00080; Daptomycin. DR DrugBank; DB00707; Porfimer sodium. DR DrugBank; DB11251; Tocopherol. DR DrugBank; DB09270; Ubidecarenone. DR TCDB; 9.B.87.1.42; the selenoprotein p receptor (selp-receptor) family. DR GlyConnect; 343; 10 N-Linked glycans (4 sites), 4 O-Linked glycans. DR GlyCosmos; P01130; 11 sites, 19 glycans. DR GlyGen; P01130; 23 sites, 9 N-linked glycans (4 sites), 10 O-linked glycans (17 sites). DR iPTMnet; P01130; -. DR PhosphoSitePlus; P01130; -. DR SwissPalm; P01130; -. DR BioMuta; LDLR; -. DR DMDM; 126073; -. DR EPD; P01130; -. DR jPOST; P01130; -. DR MassIVE; P01130; -. DR MaxQB; P01130; -. DR PaxDb; 9606-ENSP00000454071; -. DR PeptideAtlas; P01130; -. DR ProteomicsDB; 40062; -. DR ProteomicsDB; 40658; -. DR ProteomicsDB; 51326; -. [P01130-1] DR ProteomicsDB; 51327; -. [P01130-2] DR ProteomicsDB; 51328; -. [P01130-3] DR ProteomicsDB; 51329; -. [P01130-4] DR Pumba; P01130; -. DR Antibodypedia; 2424; 1073 antibodies from 43 providers. DR DNASU; 3949; -. DR Ensembl; ENST00000455727.6; ENSP00000397829.2; ENSG00000130164.15. [P01130-3] DR Ensembl; ENST00000535915.5; ENSP00000440520.1; ENSG00000130164.15. [P01130-4] DR Ensembl; ENST00000545707.5; ENSP00000437639.1; ENSG00000130164.15. [P01130-2] DR Ensembl; ENST00000558013.5; ENSP00000453346.1; ENSG00000130164.15. [P01130-5] DR Ensembl; ENST00000558518.6; ENSP00000454071.1; ENSG00000130164.15. [P01130-1] DR GeneID; 3949; -. DR KEGG; hsa:3949; -. DR MANE-Select; ENST00000558518.6; ENSP00000454071.1; NM_000527.5; NP_000518.1. DR UCSC; uc002mqk.5; human. [P01130-1] DR AGR; HGNC:6547; -. DR CTD; 3949; -. DR DisGeNET; 3949; -. DR GeneCards; LDLR; -. DR GeneReviews; LDLR; -. DR HGNC; HGNC:6547; LDLR. DR HPA; ENSG00000130164; Tissue enhanced (adrenal). DR MalaCards; LDLR; -. DR MIM; 143890; phenotype. DR MIM; 606945; gene. DR neXtProt; NX_P01130; -. DR OpenTargets; ENSG00000130164; -. DR Orphanet; 391665; Homozygous familial hypercholesterolemia. DR Orphanet; 406; NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia. DR PharmGKB; PA227; -. DR VEuPathDB; HostDB:ENSG00000130164; -. DR eggNOG; KOG1215; Eukaryota. DR GeneTree; ENSGT00940000161046; -. DR HOGENOM; CLU_008163_4_0_1; -. DR InParanoid; P01130; -. DR OMA; GSRQCNK; -. DR OrthoDB; 3918101at2759; -. DR PhylomeDB; P01130; -. DR TreeFam; TF351700; -. DR PathwayCommons; P01130; -. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8964026; Chylomicron clearance. DR Reactome; R-HSA-8964038; LDL clearance. DR Reactome; R-HSA-975634; Retinoid metabolism and transport. DR SignaLink; P01130; -. DR SIGNOR; P01130; -. DR BioGRID-ORCS; 3949; 65 hits in 1186 CRISPR screens. DR ChiTaRS; LDLR; human. DR EvolutionaryTrace; P01130; -. DR GeneWiki; LDL_receptor; -. DR GenomeRNAi; 3949; -. DR Pharos; P01130; Tchem. DR PRO; PR:P01130; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P01130; Protein. DR Bgee; ENSG00000130164; Expressed in adrenal tissue and 196 other cell types or tissues. DR ExpressionAtlas; P01130; baseline and differential. DR GO; GO:0045177; C:apical part of cell; ISS:BHF-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:BHF-UCL. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005905; C:clathrin-coated pit; IDA:BHF-UCL. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0034362; C:low-density lipoprotein particle; IEA:UniProtKB-KW. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:1990666; C:PCSK9-LDLR complex; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; ISS:ARUK-UCL. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0036477; C:somatodendritic compartment; IEA:Ensembl. DR GO; GO:0097443; C:sorting endosome; IEA:Ensembl. DR GO; GO:0001540; F:amyloid-beta binding; ISS:ARUK-UCL. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0032050; F:clathrin heavy chain binding; TAS:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0071813; F:lipoprotein particle binding; IBA:GO_Central. DR GO; GO:0030169; F:low-density lipoprotein particle binding; IMP:BHF-UCL. DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IDA:BHF-UCL. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; IDA:BHF-UCL. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL. DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; ISS:ARUK-UCL. DR GO; GO:0048844; P:artery morphogenesis; IEA:Ensembl. DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IMP:BHF-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL. DR GO; GO:0070508; P:cholesterol import; IMP:BHF-UCL. DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW. DR GO; GO:0030301; P:cholesterol transport; IMP:HGNC-UCL. DR GO; GO:0006897; P:endocytosis; TAS:ProtInc. DR GO; GO:0034384; P:high-density lipoprotein particle clearance; IEA:Ensembl. DR GO; GO:0030299; P:intestinal cholesterol absorption; IMP:HGNC-UCL. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. DR GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl. DR GO; GO:0007616; P:long-term memory; IGI:ARUK-UCL. DR GO; GO:0034383; P:low-density lipoprotein particle clearance; IMP:BHF-UCL. DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISS:ARUK-UCL. DR GO; GO:0061889; P:negative regulation of astrocyte activation; ISS:ARUK-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; IDA:ComplexPortal. DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:ARUK-UCL. DR GO; GO:0051248; P:negative regulation of protein metabolic process; ISS:ARUK-UCL. DR GO; GO:0001920; P:negative regulation of receptor recycling; IDA:ComplexPortal. DR GO; GO:0006909; P:phagocytosis; ISS:ARUK-UCL. DR GO; GO:0015914; P:phospholipid transport; ISS:BHF-UCL. DR GO; GO:0034381; P:plasma lipoprotein particle clearance; ISS:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl. DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; ISS:ARUK-UCL. DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISS:BHF-UCL. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:ARUK-UCL. DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IMP:BHF-UCL. DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IEA:Ensembl. DR GO; GO:0010899; P:regulation of phosphatidylcholine catabolic process; ISS:BHF-UCL. DR GO; GO:0051246; P:regulation of protein metabolic process; IGI:ARUK-UCL. DR GO; GO:0061771; P:response to caloric restriction; IGI:ARUK-UCL. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00112; LDLa; 7. DR DisProt; DP01396; -. DR Gene3D; 4.10.1220.10; EGF-type module; 1. DR Gene3D; 2.10.25.10; Laminin; 3. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 6. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1. DR IDEAL; IID00646; -. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR036055; LDL_receptor-like_sf. DR InterPro; IPR023415; LDLR_class-A_CS. DR InterPro; IPR000033; LDLR_classB_rpt. DR InterPro; IPR002172; LDrepeatLR_classA_rpt. DR PANTHER; PTHR24270:SF21; LOW-DENSITY LIPOPROTEIN RECEPTOR; 1. DR PANTHER; PTHR24270; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF14670; FXa_inhibition; 2. DR Pfam; PF00057; Ldl_recept_a; 7. DR Pfam; PF00058; Ldl_recept_b; 5. DR PRINTS; PR00261; LDLRECEPTOR. DR SMART; SM00181; EGF; 3. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00192; LDLa; 7. DR SMART; SM00135; LY; 5. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF57424; LDL receptor-like module; 7. DR SUPFAM; SSF63825; YWTD domain; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 2. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50026; EGF_3; 2. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS01209; LDLRA_1; 7. DR PROSITE; PS50068; LDLRA_2; 7. DR PROSITE; PS51120; LDLRB; 5. DR Genevisible; P01130; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cholesterol metabolism; KW Coated pit; Direct protein sequencing; Disease variant; Disulfide bond; KW EGF-like domain; Endocytosis; Endosome; Glycoprotein; Golgi apparatus; KW Host cell receptor for virus entry; Host-virus interaction; LDL; KW Lipid metabolism; Lipid transport; Lysosome; Membrane; Phosphoprotein; KW Receptor; Reference proteome; Repeat; Signal; Steroid metabolism; KW Sterol metabolism; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation. FT SIGNAL 1..21 FT /evidence="ECO:0000250|UniProtKB:P01131" FT CHAIN 22..860 FT /note="Low-density lipoprotein receptor" FT /id="PRO_0000017312" FT TOPO_DOM 22..788 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P01131" FT TRANSMEM 789..810 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 811..860 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:22509010" FT DOMAIN 25..65 FT /note="LDL-receptor class A 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 66..106 FT /note="LDL-receptor class A 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 107..145 FT /note="LDL-receptor class A 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 146..186 FT /note="LDL-receptor class A 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 195..233 FT /note="LDL-receptor class A 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 234..272 FT /note="LDL-receptor class A 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 274..313 FT /note="LDL-receptor class A 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 314..353 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 354..393 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 397..438 FT /note="LDL-receptor class B 1" FT REPEAT 439..485 FT /note="LDL-receptor class B 2" FT REPEAT 486..528 FT /note="LDL-receptor class B 3" FT REPEAT 529..572 FT /note="LDL-receptor class B 4" FT REPEAT 573..615 FT /note="LDL-receptor class B 5" FT REPEAT 616..658 FT /note="LDL-receptor class B 6" FT DOMAIN 663..712 FT /note="EGF-like 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REGION 721..768 FT /note="Clustered O-linked oligosaccharides" FT REGION 734..755 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 811..860 FT /note="Required for MYLIP-triggered down-regulation of FT LDLR" FT /evidence="ECO:0000269|PubMed:19520913" FT MOTIF 823..828 FT /note="NPXY motif" FT /evidence="ECO:0000269|PubMed:22509010" FT COMPBIAS 734..749 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 724 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P35952" FT CARBOHYD 97 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 156 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19520913" FT CARBOHYD 272 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19520913" FT CARBOHYD 515 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 657 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218" FT DISULFID 27..39 FT DISULFID 34..52 FT DISULFID 46..63 FT DISULFID 68..82 FT DISULFID 75..95 FT DISULFID 89..104 FT DISULFID 109..121 FT /evidence="ECO:0000250" FT DISULFID 116..134 FT DISULFID 128..143 FT DISULFID 148..160 FT DISULFID 155..173 FT DISULFID 167..184 FT DISULFID 197..209 FT DISULFID 204..222 FT DISULFID 216..231 FT DISULFID 236..248 FT DISULFID 243..261 FT DISULFID 255..270 FT DISULFID 276..289 FT DISULFID 284..302 FT DISULFID 296..313 FT DISULFID 318..329 FT DISULFID 325..338 FT DISULFID 340..352 FT DISULFID 358..368 FT DISULFID 364..377 FT DISULFID 379..392 FT DISULFID 667..681 FT DISULFID 677..696 FT DISULFID 698..711 FT VAR_SEQ 35..155 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047413" FT VAR_SEQ 64..105 FT /note="LSVTCKSGDFSCGGRVNRCIPQFWRCDGQVDCDNGSDEQGCP -> S (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043595" FT VAR_SEQ 105..272 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055014" FT VAR_SEQ 106..232 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043053" FT VAR_SEQ 273 FT /note="V -> L (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055015" FT VAR_SEQ 663..713 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043054" FT VAR_SEQ 850..851 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_045525" FT VARIANT 2 FT /note="G -> R (in dbSNP:rs5931)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_011862" FT VARIANT 27 FT /note="C -> W (in FHCL1; pathogenic; San Francisco; FT dbSNP:rs2228671)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005304" FT VARIANT 46 FT /note="C -> S (in FHCL1; dbSNP:rs121908041)" FT /evidence="ECO:0000269|PubMed:11298688" FT /id="VAR_013949" FT VARIANT 47..48 FT /note="Missing (in FHCL1; Cape Town-1; retards receptor FT transport from the endoplasmic reticulum to the cell FT surface)" FT /evidence="ECO:0000269|PubMed:10882754, FT ECO:0000269|PubMed:3263645" FT /id="VAR_005305" FT VARIANT 50 FT /note="A -> S (in FHCL1; dbSNP:rs137853960)" FT /evidence="ECO:0000269|PubMed:10090484" FT /id="VAR_007979" FT VARIANT 50 FT /note="A -> T (in FHCL1; uncertain significance; FT dbSNP:rs137853960)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072827" FT VARIANT 52 FT /note="C -> Y (in FHCL1; Paris-4; dbSNP:rs879254418)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005306" FT VARIANT 56 FT /note="S -> P (in FHCL1; dbSNP:rs878854026)" FT /evidence="ECO:0000269|PubMed:9104431" FT /id="VAR_007980" FT VARIANT 78 FT /note="R -> C (in FHCL1; uncertain significance; FT dbSNP:rs370860696)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005307" FT VARIANT 87 FT /note="W -> G (in FHCL1; pathogenic; French Canadian-4; FT dbSNP:rs121908025)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:2318961, ECO:0000269|PubMed:9259195" FT /id="VAR_005308" FT VARIANT 89 FT /note="C -> Y (in FHCL1; dbSNP:rs875989894)" FT /evidence="ECO:0000269|PubMed:17142622, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005309" FT VARIANT 90 FT /note="D -> G (in FHCL1; pathogenic; London-4; FT dbSNP:rs771019366)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005310" FT VARIANT 90 FT /note="D -> N (in FHCL1; pathogenic; dbSNP:rs749038326)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005311" FT VARIANT 90 FT /note="D -> Y (in FHCL1; likely pathogenic; Durban-1; FT dbSNP:rs749038326)" FT /evidence="ECO:0000269|PubMed:8347689" FT /id="VAR_005312" FT VARIANT 92 FT /note="Q -> E (in FHCL1; dbSNP:rs774467219)" FT /evidence="ECO:0000269|PubMed:10206683" FT /id="VAR_005313" FT VARIANT 95 FT /note="C -> G (in FHCL1; dbSNP:rs879254456)" FT /evidence="ECO:0000269|PubMed:10206683" FT /id="VAR_005314" FT VARIANT 101 FT /note="E -> K (in FHCL1; pathogenic; Lancashire; 6% of FT American English; dbSNP:rs144172724)" FT /evidence="ECO:0000269|PubMed:17142622, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005315" FT VARIANT 105 FT /note="P -> S (in dbSNP:rs13306510)" FT /id="VAR_059375" FT VARIANT 109 FT /note="C -> R (in FHCL1; uncertain significance; Munster-1; FT dbSNP:rs140807148)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005316" FT VARIANT 116 FT /note="C -> R (in FHCL1; does not affect receptor FT expression at the cell surface; results in reduced LDL FT binding; results in reduced LDL uptake and internalization; FT dbSNP:rs879254482)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:25545329" FT /id="VAR_005317" FT VARIANT 134 FT /note="C -> F (in FHCL1; dbSNP:rs879254514)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062371" FT VARIANT 134 FT /note="C -> W (in FHCL1; dbSNP:rs879254515)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062372" FT VARIANT 139 FT /note="D -> H (in FHCL1; dbSNP:rs879254517)" FT /evidence="ECO:0000269|PubMed:21418584" FT /id="VAR_065780" FT VARIANT 140 FT /note="E -> K (in FHCL1; pathogenic; FT Philippines/Durban-2/Japan; dbSNP:rs748944640)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:8347689" FT /id="VAR_005318" FT VARIANT 143 FT /note="C -> R (in FHCL1; dbSNP:rs875989901)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072828" FT VARIANT 148 FT /note="C -> Y (in FHCL1; dbSNP:rs879254526)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072829" FT VARIANT 155 FT /note="C -> G (in FHCL1; Germany; dbSNP:rs879254535)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005319" FT VARIANT 155 FT /note="C -> Y (in FHCL1; results in defective LDL binding; FT does not affect receptor expression at the cell surface; FT dbSNP:rs879254536)" FT /evidence="ECO:0000269|PubMed:19318025, FT ECO:0000269|PubMed:25378237" FT /id="VAR_072830" FT VARIANT 160 FT /note="C -> Y (in FHCL1; uncertain significance; FT dbSNP:rs879254541)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005320" FT VARIANT 168 FT /note="D -> A (in FHCL1; uncertain significance; FT dbSNP:rs879254549)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072831" FT VARIANT 168 FT /note="D -> H (in FHCL1; Sephardic/Safed; 10% of the FT Sephardic Jews; dbSNP:rs200727689)" FT /evidence="ECO:0000269|PubMed:8462973" FT /id="VAR_005321" FT VARIANT 168 FT /note="D -> N (in FHCL1; does not affect receptor FT expression at the cell surface; results in reduced LDL FT binding; results in reduced LDL uptake and internalization; FT dbSNP:rs200727689)" FT /evidence="ECO:0000269|PubMed:25545329, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005322" FT VARIANT 168 FT /note="D -> Y (in FHCL1; dbSNP:rs200727689)" FT /evidence="ECO:0000269|PubMed:8740918" FT /id="VAR_005323" FT VARIANT 172 FT /note="D -> H (may contribute to familial FT hypercholesterolemia; dbSNP:rs879254554)" FT /evidence="ECO:0000269|PubMed:10882754" FT /id="VAR_013950" FT VARIANT 172 FT /note="D -> N (in FHCL1; does not affect receptor FT expression at the cell surface; results in reduced LDL FT binding; results in reduced LDL uptake and internalization; FT dbSNP:rs879254554)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:25545329" FT /id="VAR_072832" FT VARIANT 173 FT /note="C -> R (in FHCL1; Greece-1; dbSNP:rs879254558)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005324" FT VARIANT 173 FT /note="C -> W (in FHCL1; dbSNP:rs769318035)" FT /evidence="ECO:0000269|PubMed:9452094" FT /id="VAR_005325" FT VARIANT 175 FT /note="D -> N (in FHCL1; Afrikaner-3; 5-10% of Afrikaners; FT dbSNP:rs121908033)" FT /evidence="ECO:0000269|PubMed:2569482" FT /id="VAR_005326" FT VARIANT 175 FT /note="D -> Y (in FHCL1; dbSNP:rs121908033)" FT /evidence="ECO:0000269|PubMed:9104431" FT /id="VAR_007981" FT VARIANT 177 FT /note="S -> L (in FHCL1; pathogenic; Puerto Rico; FT dbSNP:rs121908026)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:9259195, FT ECO:0000269|PubMed:9654205" FT /id="VAR_005327" FT VARIANT 184 FT /note="C -> W (in FHCL1; dbSNP:rs879254571)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072833" FT VARIANT 184 FT /note="C -> Y (in FHCL1; pathogenic; Glasco; FT dbSNP:rs121908039)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:9678702" FT /id="VAR_013951" FT VARIANT 197 FT /note="C -> F (in FHCL1; likely pathogenic; Shreveport; FT dbSNP:rs376459828)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005328" FT VARIANT 197 FT /note="C -> R (in FHCL1; dbSNP:rs730882085)" FT /evidence="ECO:0000269|PubMed:9026534" FT /id="VAR_005330" FT VARIANT 197 FT /note="C -> Y (in FHCL1; El Salvador-1; dbSNP:rs376459828)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005329" FT VARIANT 201 FT /note="E -> K (in FHCL1; dbSNP:rs879254589)" FT /evidence="ECO:0000269|PubMed:21418584" FT /id="VAR_065781" FT VARIANT 211 FT /note="H -> L (in FHCL1; uncertain significance; FT dbSNP:rs879254603)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072834" FT VARIANT 218 FT /note="Missing (in FHCL1; pathogenic; FT Piscataway/Lithuania)" FT /evidence="ECO:0000269|PubMed:17142622, FT ECO:0000269|PubMed:1867200, ECO:0000269|PubMed:9654205" FT /id="VAR_005331" FT VARIANT 221 FT /note="D -> G (in FHCL1; pathogenic; Padova; FT dbSNP:rs373822756)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910, FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:7649546, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005332" FT VARIANT 221 FT /note="D -> N (in FHCL1; dbSNP:rs875989906)" FT /evidence="ECO:0000269|PubMed:10090484, FT ECO:0000269|PubMed:17142622" FT /id="VAR_007982" FT VARIANT 221 FT /note="D -> Y (in FHCL1; pathogenic; dbSNP:rs875989906)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:7649546" FT /id="VAR_005333" FT VARIANT 222 FT /note="C -> Y (in FHCL1; likely pathogenic; FT dbSNP:rs730882086)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062373" FT VARIANT 224 FT /note="D -> G (in FHCL1; Italy-2; dbSNP:rs879254630)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005335" FT VARIANT 224 FT /note="D -> N (in FHCL1; Portugal; dbSNP:rs387906303)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005334" FT VARIANT 224 FT /note="D -> V (in FHCL1; dbSNP:rs879254630)" FT /evidence="ECO:0000269|PubMed:7649546" FT /id="VAR_005336" FT VARIANT 226 FT /note="S -> P (in FHCL1; Miami-1; dbSNP:rs879254635)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005337" FT VARIANT 227 FT /note="D -> E (in FHCL1; Afrikaner-1/Maine; 65-70% of FT Afrikaner Americans; dbSNP:rs121908028)" FT /evidence="ECO:0000269|PubMed:2569482, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005338" FT VARIANT 228 FT /note="E -> CK (in Chieti-3)" FT /evidence="ECO:0000269|PubMed:10660340" FT /id="VAR_005339" FT VARIANT 228 FT /note="E -> K (in FHCL1; pathogenic; French FT Canadian-3/Mexico; 2% of French Canadians; FT dbSNP:rs121908029)" FT /evidence="ECO:0000269|PubMed:2318961, FT ECO:0000269|PubMed:24529145" FT /id="VAR_005341" FT VARIANT 228 FT /note="E -> Q (in FHCL1; Tulsa-2; dbSNP:rs121908029)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_005340" FT VARIANT 231 FT /note="C -> G (in FHCL1; dbSNP:rs746091400)" FT /evidence="ECO:0000269|PubMed:8664907" FT /id="VAR_005342" FT VARIANT 240 FT /note="E -> K (in FHCL1; pathogenic; Charlotte; FT dbSNP:rs768563000)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005343" FT VARIANT 243 FT /note="C -> R (in FHCL1; likely pathogenic; FT dbSNP:rs879254659)" FT /evidence="ECO:0000269|PubMed:10532689" FT /id="VAR_072835" FT VARIANT 248 FT /note="C -> F (in FHCL1; Bretagne-1; dbSNP:rs879254663)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005344" FT VARIANT 248 FT /note="C -> Y (in FHCL1; dbSNP:rs879254663)" FT /evidence="ECO:0000269|PubMed:9026534" FT /id="VAR_005345" FT VARIANT 253 FT /note="R -> W (in FHCL1; uncertain significance; FT dbSNP:rs150673992)" FT /evidence="ECO:0000269|PubMed:10882754" FT /id="VAR_013952" FT VARIANT 254 FT /note="Q -> P (in FHCL1; dbSNP:rs879254667)" FT /evidence="ECO:0000269|PubMed:10978268, FT ECO:0000269|PubMed:19319977" FT /id="VAR_062374" FT VARIANT 255 FT /note="C -> S (in FHCL1; dbSNP:rs879254668)" FT /evidence="ECO:0000269|PubMed:21418584" FT /id="VAR_065782" FT VARIANT 256 FT /note="D -> G (in FHCL1; Nevers; dbSNP:rs879254670)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005346" FT VARIANT 257 FT /note="R -> W (does not affect receptor expression at the FT cell surface; does not affect LDL binding; does not affect FT LDL uptake and internalization; dbSNP:rs200990725)" FT /evidence="ECO:0000269|PubMed:11462246, FT ECO:0000269|PubMed:25545329" FT /id="VAR_072836" FT VARIANT 261 FT /note="C -> F (in FHCL1; rare mutation; strongly reduced FT receptor activity; dbSNP:rs121908040)" FT /evidence="ECO:0000269|PubMed:10422803" FT /id="VAR_013953" FT VARIANT 266 FT /note="D -> E (in FHCL1; pathogenic; Cincinnati-1; FT dbSNP:rs139043155)" FT /evidence="ECO:0000269|PubMed:1301956, FT ECO:0000269|PubMed:17347910" FT /id="VAR_005347" FT VARIANT 270 FT /note="C -> Y (in FHCL1; Miami-2; dbSNP:rs879254683)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005348" FT VARIANT 276 FT /note="C -> R (in FHCL1; dbSNP:rs879254692)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062375" FT VARIANT 276 FT /note="C -> W (in FHCL1; uncertain significance; FT dbSNP:rs146651743)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072837" FT VARIANT 276 FT /note="C -> Y (in FHCL1; dbSNP:rs730882089)" FT /evidence="ECO:0000269|Ref.73" FT /id="VAR_005349" FT VARIANT 277 FT /note="E -> K (in FHCL1; uncertain significance; FT dbSNP:rs148698650)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:7635461, FT ECO:0000269|PubMed:7649549" FT /id="VAR_005350" FT VARIANT 285 FT /note="H -> Y (in FHCL1; uncertain significance; FT dbSNP:rs730882091)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072838" FT VARIANT 286 FT /note="S -> R (in FHCL1; likely pathogenic; Greece-2; FT dbSNP:rs140241383)" FT /evidence="ECO:0000269|PubMed:1301956, FT ECO:0000269|PubMed:17347910, ECO:0000269|PubMed:9259195" FT /id="VAR_005351" FT VARIANT 288 FT /note="E -> K (in FHCL1; pathogenic; dbSNP:rs368657165)" FT /evidence="ECO:0000269|PubMed:10090484" FT /id="VAR_007983" FT VARIANT 300 FT /note="R -> G (in FHCL1; likely pathogenic; does not affect FT receptor expression at the cell surface; results in reduced FT LDL binding; results in reduced LDL uptake and FT internalization; dbSNP:rs767618089)" FT /evidence="ECO:0000269|PubMed:19318025, FT ECO:0000269|PubMed:25545329" FT /id="VAR_072839" FT VARIANT 301 FT /note="D -> A (in FHCL1; dbSNP:rs879254714)" FT /evidence="ECO:0000269|PubMed:9026534" FT /id="VAR_005352" FT VARIANT 301 FT /note="D -> G (in FHCL1; does not affect receptor FT expression at the cell surface; results in reduced LDL FT binding; results in reduced LDL uptake and internalization; FT dbSNP:rs879254714)" FT /evidence="ECO:0000269|PubMed:19318025, FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:25545329" FT /id="VAR_072840" FT VARIANT 302 FT /note="C -> W (in FHCL1; dbSNP:rs879254716)" FT /evidence="ECO:0000269|PubMed:9026534" FT /id="VAR_005354" FT VARIANT 302 FT /note="C -> Y (in FHCL1; dbSNP:rs879254715)" FT /evidence="ECO:0000269|PubMed:10206683" FT /id="VAR_005353" FT VARIANT 304 FT /note="D -> E (in FHCL1; likely pathogenic; Baltimore-1; FT dbSNP:rs875989909)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005356" FT VARIANT 304 FT /note="D -> N (in FHCL1; pathogenic; Denver-2; FT dbSNP:rs121908030)" FT /evidence="ECO:0000269|PubMed:1301956, FT ECO:0000269|PubMed:21418584" FT /id="VAR_005355" FT VARIANT 306 FT /note="S -> L (in FHCL1; uncertain significance; Amsterdam; FT dbSNP:rs11547917)" FT /evidence="ECO:0000269|PubMed:10532689" FT /id="VAR_005357" FT VARIANT 313 FT /note="C -> Y (in FHCL1; dbSNP:rs875989911 and FT dbSNP:rs875989910)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005358" FT VARIANT 314 FT /note="G -> R (in FHCL1; uncertain significance; FT dbSNP:rs72658858)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072841" FT VARIANT 318 FT /note="C -> F (in FHCL1; Trieste; dbSNP:rs879254739)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:8168830" FT /id="VAR_005360" FT VARIANT 318 FT /note="C -> R (in FHCL1; dbSNP:rs879254738)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062376" FT VARIANT 318 FT /note="C -> Y (in FHCL1; Mexico-1; leads to a defect in the FT intracellular transport of the receptor; FT dbSNP:rs879254739)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005359" FT VARIANT 326 FT /note="S -> C (in FHCL1; pathogenic; dbSNP:rs879254747)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072842" FT VARIANT 327 FT /note="H -> Y (in FHCL1; uncertain significance; FT dbSNP:rs747507019)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005361" FT VARIANT 329 FT /note="C -> F (in FHCL1; dbSNP:rs761954844)" FT /evidence="ECO:0000269|PubMed:22160468" FT /id="VAR_067196" FT VARIANT 329 FT /note="C -> Y (in FHCL1; dbSNP:rs761954844)" FT /evidence="ECO:0000269|PubMed:9452118" FT /id="VAR_005362" FT VARIANT 335 FT /note="G -> S (in FHCL1; likely pathogenic; Paris-6; FT dbSNP:rs544453230)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005363" FT VARIANT 338 FT /note="C -> S (in FHCL1; dbSNP:rs879254753)" FT /evidence="ECO:0000269|PubMed:10447263, FT ECO:0000269|PubMed:7583548" FT /id="VAR_005364" FT VARIANT 342 FT /note="D -> E (in FHCL1; uncertain significance; New FT York-1; dbSNP:rs780563386)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005365" FT VARIANT 342 FT /note="D -> N (in FHCL1; benin; dbSNP:rs139361635)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005366" FT VARIANT 343 FT /note="G -> S (in FHCL1; pathogenic; Picardie; FT dbSNP:rs730882096)" FT /evidence="ECO:0000269|PubMed:1301956, FT ECO:0000269|PubMed:24529145" FT /id="VAR_005367" FT VARIANT 350 FT /note="R -> P (in FHCL1; likely pathogenic; FT dbSNP:rs875989914)" FT /evidence="ECO:0000269|PubMed:9026534, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005368" FT VARIANT 352 FT /note="C -> R (in FHCL1; uncertain significance; FT dbSNP:rs879254769)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072843" FT VARIANT 352 FT /note="C -> Y (in FHCL1; likely pathogenic; Mexico-2; FT dbSNP:rs193922566)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005369" FT VARIANT 354 FT /note="D -> G (in FHCL1; uncertain significance; Munster-2; FT dbSNP:rs755449669)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005370" FT VARIANT 354 FT /note="D -> V (in FHCL1; uncertain significance; Oklahoma; FT dbSNP:rs755449669)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005371" FT VARIANT 356 FT /note="D -> Y (in FHCL1; dbSNP:rs767767730)" FT /evidence="ECO:0000269|PubMed:19319977, FT ECO:0000269|PubMed:9104431" FT /id="VAR_007984" FT VARIANT 357 FT /note="E -> K (in FHCL1; likely pathogenic; Paris-7; FT dbSNP:rs879254781)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005372" FT VARIANT 358 FT /note="C -> Y (in FHCL1; dbSNP:rs875989915)" FT /evidence="ECO:0000269|PubMed:17142622, FT ECO:0000269|PubMed:19319977" FT /id="VAR_062377" FT VARIANT 364 FT /note="C -> R (in FHCL1; uncertain significance; Mexico-3; FT dbSNP:rs879254787)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005373" FT VARIANT 366 FT /note="Q -> R (in FHCL1; dbSNP:rs746982741)" FT /evidence="ECO:0000269|PubMed:8740918" FT /id="VAR_007985" FT VARIANT 368 FT /note="C -> R (in FHCL1; dbSNP:rs879254791)" FT /evidence="ECO:0000269|PubMed:9452094" FT /id="VAR_005374" FT VARIANT 368 FT /note="C -> Y (in FHCL1; uncertain significance; FT dbSNP:rs768430352)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072844" FT VARIANT 370 FT /note="N -> T (in FHCL1; dbSNP:rs879254792)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062378" FT VARIANT 373 FT /note="G -> D (in FHCL1; uncertain significance; FT dbSNP:rs879254797)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072845" FT VARIANT 379 FT /note="C -> R (in FHCL1; uncertain significance; Naples-1; FT dbSNP:rs879254803)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005375" FT VARIANT 379 FT /note="C -> Y (in FHCL1; dbSNP:rs879254804)" FT /evidence="ECO:0000269|PubMed:9852677" FT /id="VAR_007986" FT VARIANT 391 FT /note="A -> T (in dbSNP:rs11669576)" FT /id="VAR_024519" FT VARIANT 399 FT /note="A -> D (in FHCL1; dbSNP:rs875989918)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005376" FT VARIANT 401 FT /note="L -> H (in FHCL1; uncertain significance; Pori; FT dbSNP:rs121908038)" FT /evidence="ECO:0000269|PubMed:7573037" FT /id="VAR_005377" FT VARIANT 401 FT /note="L -> V (in FHCL1; dbSNP:rs146200173)" FT /evidence="ECO:0000269|PubMed:9104431" FT /id="VAR_007987" FT VARIANT 403 FT /note="F -> L (in FHCL1; dbSNP:rs879254831)" FT /evidence="ECO:0000269|PubMed:10447263" FT /id="VAR_008995" FT VARIANT 404 FT /note="T -> P (in FHCL1; uncertain significance; FT dbSNP:rs879254834)" FT /evidence="ECO:0000269|PubMed:10532689" FT /id="VAR_072846" FT VARIANT 406 FT /note="R -> Q (may contribute to familial FT hypercholesterolemia; dbSNP:rs552422789)" FT /evidence="ECO:0000269|PubMed:10882754" FT /id="VAR_013954" FT VARIANT 406 FT /note="R -> W (in FHCL1; pathogenic; dbSNP:rs121908043)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072847" FT VARIANT 408 FT /note="E -> K (in FHCL1; uncertain significance; Algeria-1; FT dbSNP:rs137943601)" FT /evidence="ECO:0000269|PubMed:10882754, FT ECO:0000269|PubMed:17347910" FT /id="VAR_005378" FT VARIANT 414 FT /note="L -> R (in FHCL1; uncertain significance; FT dbSNP:rs748554592)" FT /evidence="ECO:0000269|PubMed:9452118" FT /id="VAR_005379" FT VARIANT 415 FT /note="D -> G (in FHCL1; uncertain significance; FT dbSNP:rs879254845)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062379" FT VARIANT 416 FT /note="R -> Q (in FHCL1; uncertain significance; FT dbSNP:rs773658037)" FT /evidence="ECO:0000269|PubMed:9452095" FT /id="VAR_005380" FT VARIANT 416 FT /note="R -> W (in FHCL1; results in reduced receptor FT expression at the cell surface due to defective receptor FT recycling; dbSNP:rs570942190)" FT /evidence="ECO:0000269|PubMed:19318025, FT ECO:0000269|PubMed:25378237, ECO:0000269|PubMed:9104431, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005381" FT VARIANT 423 FT /note="I -> T (in FHCL1; dbSNP:rs879254849)" FT /evidence="ECO:0000269|PubMed:7635461" FT /id="VAR_005382" FT VARIANT 429 FT /note="V -> M (in FHCL1; Afrikaner-2; 20-30% of Afrikaners FT and 2% of FHCL1 Dutch; dbSNP:rs28942078)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:2569482, ECO:0000269|PubMed:7649549, FT ECO:0000269|PubMed:9452095, ECO:0000269|PubMed:9452118" FT /id="VAR_005383" FT VARIANT 431 FT /note="A -> T (in FHCL1; uncertain significance; Algeria-2; FT dbSNP:rs28942079)" FT /evidence="ECO:0000269|PubMed:10447263, FT ECO:0000269|PubMed:17347910" FT /id="VAR_005384" FT VARIANT 432 FT /note="L -> V (in FHCL1; dbSNP:rs730882100)" FT /evidence="ECO:0000269|PubMed:10090484" FT /id="VAR_007988" FT VARIANT 433 FT /note="D -> H (in FHCL1; Osaka-3; dbSNP:rs121908036)" FT /evidence="ECO:0000269|PubMed:1446662" FT /id="VAR_005385" FT VARIANT 434 FT /note="T -> K (in FHCL1; likely pathogenic; Algeria-3; FT dbSNP:rs745343524)" FT /evidence="ECO:0000269|PubMed:10206683" FT /id="VAR_005386" FT VARIANT 441 FT /note="I -> M (in FHCL1; uncertain significance; Rouen; FT dbSNP:rs5933)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005388" FT VARIANT 441 FT /note="I -> N (in FHCL1; uncertain significance; Russia-1; FT dbSNP:rs879254862)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005387" FT VARIANT 442 FT /note="Y -> H (in FHCL1; uncertain significance; FT dbSNP:rs879254863)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072848" FT VARIANT 443 FT /note="W -> C (in FHCL1; North Platt; dbSNP:rs879254867)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005389" FT VARIANT 451 FT /note="I -> T (in FHCL1; dbSNP:rs879254874)" FT /evidence="ECO:0000269|PubMed:10980548, FT ECO:0000269|PubMed:19319977" FT /id="VAR_062380" FT VARIANT 454 FT /note="T -> N (in FHCL1; likely pathogenic; results in FT reduced receptor expression at the cell surface due to FT defective receptor recycling; dbSNP:rs879254879)" FT /evidence="ECO:0000269|PubMed:19318025, FT ECO:0000269|PubMed:25378237" FT /id="VAR_072849" FT VARIANT 468 FT /note="V -> I (in dbSNP:rs5932)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_011863" FT VARIANT 471 FT /note="R -> G (in FHCL1; uncertain significance; FT dbSNP:rs879254891)" FT /evidence="ECO:0000269|PubMed:21418584" FT /id="VAR_065783" FT VARIANT 478 FT /note="G -> R (in FHCL1; pathogenic; New York-2; FT dbSNP:rs144614838)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005390" FT VARIANT 479 FT /note="L -> P (in FHCL1; dbSNP:rs879254900)" FT /evidence="ECO:0000269|PubMed:17142622" FT /id="VAR_062381" FT VARIANT 482 FT /note="D -> H (in FHCL1; dbSNP:rs139624145)" FT /evidence="ECO:0000269|PubMed:17142622, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005391" FT VARIANT 483 FT /note="W -> R (in FHCL1; uncertain significance; FT dbSNP:rs879254905)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005392" FT VARIANT 485 FT /note="H -> R (in FHCL1; Milan; dbSNP:rs879254906)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005394" FT VARIANT 487 FT /note="Missing (in FHCL1)" FT /evidence="ECO:0000269|PubMed:7635482" FT /id="VAR_005393" FT VARIANT 492 FT /note="D -> N (in FHCL1; uncertain significance; FT dbSNP:rs373646964)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072850" FT VARIANT 523 FT /note="V -> M (in FHCL1; Kuwait; dbSNP:rs28942080)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_005395" FT VARIANT 526 FT /note="P -> S (in FHCL1; uncertain significance; FT Cincinnati-3; dbSNP:rs730882106)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005396" FT VARIANT 546 FT /note="G -> D (in Saint Omer; retention in the ER; FT dbSNP:rs28942081)" FT /evidence="ECO:0000269|PubMed:19520913" FT /id="VAR_005397" FT VARIANT 549 FT /note="G -> D (in FHCL1; Genoa; dbSNP:rs28941776)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005398" FT VARIANT 564 FT /note="N -> H (in FHCL1; dbSNP:rs397509365)" FT /evidence="ECO:0000269|PubMed:10090484, FT ECO:0000269|PubMed:10532689, ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:7550239, ECO:0000269|PubMed:9143924" FT /id="VAR_005399" FT VARIANT 564 FT /note="N -> S (in FHCL1; Sicily; dbSNP:rs758194385)" FT /evidence="ECO:0000269|PubMed:9654205" FT /id="VAR_005400" FT VARIANT 565 FT /note="G -> V (in FHCL1; Naples-2; dbSNP:rs28942082)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005401" FT VARIANT 568 FT /note="L -> V (in FHCL1; dbSNP:rs746959386)" FT /evidence="ECO:0000269|PubMed:10447263" FT /id="VAR_008996" FT VARIANT 574 FT /note="R -> C (in FHCL1; uncertain significance1; FT dbSNP:rs185098634)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072851" FT VARIANT 574 FT /note="R -> H (in FHCL1; likely pathogenic; FT dbSNP:rs777188764)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072852" FT VARIANT 577 FT /note="W -> G (in FHCL1; pathogenic; results in loss of FT receptor expression at the cell surface; FT dbSNP:rs879255000)" FT /evidence="ECO:0000269|PubMed:17347910, FT ECO:0000269|PubMed:25378237" FT /id="VAR_072853" FT VARIANT 577 FT /note="W -> S (in FHCL1; uncertain significance; FT dbSNP:rs138947766)" FT /evidence="ECO:0000269|PubMed:10532689" FT /id="VAR_072854" FT VARIANT 579 FT /note="D -> N (in FHCL1; Cincinnati-4; less than 2% FT receptor activity; dbSNP:rs875989929)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:7635461" FT /id="VAR_005402" FT VARIANT 579 FT /note="D -> Y (in FHCL1; dbSNP:rs875989929)" FT /evidence="ECO:0000269|PubMed:10978268" FT /id="VAR_062382" FT VARIANT 585 FT /note="I -> T (in FHCL1; uncertain significance; FT dbSNP:rs879255012)" FT /evidence="ECO:0000269|PubMed:17347910" FT /id="VAR_072855" FT VARIANT 592 FT /note="G -> E (in FHCL1; pathogenic; Sicily; FT dbSNP:rs137929307)" FT /evidence="ECO:0000269|PubMed:9654205" FT /id="VAR_005403" FT VARIANT 595 FT /note="R -> W (in FHCL1; pathogenic; dbSNP:rs373371572)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072856" FT VARIANT 599 FT /note="L -> S (in FHCL1; uncertain significance; London-5; FT dbSNP:rs879255025)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005404" FT VARIANT 601 FT /note="D -> H (in FHCL1; uncertain significance; FT dbSNP:rs753707206)" FT /evidence="ECO:0000269|PubMed:24529145" FT /id="VAR_072857" FT VARIANT 608 FT /note="P -> S (in FHCL1; dbSNP:rs879255034)" FT /evidence="ECO:0000269|PubMed:9852677" FT /id="VAR_007989" FT VARIANT 633 FT /note="R -> C (in FHCL1; dbSNP:rs746118995)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005405" FT VARIANT 639 FT /note="V -> D (in FHCL1; dbSNP:rs794728584)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072858" FT VARIANT 649 FT /note="P -> L (in FHCL1; dbSNP:rs879255081)" FT /evidence="ECO:0000269|PubMed:9259195" FT /id="VAR_005406" FT VARIANT 667 FT /note="C -> Y (in FHCL1; likely pathogenic; French FT Canadian-2; 5% of French Canadians; dbSNP:rs28942083)" FT /evidence="ECO:0000269|PubMed:10206683, FT ECO:0000269|PubMed:2318961" FT /id="VAR_005407" FT VARIANT 677 FT /note="C -> R (in FHCL1; New York-3; dbSNP:rs775092314)" FT /evidence="ECO:0000269|PubMed:17142622" FT /id="VAR_005408" FT VARIANT 682 FT /note="L -> P (in FHCL1; uncertain significance; Issoire; FT dbSNP:rs879255119)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005409" FT VARIANT 685 FT /note="P -> L (in FHCL1; FT Gujerat/Zambia/Belgian/Dutch/Sweden/Japan; FT dbSNP:rs28942084)" FT /evidence="ECO:0000269|PubMed:1464748, FT ECO:0000269|PubMed:17142622, ECO:0000269|PubMed:17347910, FT ECO:0000269|PubMed:24529145, ECO:0000269|PubMed:2726768, FT ECO:0000269|PubMed:7583548, ECO:0000269|PubMed:9254862" FT /id="VAR_005410" FT VARIANT 699 FT /note="P -> L (in FHCL1; uncertain significance; FT dbSNP:rs201573863)" FT /evidence="ECO:0000269|PubMed:10882754, FT ECO:0000269|PubMed:24529145" FT /id="VAR_013955" FT VARIANT 700 FT /note="D -> E (in FHCL1; uncertain significance; FT dbSNP:rs759858813)" FT /evidence="ECO:0000269|PubMed:10206683" FT /id="VAR_005412" FT VARIANT 714 FT /note="E -> K (in FHCL1; dbSNP:rs869320652)" FT /evidence="ECO:0000269|PubMed:10447263" FT /id="VAR_008997" FT VARIANT 726 FT /note="T -> I (in FHCL1; benign; Paris-9; FT dbSNP:rs45508991)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:9259195" FT /id="VAR_005413" FT VARIANT 742 FT /note="T -> I (in dbSNP:rs767546791)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072859" FT VARIANT 792 FT /note="I -> F (in FHCL1; uncertain significance; Russia-2; FT dbSNP:rs761123215)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005414" FT VARIANT 797 FT /note="V -> M (in FHCL1; dbSNP:rs750518671)" FT /evidence="ECO:0000269|PubMed:24529145, FT ECO:0000269|PubMed:7649549" FT /id="VAR_005415" FT VARIANT 799..801 FT /note="Missing (in FHCL1; dbSNP:rs879255195)" FT /evidence="ECO:0000269|PubMed:9143924" FT /id="VAR_005416" FT VARIANT 806 FT /note="V -> D (in FHCL1; uncertain significance; FT dbSNP:rs879255208)" FT /evidence="ECO:0000269|PubMed:11462246" FT /id="VAR_072860" FT VARIANT 814 FT /note="R -> Q (in FHCL1; uncertain significance; FT dbSNP:rs5928)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10882754, ECO:0000269|PubMed:24529145" FT /id="VAR_011864" FT VARIANT 820..822 FT /note="Missing (in FHCL1)" FT /id="VAR_005417" FT VARIANT 825 FT /note="N -> K (in FHCL1; pathogenic; does not affect FT receptor expression at the cell surface; does not affect FT LDL binding; results in impaired LDL uptake and FT internalization; dbSNP:rs374045590)" FT /evidence="ECO:0000269|PubMed:10532689, FT ECO:0000269|PubMed:25378237" FT /id="VAR_072861" FT VARIANT 826 FT /note="P -> S (in FHCL1; dbSNP:rs879255217)" FT /evidence="ECO:0000269|PubMed:19319977" FT /id="VAR_062383" FT VARIANT 827 FT /note="V -> I (in FHCL1; uncertain significance; New FT York-5; dbSNP:rs137853964)" FT /evidence="ECO:0000269|PubMed:1301956" FT /id="VAR_005418" FT VARIANT 828 FT /note="Y -> C (in FHCL1; J.D.Bari/Syria; 2-fold decreased FT affinity for LDLRAP1; dbSNP:rs28942085)" FT /evidence="ECO:0000269|PubMed:22509010, FT ECO:0000269|PubMed:3955657" FT /id="VAR_005419" FT VARIANT 844 FT /note="G -> D (in FHCL1; likely pathogenic; Turku; FT dbSNP:rs121908037)" FT /evidence="ECO:0000269|PubMed:7573037" FT /id="VAR_005420" FT MUTAGEN 811 FT /note="K->R: No change. No change; when associated with FT R-816 and R-830. Insensitive to MYLIP-triggered FT degradation; when associated with R-816; R-830 and A-839." FT /evidence="ECO:0000269|PubMed:19520913" FT MUTAGEN 816 FT /note="K->R: No change. No change; when associated with FT R-830. No change; when associated with R-811 and R-830. FT Insensitive to MYLIP-triggered degradation; when associated FT with R-830 and A-839. Insensitive to MYLIP-triggered FT degradation; when associated with R-811; R-830 and A-839." FT /evidence="ECO:0000269|PubMed:19520913" FT MUTAGEN 821 FT /note="I->A: 3-fold decreased affinity for LDLRAP1." FT /evidence="ECO:0000269|PubMed:22509010" FT MUTAGEN 821 FT /note="I->R: 10-fold decreased affinity for LDLRAP1." FT /evidence="ECO:0000269|PubMed:22509010" FT MUTAGEN 828 FT /note="Y->A: Abolishes interaction with ARRB2." FT /evidence="ECO:0000269|PubMed:12944399" FT MUTAGEN 829 FT /note="Q->A: Decreased affinity for LDLRAP1." FT /evidence="ECO:0000269|PubMed:22509010" FT MUTAGEN 830 FT /note="K->R: No change. No change; when associated with FT R-816. No change; when associated with R-811 and R-816. FT Insensitive to MYLIP-triggered degradation; when associated FT with A-839. Insensitive to MYLIP-triggered degradation; FT when associated with R-816 and A-839. Insensitive to FT MYLIP-triggered degradation; when associated with R-811; FT R-816 and A-839." FT /evidence="ECO:0000269|PubMed:19520913" FT MUTAGEN 839 FT /note="C->A: No change. Insensitive to MYLIP-triggered FT degradation; when associated with R-830. Insensitive to FT MYLIP-triggered degradation; when associated with R-816 and FT R-830. Insensitive to MYLIP-triggered degradation; when FT associated with R-811; R-816 and R-830." FT /evidence="ECO:0000269|PubMed:19520913" FT MUTAGEN 854 FT /note="S->A: No effect on receptor internalization." FT /evidence="ECO:0000269|PubMed:12944399" FT MUTAGEN 854 FT /note="S->D: Enhances interaction with ARRB2 and receptor FT internalization." FT /evidence="ECO:0000269|PubMed:12944399" FT CONFLICT 31 FT /note="E -> D (in Ref. 4; BAG58495)" FT /evidence="ECO:0000305" FT STRAND 29..33 FT /evidence="ECO:0007829|PDB:1F5Y" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:1F5Y" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:1LDL" FT TURN 42..46 FT /evidence="ECO:0007829|PDB:1F5Y" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:1F5Y" FT STRAND 51..55 FT /evidence="ECO:0007829|PDB:1F5Y" FT HELIX 56..58 FT /evidence="ECO:0007829|PDB:1F5Y" FT TURN 60..62 FT /evidence="ECO:0007829|PDB:1LDL" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:5OYL" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:1LDR" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:5OYL" FT HELIX 85..87 FT /evidence="ECO:0007829|PDB:5OYL" FT STRAND 90..93 FT /evidence="ECO:0007829|PDB:5OYL" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:1F5Y" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:5OYL" FT STRAND 102..104 FT /evidence="ECO:0007829|PDB:5OYL" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:2FCW" FT STRAND 121..123 FT /evidence="ECO:0007829|PDB:2FCW" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:2FCW" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:2FCW" FT TURN 138..142 FT /evidence="ECO:0007829|PDB:2FCW" FT HELIX 143..147 FT /evidence="ECO:0007829|PDB:2FCW" FT STRAND 148..151 FT /evidence="ECO:0007829|PDB:2LGP" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:2FCW" FT TURN 156..158 FT /evidence="ECO:0007829|PDB:2LGP" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:2FCW" FT HELIX 163..165 FT /evidence="ECO:0007829|PDB:2FCW" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:2FCW" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:2LGP" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:2FCW" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:2FCW" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:2LGP" FT STRAND 201..204 FT /evidence="ECO:0007829|PDB:2LGP" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:2LGP" FT STRAND 208..211 FT /evidence="ECO:0007829|PDB:2LGP" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:1AJJ" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:1AJJ" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:2LGP" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:1AJJ" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:1D2J" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:1D2J" FT STRAND 247..249 FT /evidence="ECO:0007829|PDB:1D2J" FT HELIX 251..253 FT /evidence="ECO:0007829|PDB:1D2J" FT STRAND 254..258 FT /evidence="ECO:0007829|PDB:1D2J" FT STRAND 260..264 FT /evidence="ECO:0007829|PDB:1D2J" FT HELIX 265..267 FT /evidence="ECO:0007829|PDB:1F8Z" FT STRAND 268..270 FT /evidence="ECO:0007829|PDB:1F8Z" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:1XFE" FT STRAND 289..292 FT /evidence="ECO:0007829|PDB:1XFE" FT TURN 293..296 FT /evidence="ECO:0007829|PDB:1XFE" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:1XFE" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:1XFE" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:2W2N" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:2W2N" FT STRAND 326..330 FT /evidence="ECO:0007829|PDB:2W2N" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:2W2N" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:2W2N" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:1HZ8" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:2W2N" FT TURN 348..350 FT /evidence="ECO:0007829|PDB:2W2N" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:2W2N" FT HELIX 357..359 FT /evidence="ECO:0007829|PDB:1HJ7" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:1HJ7" FT STRAND 372..374 FT /evidence="ECO:0007829|PDB:3P5B" FT STRAND 376..378 FT /evidence="ECO:0007829|PDB:1HJ7" FT STRAND 381..385 FT /evidence="ECO:0007829|PDB:1HZ8" FT TURN 387..389 FT /evidence="ECO:0007829|PDB:3P5B" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:1HZ8" FT STRAND 400..404 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 406..413 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 420..423 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 427..435 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 436..439 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 440..445 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 446..449 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 450..455 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 466..469 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 478..482 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 483..486 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 487..492 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 493..496 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 497..502 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 505..513 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 519..525 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 526..529 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 530..535 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 537..539 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 541..546 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 552..556 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 563..569 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 570..573 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 574..579 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 580..583 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 584..589 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 596..600 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 602..605 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 606..614 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 617..622 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 623..626 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 627..632 FT /evidence="ECO:0007829|PDB:1IJQ" FT TURN 633..635 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 640..643 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 652..656 FT /evidence="ECO:0007829|PDB:1IJQ" FT HELIX 657..659 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 668..672 FT /evidence="ECO:0007829|PDB:1IJQ" FT HELIX 673..676 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 678..683 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 693..697 FT /evidence="ECO:0007829|PDB:1IJQ" FT STRAND 708..713 FT /evidence="ECO:0007829|PDB:3P5B" FT STRAND 821..824 FT /evidence="ECO:0007829|PDB:3SO6" FT TURN 826..829 FT /evidence="ECO:0007829|PDB:3SO6" SQ SEQUENCE 860 AA; 95376 MW; A4C28E9B8BADAD5E CRC64; MGPWGWKLRW TVALLLAAAG TAVGDRCERN EFQCQDGKCI SYKWVCDGSA ECQDGSDESQ ETCLSVTCKS GDFSCGGRVN RCIPQFWRCD GQVDCDNGSD EQGCPPKTCS QDEFRCHDGK CISRQFVCDS DRDCLDGSDE ASCPVLTCGP ASFQCNSSTC IPQLWACDND PDCEDGSDEW PQRCRGLYVF QGDSSPCSAF EFHCLSGECI HSSWRCDGGP DCKDKSDEEN CAVATCRPDE FQCSDGNCIH GSRQCDREYD CKDMSDEVGC VNVTLCEGPN KFKCHSGECI TLDKVCNMAR DCRDWSDEPI KECGTNECLD NNGGCSHVCN DLKIGYECLC PDGFQLVAQR RCEDIDECQD PDTCSQLCVN LEGGYKCQCE EGFQLDPHTK ACKAVGSIAY LFFTNRHEVR KMTLDRSEYT SLIPNLRNVV ALDTEVASNR IYWSDLSQRM ICSTQLDRAH GVSSYDTVIS RDIQAPDGLA VDWIHSNIYW TDSVLGTVSV ADTKGVKRKT LFRENGSKPR AIVVDPVHGF MYWTDWGTPA KIKKGGLNGV DIYSLVTENI QWPNGITLDL LSGRLYWVDS KLHSISSIDV NGGNRKTILE DEKRLAHPFS LAVFEDKVFW TDIINEAIFS ANRLTGSDVN LLAENLLSPE DMVLFHNLTQ PRGVNWCERT TLSNGGCQYL CLPAPQINPH SPKFTCACPD GMLLARDMRS CLTEAEAAVA TQETSTVRLK VSSTAVRTQH TTTRPVPDTS RLPGATPGLT TVEIVTMSHQ ALGDVAGRGN EKKPSSVRAL SIVLPIVLLV FLCLGVFLLW KNWRLKNINS INFDNPVYQK TTEDEVHICH NQDGYSYPSR QMVSLEDDVA //