Low-density lipoprotein receptor

NameLow-density lipoprotein receptor
Synonyms
  • LDL receptor
Gene NameLDLR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000996|Low-density lipoprotein receptor
MGPWGWKLRWTVALLLAAAGTAVGDRCERNEFQCQDGKCISYKWVCDGSAECQDGSDESQ
ETCLSVTCKSGDFSCGGRVNRCIPQFWRCDGQVDCDNGSDEQGCPPKTCSQDEFRCHDGK
CISRQFVCDSDRDCLDGSDEASCPVLTCGPASFQCNSSTCIPQLWACDNDPDCEDGSDEW
PQRCRGLYVFQGDSSPCSAFEFHCLSGECIHSSWRCDGGPDCKDKSDEENCAVATCRPDE
FQCSDGNCIHGSRQCDREYDCKDMSDEVGCVNVTLCEGPNKFKCHSGECITLDKVCNMAR
DCRDWSDEPIKECGTNECLDNNGGCSHVCNDLKIGYECLCPDGFQLVAQRRCEDIDECQD
PDTCSQLCVNLEGGYKCQCEEGFQLDPHTKACKAVGSIAYLFFTNRHEVRKMTLDRSEYT
SLIPNLRNVVALDTEVASNRIYWSDLSQRMICSTQLDRAHGVSSYDTVISRDIQAPDGLA
VDWIHSNIYWTDSVLGTVSVADTKGVKRKTLFRENGSKPRAIVVDPVHGFMYWTDWGTPA
KIKKGGLNGVDIYSLVTENIQWPNGITLDLLSGRLYWVDSKLHSISSIDVNGGNRKTILE
DEKRLAHPFSLAVFEDKVFWTDIINEAIFSANRLTGSDVNLLAENLLSPEDMVLFHNLTQ
PRGVNWCERTTLSNGGCQYLCLPAPQINPHSPKFTCACPDGMLLARDMRSCLTEAEAAVA
TQETSTVRLKVSSTAVRTQHTTTRPVPDTSRLPGATPGLTTVEIVTMSHQALGDVAGRGN
EKKPSSVRALSIVLPIVLLVFLCLGVFLLWKNWRLKNINSINFDNPVYQKTTEDEVHICH
NQDGYSYPSRQMVSLEDDVA
Number of residues860
Molecular Weight95375.105
Theoretical pI4.64
GO Classification
Functions
  • very-low-density lipoprotein particle receptor activity
  • clathrin heavy chain binding
  • protease binding
  • receptor activity
  • calcium ion binding
  • glycoprotein binding
  • low-density lipoprotein particle binding
  • virus receptor activity
  • low-density lipoprotein receptor activity
Processes
  • phospholipid transport
  • positive regulation of triglyceride biosynthetic process
  • regulation of phosphatidylcholine catabolic process
  • small molecule metabolic process
  • regulation of cholesterol homeostasis
  • retinoid metabolic process
  • receptor-mediated endocytosis
  • lipid metabolic process
  • endocytosis
  • phototransduction, visible light
  • cholesterol homeostasis
  • cholesterol metabolic process
  • lipoprotein metabolic process
  • cholesterol transport
  • intestinal cholesterol absorption
  • lipoprotein catabolic process
  • cholesterol import
  • low-density lipoprotein particle clearance
Components
  • coated pit
  • Golgi apparatus
  • PCSK9-LDLR complex
  • external side of plasma membrane
  • integral component of plasma membrane
  • apical part of cell
  • late endosome
  • basolateral plasma membrane
  • membrane
  • early endosome
  • endosome membrane
  • plasma membrane
  • clathrin-coated endocytic vesicle membrane
  • receptor complex
  • low-density lipoprotein particle
  • lysosome
  • cell surface
General FunctionVirus receptor activity
Specific FunctionBinds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.(Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins (PubMed:10535997, PubMed:12615904). Acts as a receptor for vesicular stomatitis virus (PubMed:23589850). In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells (PubMed:11100124).
Pfam Domain Function
Transmembrane Regions789-810
GenBank Protein ID307121
UniProtKB IDP01130
UniProtKB Entry NameLDLR_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0018965|Low-density lipoprotein receptor (LDLR)
ATGGGGCCCTGGGGCTGGAAATTGCGCTGGACCGTCGCCTTGCTCCTCGCCGCGGCGGGG
ACTGCAGTGGGCGACAGATGCGAAAGAAACGAGTTCCAGTGCCAAGACGGGAAATGCATC
TCCTACAAGTGGGTCTGCGATGGCAGCGCTGAGTGCCAGGATGGCTCTGATGAGTCCCAG
GAGACGTGCTTGTCTGTCACCTGCAAATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAAC
CGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACAACGGCTCAGAC
GAGCAAGGCTGTCCCCCCAAGACGTGCTCCCAGGACGAGTTTCGCTGCCACGATGGGAAG
TGCATCTCTCGGCAGTTCGTCTGTGACTCAGACCGGGACTGCTTGGACGGCTCAGACGAG
GCCTCCTGCCCGGTGCTCACCTGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGC
ATCCCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGTGG
CCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGGACAGTAGCCCCTGCTCGGCCTTC
GAGTTCCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGGCCCC
GACTGCAAGGACAAATCTGACGAGGAAAACTGCGCTGTGGCCACCTGTCGCCCTGACGAA
TTCCAGTGCTCTGATGGAAACTGCATCCATGGCAGCCGGCAGTGTGACCGGGAATATGAC
TGCAAGGACATGAGCGATGAAGTTGGCTGCGTTAATGTGACACTCTGCGAGGGACCCAAC
AAGTTCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAAAGTCTGCAACATGGCTAGA
GACTGCCGGGACTGGTCAGATGAACCCATCAAAGAGTGCGGGACCAACGAATGCTTGGAC
AACAACGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGCTACGAGTGCCTGTGC
CCCGACGGCTTCCAGCTGGTGGCCCAGCGAAGATGCGAAGATATCGATGAGTGTCAGGAT
CCCGACACCTGCAGCCAGCTCTGCGTGAACCTGGAGGGTGGCTACAAGTGCCAGTGTGAG
GAAGGCTTCCAGCTGGACCCCCACACGAAGGCCTGCAAGGCTGTGGGCTCCATCGCCTAC
CTCTTCTTCACCAACCGGCACGAGGTCAGGAAGATGACGCTGGACCGGAGCGAGTACACC
AGCCTCATCCCCAACCTGAGGAACGTGGTCGCTCTGGACACGGAGGTGGCCAGCAATAGA
ATCTACTGGTCTGACCTGTCCCAGAGAATGATCTGCAGCACCCAGCTTGACAGAGCCCAC
GGCGTCTCTTCCTATGACACCGTCATCAGCAGAGACATCCAGGCCCCCGACGGGCTGGCT
GTGGACTGGATCCACAGCAACATCTACTGGACCGACTCTGTCCTGGGCACTGTCTCTGTT
GCGGATACCAAGGGCGTGAAGAGGAAAACGTTATTCAGGGAGAACGGCTCCAAGCCAAGG
GCCATCGTGGTGGATCCTGTTCATGGCTTCATGTACTGGACTGACTGGGGAACTCCCGCC
AAGATCAAGAAAGGGGGCCTGAATGGTGTGGACATCTACTCGCTGGTGACTGAAAACATT
CAGTGGCCCAATGGCATCACCCTAGATCTCCTCAGTGGCCGCCTCTACTGGGTTGACTCC
AAACTTCACTCCATCTCAAGCATCGATGTCAACGGGGGCAACCGGAAGACCATCTTGGAG
GATGAAAAGAGGCTGGCCCACCCCTTCTCCTTGGCCGTCTTTGAGGACAAAGTATTTTGG
ACAGATATCATCAACGAAGCCATTTTCAGTGCCAACCGCCTCACAGGTTCCGATGTCAAC
TTGTTGGCTGAAAACCTACTGTCCCCAGAGGATATGGTTCTCTTCCACAACCTCACCCAG
CCAAGAGGAGTGAACTGGTGTGAGAGGACCACCCTGAGCAATGGCGGCTGCCAGTATCTG
TGCCTCCCTGCCCCGCAGATCAACCCCCACTCGCCCAAGTTTACCTGCGCCTGCCCGGAC
GGCATGCTGCTGGCCAGGGACATGAGGAGCTGCCTCACAGAGGCTGAGGCTGCAGTGGCC
ACCCAGGAGACATCCACCGTCAGGCTAAAGGTCAGCTCCACAGCCGTAAGGACACAGCAC
ACAACCACCCGACCTGTTCCCGACACCTCCCGGCTGCCTGGGGCCACCCCTGGGCTCACC
ACGGTGGAGATAGTGACAATGTCTCACCAAGCTCTGGGCGACGTTGCTGGCAGAGGAAAT
GAGAAGAAGCCCAGTAGCGTGAGGGCTCTGTCCATTGTCCTCCCCATCGTGCTCCTCGTC
TTCCTTTGCCTGGGGGTCTTCCTTCTATGGAAGAACTGGCGGCTTAAGAACATCAACAGC
ATCAACTTTGACAACCCCGTCTATCAGAAGACCACAGAGGATGAGGTCCACATTTGCCAC
AACCAGGACGGCTACAGCTACCCCTCGAGACAGATGGTCAGTCTGGAGGATGACGTGGCG
TGA
GenBank Gene IDL00352
GeneCard IDNot Available
GenAtlas IDLDLR
HGNC IDHGNC:6547
Chromosome Location19
Locus19p13.3
References
  1. Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW: The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell. 1984 Nov;39(1):27-38. 6091915
  2. Sudhof TC, Goldstein JL, Brown MS, Russell DW: The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815-22. 2988123
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Hofer F, Gruenberger M, Kowalski H, Machat H, Huettinger M, Kuechler E, Blaas D: Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1839-42. 8127891
  7. Davis CG, Elhammer A, Russell DW, Schneider WJ, Kornfeld S, Brown MS, Goldstein JL: Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts. J Biol Chem. 1986 Feb 25;261(6):2828-38. 3005267
  8. Davis CG, van Driel IR, Russell DW, Brown MS, Goldstein JL: The low density lipoprotein receptor. Identification of amino acids in cytoplasmic domain required for rapid endocytosis. J Biol Chem. 1987 Mar 25;262(9):4075-82. 3104336
  9. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX: Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71. 10535997
  10. Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ: Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med. 2000 Dec;6(12):1380-7. 11100124
  11. He G, Gupta S, Yi M, Michaely P, Hobbs HH, Cohen JC: ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem. 2002 Nov 15;277(46):44044-9. Epub 2002 Sep 8. 12221107
  12. Wu JH, Peppel K, Nelson CD, Lin FT, Kohout TA, Miller WE, Exum ST, Freedman NJ: The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor. J Biol Chem. 2003 Nov 7;278(45):44238-45. Epub 2003 Aug 27. 12944399
  13. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. 12754519
  14. Bartosch B, Dubuisson J, Cosset FL: Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med. 2003 Mar 3;197(5):633-42. 12615904
  15. Burden JJ, Sun XM, Garcia AB, Soutar AK: Sorting motifs in the intracellular domain of the low density lipoprotein receptor interact with a novel domain of sorting nexin-17. J Biol Chem. 2004 Apr 16;279(16):16237-45. Epub 2004 Jan 22. 14739284
  16. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  17. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  18. Nassoury N, Blasiole DA, Tebon Oler A, Benjannet S, Hamelin J, Poupon V, McPherson PS, Attie AD, Prat A, Seidah NG: The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic. 2007 Jun;8(6):718-32. Epub 2007 Apr 25. 17461796
  19. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. 19159218
  20. Zelcer N, Hong C, Boyadjian R, Tontonoz P: LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009 Jul 3;325(5936):100-4. doi: 10.1126/science.1168974. Epub 2009 Jun 11. 19520913
  21. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  22. Yamamoto T, Lu C, Ryan RO: A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor. J Biol Chem. 2011 Feb 18;286(7):5464-70. doi: 10.1074/jbc.M110.199042. Epub 2010 Dec 11. 21149300
  23. Finkelshtein D, Werman A, Novick D, Barak S, Rubinstein M: LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7306-11. doi: 10.1073/pnas.1214441110. Epub 2013 Apr 15. 23589850
  24. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  25. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  26. Daly NL, Scanlon MJ, Djordjevic JT, Kroon PA, Smith R: Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6334-8. 7603991
  27. Daly NL, Djordjevic JT, Kroon PA, Smith R: Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor. Biochemistry. 1995 Nov 7;34(44):14474-81. 7578052
  28. Fass D, Blacklow S, Kim PS, Berger JM: Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature. 1997 Aug 14;388(6643):691-3. 9262405
  29. Kurniawan ND, Atkins AR, Bieri S, Brown CJ, Brereton IM, Kroon PA, Smith R: NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor. Protein Sci. 2000 Jul;9(7):1282-93. 10933493
  30. Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown MS, Goldstein JL, Deisenhofer J: Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002 Dec 20;298(5602):2353-8. Epub 2002 Nov 29. 12459547
  31. Hobbs HH, Brown MS, Goldstein JL: Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat. 1992;1(6):445-66. 1301956
  32. Varret M, Rabes JP, Collod-Beroud G, Junien C, Boileau C, Beroud C: Software and database for the analysis of mutations in the human LDL receptor gene. Nucleic Acids Res. 1997 Jan 1;25(1):172-80. 9016531
  33. Leitersdorf E, Hobbs HH, Fourie AM, Jacobs M, van der Westhuyzen DR, Coetzee GA: Deletion in the first cysteine-rich repeat of low density lipoprotein receptor impairs its transport but not lipoprotein binding in fibroblasts from a subject with familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7912-6. 3263645
  34. Leitersdorf E, Van der Westhuyzen DR, Coetzee GA, Hobbs HH: Two common low density lipoprotein receptor gene mutations cause familial hypercholesterolemia in Afrikaners. J Clin Invest. 1989 Sep;84(3):954-61. 2569482
  35. Davis CG, Lehrman MA, Russell DW, Anderson RG, Brown MS, Goldstein JL: The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors. Cell. 1986 Apr 11;45(1):15-24. 3955657
  36. Rubinsztein DC, Jialal I, Leitersdorf E, Coetzee GA, van der Westhuyzen DR: Identification of two new LDL-receptor mutations causing homozygous familial hypercholesterolemia in a South African of Indian origin. Biochim Biophys Acta. 1993 Aug 4;1182(1):75-82. 8347689
  37. Leitersdorf E, Tobin EJ, Davignon J, Hobbs HH: Common low-density lipoprotein receptor mutations in the French Canadian population. J Clin Invest. 1990 Apr;85(4):1014-23. 2318961
  38. Miyake Y, Tajima S, Funahashi T, Yamamura T, Yamamoto A: A point mutation of low-density-lipoprotein receptor causing rapid degradation of the receptor. Eur J Biochem. 1992 Nov 15;210(1):1-7. 1446662
  39. Meiner V, Landsberger D, Berkman N, Reshef A, Segal P, Seftel HC, van der Westhuyzen DR, Jeenah MS, Coetzee GA, Leitersdorf E: A common Lithuanian mutation causing familial hypercholesterolemia in Ashkenazi Jews. Am J Hum Genet. 1991 Aug;49(2):443-9. 1867200
  40. Leitersdorf E, Reshef A, Meiner V, Dann EJ, Beigel Y, van Roggen FG, van der Westhuyzen DR, Coetzee GA: A missense mutation in the low density lipoprotein receptor gene causes familial hypercholesterolemia in Sephardic Jews. Hum Genet. 1993 Mar;91(2):141-7. 8462973
  41. Lelli N, Garuti R, Pedrazzi P, Ghisellini M, Simone ML, Tiozzo R, Cattin L, Valenti M, Rolleri M, Bertolini S, et al.: A new missense mutation (Cys297-->Phe) of the low density lipoprotein receptor in Italian patients with familial hypercholesterolemia (FHTrieste). Hum Genet. 1994 May;93(5):538-40. 8168830
  42. Soutar AK, Knight BL, Patel DD: Identification of a point mutation in growth factor repeat C of the low density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia that affects ligand binding and intracellular movement of receptors. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4166-70. 2726768
  43. Rubinsztein DC, Coetzee GA, Marais AD, Leitersdorf E, Seftel HC, van der Westhuyzen DR: Identification and properties of the proline664-leucine mutant LDL receptor in South Africans of Indian origin. J Lipid Res. 1992 Nov;33(11):1647-55. 1464748
  44. Koivisto UM, Viikari JS, Kontula K: Molecular characterization of minor gene rearrangements in Finnish patients with heterozygous familial hypercholesterolemia: identification of two common missense mutations (Gly823-->Asp and Leu380-->His) and eight rare mutations of the LDL receptor gene. Am J Hum Genet. 1995 Oct;57(4):789-97. 7573037
  45. Maruyama T, Miyake Y, Tajima S, Harada-Shiba M, Yamamura T, Tsushima M, Kishino B, Horiguchi Y, Funahashi T, Matsuzawa Y, et al.: Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population. Arterioscler Thromb Vasc Biol. 1995 Oct;15(10):1713-8. 7583548
  46. Tricot-Guerber F, Saint-Jore B, Valenti K, Foulon T, Bost M, Hadjian AJ: Identification of a mutation, N543H, in exon 11 of the low-density lipoprotein receptor gene in a French family with familial hypercholesterolemia. Hum Mutat. 1995;6(1):87-8. 7550239
  47. Ekstrom U, Abrahamson M, Sveger T, Lombardi P, Nilsson-Ehle P: An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia. Hum Genet. 1995 Aug;96(2):147-50. 7635461
  48. Leren TP, Solberg K, Rodningen OK, Tonstad S, Ose L: Two novel point mutations in the EGF precursor homology domain of the LDL receptor gene causing familial hypercholesterolemia. Hum Genet. 1995 Aug;96(2):241-2. 7635482
  49. Giesel J, Holzem G, Oette K: Screening for mutations in exon 4 of the LDL receptor gene in a German population with severe hypercholesterolemia. Hum Genet. 1995 Sep;96(3):301-4. 7649546
  50. Pereira E, Ferreira R, Hermelin B, Thomas G, Bernard C, Bertrand V, Nassiff H, Mendez del Castillo D, Bereziat G, Benlian P: Recurrent and novel LDL receptor gene mutations causing heterozygous familial hypercholesterolemia in La Habana. Hum Genet. 1995 Sep;96(3):319-22. 7649549
  51. Gundersen KE, Solberg K, Rodningen OK, Tonstad S, Ose L, Berg K, Leren TP: Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia. Clin Genet. 1996 Feb;49(2):85-7. 8740918
  52. Sundvold H, Solberg K, Tonstad S, Rodningen OK, Ose L, Berg K, Leren TP: A common missense mutation (C210G) in the LDL receptor gene among Norwegian familial hypercholesterolemia subjects. Hum Mutat. 1996;7(1):70-1. 8664907
  53. Webb JC, Sun XM, McCarthy SN, Neuwirth C, Thompson GR, Knight BL, Soutar AK: Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom. J Lipid Res. 1996 Feb;37(2):368-81. 9026534
  54. Peeters AV, Van Gaal LF, du Plessis L, Lombardi MP, Havekes LM, Kotze MJ: Mutational and genetic origin of LDL receptor gene mutations detected in both Belgian and Dutch familial hypercholesterolemics. Hum Genet. 1997 Aug;100(2):266-70. 9254862
  55. Jensen HK, Jensen TG, Faergeman O, Jensen LG, Andresen BS, Corydon MJ, Andreasen PH, Hansen PS, Heath F, Bolund L, Gregersen N: Two mutations in the same low-density lipoprotein receptor allele act in synergy to reduce receptor function in heterozygous familial hypercholesterolemia. Hum Mutat. 1997;9(5):437-44. 9143924
  56. Day IN, Whittall RA, O'Dell SD, Haddad L, Bolla MK, Gudnason V, Humphries SE: Spectrum of LDL receptor gene mutations in heterozygous familial hypercholesterolemia. Hum Mutat. 1997;10(2):116-27. 9259195
  57. Leren TP, Tonstad S, Gundersen KE, Bakken KS, Rodningen OK, Sundvold H, Ose L, Berg K: Molecular genetics of familial hypercholesterolaemia in Norway. J Intern Med. 1997 Mar;241(3):185-94. 9104431
  58. Gorski B, Kubalska J, Naruszewicz M, Lubinski J: LDL-R and Apo-B-100 gene mutations in Polish familial hypercholesterolemias. Hum Genet. 1998 May;102(5):562-5. 9654205
  59. Couture P, Vohl MC, Gagne C, Gaudet D, Torres AL, Lupien PJ, Despres JP, Labrie F, Simard J, Moorjani S: Identification of three mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians. Hum Mutat. 1998;Suppl 1:S226-31. 9452094
  60. Thiart R, Loubser O, de Villiers JN, Marx MP, Zaire R, Raal FJ, Kotze MJ: Two novel and two known low-density lipoprotein receptor gene mutations in German patients with familial hypercholesterolemia. Hum Mutat. 1998;Suppl 1:S232-3. 9452095
  61. Mak YT, Zhang J, Chan YS, Mak TW, Tomlinson B, Masarei JR, Pang CP: Possible common mutations in the low density lipoprotein receptor gene in Chinese. Hum Mutat. 1998;Suppl 1:S310-3. 9452118
  62. Cenarro A, Jensen HK, Casao E, Civeira F, Gonzalez-Bonillo J, Rodriguez-Rey JC, Gregersen N, Pocovi M: Identification of recurrent and novel mutations in the LDL receptor gene in Spanish patients with familial hypercholesterolemia. Mutations in brief no. 135. Online. Hum Mutat. 1998;11(5):413. 10206683
  63. Motti C, Bertolini S, Rampa P, Trovatello G, Liberatoscioli L, Calandra S, Federici G, Cortese C: Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online. Hum Mutat. 1998;12(3):290. 10660340
  64. Hirayama T, Yamaki E, Hata A, Tsuji M, Hashimoto K, Yamamoto M, Emi M: Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene. J Hum Genet. 1998;43(4):250-4. 9852677
  65. Lee WK, Haddad L, Macleod MJ, Dorrance AM, Wilson DJ, Gaffney D, Dominiczak MH, Packard CJ, Day IN, Humphries SE, Dominiczak AF: Identification of a common low density lipoprotein receptor mutation (C163Y) in the west of Scotland. J Med Genet. 1998 Jul;35(7):573-8. 9678702
  66. Jensen HK, Jensen LG, Meinertz H, Hansen PS, Gregersen N, Faergeman O: Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia. Atherosclerosis. 1999 Oct;146(2):337-44. 10532689
  67. Ekstrom U, Abrahamson M, Floren CH, Tollig H, Wettrell G, Nilsson G, Sun XM, Soutar AK, Nilsson-Ehle P: An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F). Clin Genet. 1999 May;55(5):332-9. 10422803
  68. Ebhardt M, Schmidt H, Doerk T, Tietge U, Haas R, Manns MP, Schmidtke J, Stuhrmann M: Mutation analysis in 46 German families with familial hypercholesterolemia: identification of 8 new mutations. Mutations in brief no. 226. Online. Hum Mutat. 1999;13(3):257. 10090484
  69. Hattori H, Nagano M, Iwata F, Homma Y, Egashira T, Okada T: Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia. Mutation in brief no. 248. Online. Hum Mutat. 1999;14(1):87. 10447263
  70. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. 10391209
  71. Bertolini S, Cantafora A, Averna M, Cortese C, Motti C, Martini S, Pes G, Postiglione A, Stefanutti C, Blotta I, Pisciotta L, Rolleri M, Langheim S, Ghisellini M, Rabbone I, Calandra S: Clinical expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):E41-52. 10978268
  72. Miltiadous G, Elisaf M, Xenophontos S, Manoli P, Cariolou MA: Segregation of a novel LDLR gene mutation (I430T) with familial hypercholesterolaemia in a Greek pedigree. Hum Mutat. 2000 Sep;16(3):277. 10980548
  73. Thiart R, Scholtz CL, Vergotine J, Hoogendijk CF, de Villiers JN, Nissen H, Brusgaard K, Gaffney D, Hoffs MS, Vermaak WJ, Kotze MJ: Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia. J Med Genet. 2000 Jul;37(7):514-9. 10882754
  74. Takahashi M, Ikeda U, Takahashi S, Hattori H, Iwasaki T, Ishihara M, Egashira T, Honma S, Asano Y, Shimada K: A novel mutation in exon 2 of the low-density lipoprotein-receptor gene in a patient with homozygous familial hypercholesterolemia. Clin Genet. 2001 Apr;59(4):290-2. 11298688
  75. Nauck MS, Koster W, Dorfer K, Eckes J, Scharnagl H, Gierens H, Nissen H, Nauck MA, Wieland H, Marz W: Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia. Hum Mutat. 2001 Aug;18(2):165-6. 11462246
  76. Humphries SE, Whittall RA, Hubbart CS, Maplebeck S, Cooper JA, Soutar AK, Naoumova R, Thompson GR, Seed M, Durrington PN, Miller JP, Betteridge DJ, Neil HA: Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet. 2006 Dec;43(12):943-9. 17142622
  77. Widhalm K, Dirisamer A, Lindemayr A, Kostner G: Diagnosis of families with familial hypercholesterolaemia and/or Apo B-100 defect by means of DNA analysis of LDL-receptor gene mutations. J Inherit Metab Dis. 2007 Apr;30(2):239-47. Epub 2007 Mar 8. 17347910
  78. Alonso R, Defesche JC, Tejedor D, Castillo S, Stef M, Mata N, Gomez-Enterria P, Martinez-Faedo C, Forga L, Mata P: Genetic diagnosis of familial hypercholesterolemia using a DNA-array based platform. Clin Biochem. 2009 Jun;42(9):899-903. doi: 10.1016/j.clinbiochem.2009.01.017. Epub 2009 Feb 6. 19318025
  79. Abifadel M, Rabes JP, Jambart S, Halaby G, Gannage-Yared MH, Sarkis A, Beaino G, Varret M, Salem N, Corbani S, Aydenian H, Junien C, Munnich A, Boileau C: The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. Hum Mutat. 2009 Jul;30(7):E682-91. doi: 10.1002/humu.21002. 19319977
  80. Al-Khateeb A, Zahri MK, Mohamed MS, Sasongko TH, Ibrahim S, Yusof Z, Zilfalil BA: Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia. BMC Med Genet. 2011 Mar 19;12:40. doi: 10.1186/1471-2350-12-40. 21418584
  81. Walus-Miarka M, Sanak M, Idzior-Walus B, Miarka P, Witek P, Malecki MT, Czarnecka D: A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland. Mol Biol Rep. 2012 May;39(5):5181-6. doi: 10.1007/s11033-011-1314-0. Epub 2011 Dec 13. 22160468
  82. Santos PC, Morgan AC, Jannes CE, Turolla L, Krieger JE, Santos RD, Pereira AC: Presence and type of low density lipoprotein receptor (LDLR) mutation influences the lipid profile and response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia. Atherosclerosis. 2014 Mar;233(1):206-10. doi: 10.1016/j.atherosclerosis.2013.12.028. Epub 2014 Jan 4. 24529145
  83. Etxebarria A, Benito-Vicente A, Stef M, Ostolaza H, Palacios L, Martin C: Activity-associated effect of LDL receptor missense variants located in the cysteine-rich repeats. Atherosclerosis. 2015 Feb;238(2):304-12. doi: 10.1016/j.atherosclerosis.2014.12.026. Epub 2014 Dec 20. 25545329
  84. Etxebarria A, Benito-Vicente A, Palacios L, Stef M, Cenarro A, Civeira F, Ostolaza H, Martin C: Functional characterization and classification of frequent low-density lipoprotein receptor variants. Hum Mutat. 2015 Jan;36(1):129-41. doi: 10.1002/humu.22721. Epub 2014 Nov 27. 25378237