GenomeNet

Database: UniProt
Entry: O75197
LinkDB: O75197
Original site: O75197 
ID   LRP5_HUMAN              Reviewed;        1615 AA.
AC   O75197; Q96TD6; Q9UES7; Q9UP66;
DT   10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2005, sequence version 2.
DT   13-FEB-2019, entry version 188.
DE   RecName: Full=Low-density lipoprotein receptor-related protein 5 {ECO:0000303|PubMed:24706814};
DE            Short=LRP-5 {ECO:0000303|PubMed:11336703};
DE   AltName: Full=Low-density lipoprotein receptor-related protein 7 {ECO:0000250|UniProtKB:Q91VN0};
DE            Short=LRP-7;
DE   Flags: Precursor;
GN   Name=LRP5 {ECO:0000303|PubMed:24706814, ECO:0000312|HGNC:HGNC:6697};
GN   Synonyms=LR3 {ECO:0000303|PubMed:9790987},
GN   LRP7 {ECO:0000250|UniProtKB:Q91VN0};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Osteoblast;
RX   PubMed=9790987; DOI=10.1006/bbrc.1998.9545;
RA   Dong Y., Lathrop W., Weaver D., Qiu Q., Cini J., Bertolini D.,
RA   Chen D.;
RT   "Molecular cloning and characterization of LR3, a novel LDL receptor
RT   family protein with mitogenic activity.";
RL   Biochem. Biophys. Res. Commun. 251:784-790(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-1525.
RC   TISSUE=Osteoblast;
RX   PubMed=9714764; DOI=10.1016/S0378-1119(98)00311-4;
RA   Hey P.J., Twells R.C.J., Phillips M.S., Nakagawa Y., Brown S.D.,
RA   Kawaguchi Y., Cox R., Xie G., Dugan V., Hammond H., Metzker M.L.,
RA   Todd J.A., Hess J.F.;
RT   "Cloning of a novel member of the low-density lipoprotein receptor
RT   family.";
RL   Gene 216:103-111(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11401438; DOI=10.1006/geno.2000.6492;
RA   Twells R.C.J., Metzker M.L., Brown S.D., Cox R., Garey C., Hammond H.,
RA   Hey P.J., Levy E., Nakagawa Y., Philips M.S., Todd J.A., Hess J.F.;
RT   "The sequence and gene characterization of a 400-kb candidate region
RT   for IDDM4 on chromosome 11q13.";
RL   Genomics 72:231-242(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-1330.
RX   PubMed=12509515; DOI=10.1073/pnas.0133792100;
RA   Fujino T., Asaba H., Kang M.J., Ikeda Y., Sone H., Takada S.,
RA   Kim D.H., Ioka R.X., Ono M., Tomoyori H., Okubo M., Murase T.,
RA   Kamataki A., Yamamoto J., Magoori K., Takahashi S., Miyamoto Y.,
RA   Oishi H., Nose M., Okazaki M., Usui S., Imaizumi K., Yanagisawa M.,
RA   Sakai J., Yamamoto T.T.;
RT   "Low-density lipoprotein receptor-related protein 5 (LRP5) is
RT   essential for normal cholesterol metabolism and glucose-induced
RT   insulin secretion.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:229-234(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   INTERACTION WITH MESD.
RX   PubMed=17488095; DOI=10.1021/bi700049g;
RA   Koduri V., Blacklow S.C.;
RT   "Requirement for natively unstructured regions of mesoderm development
RT   candidate 2 in promoting low-density lipoprotein receptor-related
RT   protein 6 maturation.";
RL   Biochemistry 46:6570-6577(2007).
RN   [9]
RP   INTERACTION WITH FZD8 IN WNT-FZD8-LRP5 COMPLEX, INTERACTION WITH DKK1,
RP   AND FUNCTION.
RX   PubMed=11448771; DOI=10.1016/S0960-9822(01)00290-1;
RA   Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X.;
RT   "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6.";
RL   Curr. Biol. 11:951-961(2001).
RN   [10]
RP   INTERACTION WITH DKK1 AND SOST, AND FUNCTION.
RX   PubMed=15778503; DOI=10.1074/jbc.M413274200;
RA   Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E.,
RA   Wu D.;
RT   "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling.";
RL   J. Biol. Chem. 280:19883-19887(2005).
RN   [11]
RP   INTERACTION WITH WNT1 IN THE WNT-FZD-LRP5 COMPLEX, INTERACTION WITH
RP   SOST, AND FUNCTION.
RX   PubMed=15908424; DOI=10.1074/jbc.M504308200;
RA   Semenov M., Tamai K., He X.;
RT   "SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.";
RL   J. Biol. Chem. 280:26770-26775(2005).
RN   [12]
RP   INTERACTION WITH CSNK1E.
RX   PubMed=16513652; DOI=10.1074/jbc.M510580200;
RA   Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S.,
RA   Hunt D.F., Virshup D.M.;
RT   "Negative regulation of LRP6 function by casein kinase I epsilon
RT   phosphorylation.";
RL   J. Biol. Chem. 281:12233-12241(2006).
RN   [13]
RP   INTERACTION WITH DKK1 AND MESD, AND CHARACTERIZATION OF VARIANT
RP   VAL-171.
RX   PubMed=19746449; DOI=10.1002/jcb.22335;
RA   Murrills R.J., Matteo J.J., Bhat B.M., Coleburn V.E., Allen K.M.,
RA   Chen W., Damagnez V., Bhat R.A., Bex F.J., Bodine P.V.;
RT   "A cell-based Dkk1 binding assay reveals roles for extracellular
RT   domains of LRP5 in Dkk1 interaction and highlights differences between
RT   wild-type and the high bone mass mutant LRP5(G171V).";
RL   J. Cell. Biochem. 108:1066-1075(2009).
RN   [14]
RP   INTERACTION WITH CAPRIN2.
RX   PubMed=18762581; DOI=10.1083/jcb.200803147;
RA   Ding Y., Xi Y., Chen T., Wang J.Y., Tao D.L., Wu Z.L., Li Y.P., Li C.,
RA   Zeng R., Li L.;
RT   "Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6
RT   phosphorylation.";
RL   J. Cell Biol. 182:865-872(2008).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [16]
RP   FUNCTION, AND INTERACTION WITH AXIN1.
RX   PubMed=11336703; DOI=10.1016/S1097-2765(01)00224-6;
RA   Mao J., Wang J., Liu B., Pan W., Farr G.H. III, Flynn C., Yuan H.,
RA   Takada S., Kimelman D., Li L., Wu D.;
RT   "Low-density lipoprotein receptor-related protein-5 binds to Axin and
RT   regulates the canonical Wnt signaling pathway.";
RL   Mol. Cell 7:801-809(2001).
RN   [17]
RP   FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH AXIN1.
RX   PubMed=14731402; DOI=10.1016/S1097-2765(03)00484-2;
RA   Tamai K., Zeng X., Liu C., Zhang X., Harada Y., Chang Z., He X.;
RT   "A mechanism for Wnt coreceptor activation.";
RL   Mol. Cell 13:149-156(2004).
RN   [18]
RP   INTERACTION WITH MESD, AND CHARACTERIZATION OF VARIANT HBM VAL-171.
RX   PubMed=15143163; DOI=10.1128/MCB.24.11.4677-4684.2004;
RA   Zhang Y., Wang Y., Li X., Zhang J., Mao J., Li Z., Zheng J., Li L.,
RA   Harris S., Wu D.;
RT   "The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with
RT   Mesd.";
RL   Mol. Cell. Biol. 24:4677-4684(2004).
RN   [19]
RP   INTERACTION WITH APCDD1.
RX   PubMed=20393562; DOI=10.1038/nature08875;
RA   Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A.,
RA   Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A.,
RA   Christiano A.M.;
RT   "APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis
RT   simplex.";
RL   Nature 464:1043-1047(2010).
RN   [20]
RP   VARIANT HBM VAL-171, AND POLYMORPHISM.
RX   PubMed=11741193; DOI=10.1086/338450;
RA   Little R.D., Carulli J.P., Del Mastro R.G., Dupuis J., Osborne M.,
RA   Folz C., Manning S.P., Swain P.M., Zhao S.-C., Eustace B., Lappe M.M.,
RA   Spitzer L., Zweier S., Braunschweiger K., Benchekroun Y., Hu X.,
RA   Adair R., Chee L., FitzGerald M.G., Tulig C., Caruso A., Tzellas N.,
RA   Bawa A., Franklin B., McGuire S., Nogues X., Gong G., Allen K.M.,
RA   Anisowicz A., Morales A.J., Lomedico P.T., Recker S.M.,
RA   Van Eerdewegh P., Recker R.R., Johnson M.L.;
RT   "A mutation in the LDL receptor-related protein 5 gene results in the
RT   autosomal dominant high-bone-mass trait.";
RL   Am. J. Hum. Genet. 70:11-19(2002).
RN   [21]
RP   VARIANTS OPTA1 TYR-111; ARG-171; THR-242 AND ILE-253, VARIANTS WENHY
RP   THR-214; VAL-214 AND THR-242, VARIANT VBCH2 THR-242, AND VARIANTS
RP   18-LEU--LEU-20 DEL; LEU-20 INS; ARG-89; MET-667 AND VAL-1330.
RX   PubMed=12579474; DOI=10.1086/368277;
RA   Van Wesenbeeck L., Cleiren E., Gram J., Beals R.K., Benichou O.,
RA   Scopelliti D., Key L., Renton T., Bartels C., Gong Y., Warman M.L.,
RA   de Vernejoul M.-C., Bollerslev J., Van Hul W.;
RT   "Six novel missense mutations in the LDL receptor-related protein 5
RT   (LRP5) gene in different conditions with an increased bone density.";
RL   Am. J. Hum. Genet. 72:763-771(2003).
RN   [22]
RP   VARIANTS EVR4 MET-173; HIS-1168 AND GLY-1361, AND VARIANT VAL-1525.
RX   PubMed=15024691; DOI=10.1086/383202;
RA   Toomes C., Bottomley H.M., Jackson R.M., Towns K.V., Scott S.,
RA   Mackey D.A., Craig J.E., Jiang L., Yang Z., Trembath R., Woodruff G.,
RA   Gregory-Evans C.Y., Gregory-Evans K., Parker M.J., Black G.C.M.,
RA   Downey L.M., Zhang K., Inglehearn C.F.;
RT   "Mutations in LRP5 or FZD4 underlie the common familial exudative
RT   vitreoretinopathy locus on chromosome 11q.";
RL   Am. J. Hum. Genet. 74:721-730(2004).
RN   [23]
RP   VARIANTS MET-667 AND VAL-1330.
RX   PubMed=15077203; DOI=10.1086/420771;
RA   Ferrari S.L., Deutsch S., Choudhury U., Chevalley T., Bonjour J.-P.,
RA   Dermitzakis E.T., Rizzoli R., Antonarakis S.E.;
RT   "Polymorphisms in the low-density lipoprotein receptor-related protein
RT   5 (LRP5) gene are associated with variation in vertebral bone mass,
RT   vertebral bone size, and stature in whites.";
RL   Am. J. Hum. Genet. 74:866-875(2004).
RN   [24]
RP   VARIANTS EVR4 GLN-570; GLY-752 AND LYS-1367.
RX   PubMed=15346351; DOI=10.1086/425080;
RA   Jiao X., Ventruto V., Trese M.T., Shastry B.S., Hejtmancik J.F.;
RT   "Autosomal recessive familial exudative vitreoretinopathy is
RT   associated with mutations in LRP5.";
RL   Am. J. Hum. Genet. 75:878-884(2004).
RN   [25]
RP   VARIANTS OPPG ASN-203; MET-244; PHE-307; TRP-348; GLN-353; LEU-356;
RP   LYS-390; GLU-400; ARG-404; ASN-434; LYS-460; GLN-494; VAL-520;
RP   TRP-570; ARG-610; ASN-683; HIS-733; TYR-1099; CYS-1113 AND ASP-1401,
RP   CHARACTERIZATION OF VARIANTS OPPG MET-244; LEU-356; LYS-390; ARG-404;
RP   ASN-434; VAL-520 AND ARG-610, CHARACTERIZATION OF VARIANTS EVR4
RP   MET-173; GLN-570; HIS-1168; GLY-1361 AND LYS-1367, AND FUNCTION.
RX   PubMed=16252235; DOI=10.1086/497706;
RG   Osteoporosis-Pseudoglioma collaborative group;
RA   Ai M., Heeger S., Bartels C.F., Schelling D.K.;
RT   "Clinical and molecular findings in osteoporosis-pseudoglioma
RT   syndrome.";
RL   Am. J. Hum. Genet. 77:741-753(2005).
RN   [26]
RP   VARIANTS OPPG ARG-478 AND CYS-504.
RX   PubMed=16679074; DOI=10.1016/j.bone.2006.02.069;
RA   Cheung W.M.W., Jin L.Y., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L.,
RA   Kung A.W.C.;
RT   "A family with osteoporosis pseudoglioma syndrome due to compound
RT   heterozygosity of two novel mutations in the LRP5 gene.";
RL   Bone 39:470-476(2006).
RN   [27]
RP   VARIANT OPPG ALA-409.
RX   PubMed=18602879; DOI=10.1016/j.bone.2008.04.020;
RA   Streeten E.A., McBride D., Puffenberger E., Hoffman M.E., Pollin T.I.,
RA   Donnelly P., Sack P., Morton H.;
RT   "Osteoporosis-pseudoglioma syndrome: description of 9 new cases and
RT   beneficial response to bisphosphonates.";
RL   Bone 43:584-590(2008).
RN   [28]
RP   VARIANT EVR4 ARG-550.
RX   PubMed=16929062; DOI=10.1136/bjo.2006.092114;
RA   Downey L.M., Bottomley H.M., Sheridan E., Ahmed M., Gilmour D.F.,
RA   Inglehearn C.F., Reddy A., Agrawal A., Bradbury J., Toomes C.;
RT   "Reduced bone mineral density and hyaloid vasculature remnants in a
RT   consanguineous recessive FEVR family with a mutation in LRP5.";
RL   Br. J. Ophthalmol. 90:1163-1167(2006).
RN   [29]
RP   VARIANTS OPPG GLN-494 AND TRP-570, VARIANT MET-667, AND FUNCTION.
RX   PubMed=11719191; DOI=10.1016/S0092-8674(01)00571-2;
RA   Gong Y., Slee R.B., Fukai N., Rawadi G., Roman-Roman S.,
RA   Reginato A.M., Wang H., Cundy T., Glorieux F.H., Lev D., Zacharin M.,
RA   Oexle K., Marcelino J., Suwairi W., Heeger S., Sabatakos G., Apte S.,
RA   Adkins W.N., Allgrove J., Arslan-Kirchner M., Batch J.A., Beighton P.,
RA   Black G.C., Boles R.G., Boon L.M., Borrone C., Brunner H.G.,
RA   Carle G.F., Dallapiccola B., De Paepe A., Floege B., Halfhide M.L.,
RA   Hall B., Hennekam R.C.M., Hirose T., Jans A., Jueppner H., Kim C.A.,
RA   Keppler-Noreuil K., Kohlschuetter A., LaCombe D., Lambert M.,
RA   Lemyre E., Letteboer T., Peltonen L., Ramesar R.S., Romanengo M.,
RA   Somer H., Steichen-Gersdorf E., Steinmann B., Sullivan B.,
RA   Superti-Furga A., Swoboda W., van den Boogaard M.-J., Van Hul W.,
RA   Vikkula M., Votruba M., Zabel B., Garcia T., Baron R., Olsen B.R.,
RA   Warman M.L.;
RT   "LDL receptor-related protein 5 (LRP5) affects bone accrual and eye
RT   development.";
RL   Cell 107:513-523(2001).
RN   [30]
RP   VARIANTS CYS-560; GLN-1036; CYS-1135 AND HIS-1156, CHARACTERIZATION OF
RP   VARIANTS CYS-560; GLN-1036; CYS-1135 AND HIS-1156, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=25920554; DOI=10.1038/ejhg.2015.86;
RA   Cnossen W.R., te Morsche R.H., Hoischen A., Gilissen C., Venselaar H.,
RA   Mehdi S., Bergmann C., Losekoot M., Breuning M.H., Peters D.J.,
RA   Veltman J.A., Drenth J.P.;
RT   "LRP5 variants may contribute to ADPKD.";
RL   Eur. J. Hum. Genet. 24:237-242(2016).
RN   [31]
RP   VARIANTS EVR1 TRP-348; ASN-381; TRP-624 AND CYS-1517, CHARACTERIZATION
RP   OF VARIANTS EVR1 TRP-348; ASN-381; TRP-624 AND CYS-1517, AND FUNCTION.
RX   PubMed=27228167; DOI=10.1089/gtmb.2015.0322;
RA   Zhang L., Yang Y., Li S., Tai Z., Huang L., Liu Y., Zhu X., Di Y.,
RA   Qu C., Jiang Z., Li Y., Zhang G., Kim R., Sundaresan P., Yang Z.,
RA   Zhu X.;
RT   "Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in
RT   Indian Families with Familial Exudative Vitreoretinopathy.";
RL   Genet. Test. Mol. Biomarkers 20:346-351(2016).
RN   [32]
RP   VARIANTS EVR4 PHE-145; CYS-444; THR-522; MET-535; ARG-610; CYS-617;
RP   ALA-798 AND ASP-1121, AND VARIANTS VAL-97 AND MET-1540.
RX   PubMed=15981244; DOI=10.1002/humu.20191;
RA   Qin M., Hayashi H., Oshima K., Tahira T., Hayashi K., Kondo H.;
RT   "Complexity of the genotype-phenotype correlation in familial
RT   exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4
RT   genes.";
RL   Hum. Mutat. 26:104-112(2005).
RN   [33]
RP   VARIANT 15-LEU--LEU-20 DEL.
RX   PubMed=19177549; DOI=10.1002/humu.20916;
RA   Chung B.D., Kayserili H., Ai M., Freudenberg J., Uzumcu A.,
RA   Uyguner O., Bartels C.F., Honing S., Ramirez A., Hanisch F.G.,
RA   Nurnberg G., Nurnberg P., Warman M.L., Wollnik B., Kubisch C.,
RA   Netzer C.;
RT   "A mutation in the signal sequence of LRP5 in a family with an
RT   osteoporosis-pseudoglioma syndrome (OPPG)-like phenotype indicates a
RT   novel disease mechanism for trinucleotide repeats.";
RL   Hum. Mutat. 30:641-648(2009).
RN   [34]
RP   VARIANTS EVR4 LYS-441 AND PHE-1253.
RX   PubMed=20340138; DOI=10.1002/humu.21250;
RA   Nikopoulos K., Venselaar H., Collin R.W.J., Riveiro-Alvarez R.,
RA   Boonstra F.N., Hooymans J.M., Mukhopadhyay A., Shears D., van Bers M.,
RA   de Wijs I.J., van Essen A.J., Sijmons R.H., Tilanus M.A.D.,
RA   van Nouhuys C.E., Ayuso C., Hoefsloot L.H., Cremers F.P.M.;
RT   "Overview of the mutation spectrum in familial exudative
RT   vitreoretinopathy and Norrie disease with identification of 21 novel
RT   variants in FZD4, LRP5, and NDP.";
RL   Hum. Mutat. 31:656-666(2010).
RN   [35]
RP   VARIANTS EVR4 ALA-511 AND TRP-805.
RX   PubMed=19324841; DOI=10.1167/iovs.08-3320;
RA   Boonstra F.N., van Nouhuys C.E., Schuil J., de Wijs I.J.,
RA   van der Donk K.P., Nikopoulos K., Mukhopadhyay A., Scheffer H.,
RA   Tilanus M.A.D., Cremers F.P.M., Hoefsloot L.H.;
RT   "Clinical and molecular evaluation of probands and family members with
RT   familial exudative vitreoretinopathy.";
RL   Invest. Ophthalmol. Vis. Sci. 50:4379-4385(2009).
RN   [36]
RP   VARIANTS PRIMARY OSTEOPOROSIS THR-29 AND GLN-1036.
RX   PubMed=15824851; DOI=10.1359/JBMR.050101;
RA   Hartikka H., Makitie O., Mannikko M., Doria A.S., Daneman A.,
RA   Cole W.G., Ala-Kokko L., Sochett E.B.;
RT   "Heterozygous mutations in the LDL receptor-related protein 5 (LRP5)
RT   gene are associated with primary osteoporosis in children.";
RL   J. Bone Miner. Res. 20:783-789(2005).
RN   [37]
RP   VARIANT HBM MET-154.
RX   PubMed=15824861; DOI=10.1359/JBMR.041223;
RA   Rickels M.R., Zhang X., Mumm S., Whyte M.P.;
RT   "Oropharyngeal skeletal disease accompanying high bone mass and novel
RT   LRP5 mutation.";
RL   J. Bone Miner. Res. 20:878-885(2005).
RN   [38]
RP   VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455, VARIANT
RP   THR-1537, CHARACTERIZATION OF VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356
RP   AND LEU-455, AND CHARACTERIZATION OF VARIANT THR-1537.
RX   PubMed=16234968; DOI=10.1359/JBMR.050705;
RA   Crabbe P., Balemans W., Willaert A., van Pottelbergh I., Cleiren E.,
RA   Coucke P.J., Ai M., Goemaere S., van Hul W., de Paepe A.,
RA   Kaufman J.-M.;
RT   "Missense mutations in LRP5 are not a common cause of idiopathic
RT   osteoporosis in adult men.";
RL   J. Bone Miner. Res. 20:1951-1959(2005).
RN   [39]
RP   VARIANT HBM VAL-282, AND CHARACTERIZATION OF VARIANT HBM VAL-282.
RX   PubMed=17295608; DOI=10.1359/jbmr.070211;
RA   Balemans W., Devogelaer J.P., Cleiren E., Piters E., Caussin E.,
RA   Van Hul W.;
RT   "Novel LRP5 missense mutation in a patient with a high bone mass
RT   phenotype results in decreased DKK1-mediated inhibition of Wnt
RT   signaling.";
RL   J. Bone Miner. Res. 22:708-716(2007).
RN   [40]
RP   VARIANTS ARG-89 AND VAL-1330, AND INVOLVEMENT IN OSTEOPOROSIS.
RX   PubMed=14727154; DOI=10.1007/s10038-003-0111-6;
RA   Mizuguchi T., Furuta I., Watanabe Y., Tsukamoto K., Tomita H.,
RA   Tsujihata M., Ohta T., Kishino T., Matsumoto N., Minakami H.,
RA   Niikawa N., Yoshiura K.;
RT   "LRP5, low-density-lipoprotein-receptor-related protein 5, is a
RT   determinant for bone mineral density.";
RL   J. Hum. Genet. 49:80-86(2004).
RN   [41]
RP   VARIANT PRO-816, VARIANTS EVR4 THR-422; PRO-540 AND MET-852,
RP   CHARACTERIZATION OF VARIANTS EVR4 THR-422; PRO-540 AND MET-852, AND
RP   CHARACTERIZATION OF VARIANT PRO-816.
RX   PubMed=24715757;
RA   Fei P., Zhang Q., Huang L., Xu Y., Zhu X., Tai Z., Gong B., Ma S.,
RA   Yao Q., Li J., Zhao P., Yang Z.;
RT   "Identification of two novel LRP5 mutations in families with familial
RT   exudative vitreoretinopathy.";
RL   Mol. Vis. 20:395-409(2014).
RN   [42]
RP   VARIANT HBM VAL-171, AND CHARACTERIZATION OF VARIANT HBM VAL-171.
RX   PubMed=12015390; DOI=10.1056/NEJMoa013444;
RA   Boyden L.M., Mao J., Belsky J., Mitzner L., Farhi A., Mitnick M.A.,
RA   Wu D., Insogna K., Lifton R.P.;
RT   "High bone density due to a mutation in LDL-receptor-related protein
RT   5.";
RL   N. Engl. J. Med. 346:1513-1521(2002).
RN   [43]
RP   VARIANT OPPG ILE-531.
RX   PubMed=17437160; DOI=10.1007/s00198-007-0360-x;
RA   Barros E.R., Dias da Silva M.R., Kunii I.S., Hauache O.M.,
RA   Lazaretti-Castro M.;
RT   "A novel mutation in the LRP5 gene is associated with osteoporosis-
RT   pseudoglioma syndrome.";
RL   Osteoporos. Int. 18:1017-1018(2007).
RN   [44]
RP   INVOLVEMENT IN PCLD4, VARIANTS PCLD4 MET-454; TRP-1188; SER-1529 AND
RP   ASN-1551, CHARACTERIZATION OF VARIANTS PCLD4 MET-454; TRP-1188;
RP   SER-1529 AND ASN-1551, AND FUNCTION.
RX   PubMed=24706814; DOI=10.1073/pnas.1309438111;
RA   Cnossen W.R., te Morsche R.H., Hoischen A., Gilissen C., Chrispijn M.,
RA   Venselaar H., Mehdi S., Bergmann C., Veltman J.A., Drenth J.P.;
RT   "Whole-exome sequencing reveals LRP5 mutations and canonical Wnt
RT   signaling associated with hepatic cystogenesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:5343-5348(2014).
RN   [45]
RP   INVOLVEMENT IN PCLD4, AND VARIANTS PCLD4 GLU-638; ALA-684; CYS-925 AND
RP   MET-1541.
RX   PubMed=28375157; DOI=10.1172/JCI90129;
RA   Besse W., Dong K., Choi J., Punia S., Fedeles S.V., Choi M.,
RA   Gallagher A.R., Huang E.B., Gulati A., Knight J., Mane S.,
RA   Tahvanainen E., Tahvanainen P., Sanna-Cherchi S., Lifton R.P.,
RA   Watnick T., Pei Y.P., Torres V.E., Somlo S.;
RT   "Isolated polycystic liver disease genes define effectors of
RT   polycystin-1 function.";
RL   J. Clin. Invest. 127:1772-1785(2017).
CC   -!- FUNCTION: Acts as a coreceptor with members of the frizzled family
CC       of seven-transmembrane spanning receptors to transduce signal by
CC       Wnt proteins (PubMed:11336703, PubMed:11448771, PubMed:15778503,
CC       PubMed:11719191, PubMed:15908424, PubMed:16252235). Activates the
CC       canonical Wnt signaling pathway that controls cell fate
CC       determination and self-renewal during embryonic development and
CC       adult tissue regeneration (PubMed:11336703, PubMed:11719191). In
CC       particular, may play an important role in the development of the
CC       posterior patterning of the epiblast during gastrulation (By
CC       similarity). During bone development, regulates osteoblast
CC       proliferation and differentiation thus determining bone mass
CC       (PubMed:11719191). Mechanistically, the formation of the signaling
CC       complex between Wnt ligand, frizzled receptor and LRP5 coreceptor
CC       promotes the recruitment of AXIN1 to LRP5, stabilizing beta-
CC       catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional
CC       programs (PubMed:11336703, PubMed:25920554, PubMed:24706814,
CC       PubMed:14731402). Acts as a coreceptor for non-Wnt proteins, such
CC       as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5
CC       receptor complex triggers beta-catenin/CTNNB1-dependent signaling
CC       known to be required for retinal vascular development
CC       (PubMed:27228167, PubMed:16252235). Plays a role in controlling
CC       postnatal vascular regression in retina via macrophage-induced
CC       endothelial cell apoptosis (By similarity).
CC       {ECO:0000250|UniProtKB:Q91VN0, ECO:0000269|PubMed:11336703,
CC       ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:11719191,
CC       ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15778503,
CC       ECO:0000269|PubMed:15908424, ECO:0000269|PubMed:16252235,
CC       ECO:0000269|PubMed:24706814, ECO:0000269|PubMed:25920554,
CC       ECO:0000269|PubMed:27228167}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated
CC       oligomer aggregates on Wnt-signaling (By similarity). Component of
CC       a Wnt-signaling complex that contains a WNT protein, a FZD protein
CC       and LRP5 or LRP6. Interacts with FZD8; the interaction is formed
CC       on WNT-binding and signaling (PubMed:11448771). Interacts (via the
CC       phosphorylated PPPSP motif domains) with AXIN1; the interaction
CC       prevents inhibition of beta-catenin phosphorylation and signaling
CC       and is enhanced in the presence of GSK3B and WNT1 or WNT3A
CC       (PubMed:11336703, PubMed:14731402). Interacts (via beta-propeller
CC       regions 3 and 4) with DKK1; the interaction, enhanced by MESD
CC       and/or KREMEN, inhibits beta-catenin signaling by preventing GSK3-
CC       mediated phosphorylation of the PPPSP motifs and subsequent, AXIN1
CC       binding (PubMed:11448771, PubMed:15778503, PubMed:19746449).
CC       Interacts with MESD; the interaction prevents the formation of
CC       LRP5 aggregates, targets LRP5 to the plasma membrane and, when
CC       complexed with KREMEN2, increases DKK1 binding (PubMed:17488095,
CC       PubMed:19746449, PubMed:15143163). Interacts with CSNK1E
CC       (PubMed:16513652). Interacts with SOST; the interaction
CC       antagonizes canonical Wnt signaling (PubMed:15778503,
CC       PubMed:15908424). Interacts with APCDD1 (PubMed:20393562).
CC       Interacts with CAPRIN2 (PubMed:18762581).
CC       {ECO:0000250|UniProtKB:Q91VN0, ECO:0000269|PubMed:11336703,
CC       ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:14731402,
CC       ECO:0000269|PubMed:15143163, ECO:0000269|PubMed:15778503,
CC       ECO:0000269|PubMed:15908424, ECO:0000269|PubMed:16513652,
CC       ECO:0000269|PubMed:17488095, ECO:0000269|PubMed:18762581,
CC       ECO:0000269|PubMed:19746449, ECO:0000269|PubMed:20393562}.
CC   -!- INTERACTION:
CC       Q8J025:APCDD1; NbExp=3; IntAct=EBI-2466421, EBI-2683489;
CC       Q6IMN6:CAPRIN2; NbExp=3; IntAct=EBI-2466421, EBI-6918449;
CC       Q9BQB4:SOST; NbExp=2; IntAct=EBI-2466421, EBI-5746563;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q91VN0};
CC       Single-pass type I membrane protein
CC       {ECO:0000250|UniProtKB:Q91VN0}. Endoplasmic reticulum
CC       {ECO:0000269|PubMed:25920554}. Note=Chaperoned to the plasma
CC       membrane by MESD. {ECO:0000250|UniProtKB:Q91VN0}.
CC   -!- TISSUE SPECIFICITY: Widely expressed, with the highest level of
CC       expression in the liver and in aorta.
CC       {ECO:0000269|PubMed:9790987}.
CC   -!- PTM: Phosphorylation of cytoplasmic PPPSP motifs regulates the
CC       signal transduction of the Wnt signaling pathway through acting as
CC       a docking site for AXIN1.
CC   -!- POLYMORPHISM: Genetic variations in LRP5 define the bone mineral
CC       density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance
CC       in bone mineral density influences bone mass and contributes to
CC       size determination in the general population.
CC       {ECO:0000269|PubMed:11741193}.
CC   -!- DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: A
CC       disorder of the retinal vasculature characterized by an abrupt
CC       cessation of growth of peripheral capillaries, leading to an
CC       avascular peripheral retina. This may lead to compensatory retinal
CC       neovascularization, which is thought to be induced by hypoxia from
CC       the initial avascular insult. New vessels are prone to leakage and
CC       rupture causing exudates and bleeding, followed by scarring,
CC       retinal detachment and blindness. Clinical features can be highly
CC       variable, even within the same family. Patients with mild forms of
CC       the disease are asymptomatic, and their only disease related
CC       abnormality is an arc of avascular retina in the extreme temporal
CC       periphery. In many ways the disease resembles retinopathy of
CC       prematurity but there is no evidence of prematurity or small birth
CC       weight in the patient history. {ECO:0000269|PubMed:27228167}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A
CC       disorder of the retinal vasculature characterized by an abrupt
CC       cessation of growth of peripheral capillaries, leading to an
CC       avascular peripheral retina. This may lead to compensatory retinal
CC       neovascularization, which is thought to be induced by hypoxia from
CC       the initial avascular insult. New vessels are prone to leakage and
CC       rupture causing exudates and bleeding, followed by scarring,
CC       retinal detachment and blindness. Clinical features can be highly
CC       variable, even within the same family. Patients with mild forms of
CC       the disease are asymptomatic, and their only disease related
CC       abnormality is an arc of avascular retina in the extreme temporal
CC       periphery. {ECO:0000269|PubMed:15024691,
CC       ECO:0000269|PubMed:15346351, ECO:0000269|PubMed:15981244,
CC       ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16929062,
CC       ECO:0000269|PubMed:19324841, ECO:0000269|PubMed:20340138,
CC       ECO:0000269|PubMed:24715757}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal
CC       disorder characterized by decreased bone mass and deterioration of
CC       bone microarchitecture without alteration in the composition of
CC       bone. The result is fragile bones and an increased risk of
CC       fractures, even after minimal trauma. Osteoporosis is a chronic
CC       condition of multifactorial etiology and is usually clinically
CC       silent until a fracture occurs. {ECO:0000269|PubMed:14727154,
CC       ECO:0000269|PubMed:15824851, ECO:0000269|PubMed:16234968}.
CC       Note=Disease susceptibility is associated with variations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Osteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770]: A
CC       disease characterized by congenital or infancy-onset blindness and
CC       severe juvenile-onset osteoporosis and spontaneous fractures.
CC       Additional clinical manifestations may include microphthalmos,
CC       abnormalities of the iris, lens or vitreous, cataracts, short
CC       stature, microcephaly, ligamental laxity, mental retardation and
CC       hypotonia. {ECO:0000269|PubMed:11719191,
CC       ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16679074,
CC       ECO:0000269|PubMed:17437160, ECO:0000269|PubMed:18602879}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: High bone mass trait (HBM) [MIM:601884]: Rare phenotype
CC       characterized by exceptionally dense bones. HBM individuals show
CC       otherwise a completely normal skeletal structure and no other
CC       unusual clinical findings. {ECO:0000269|PubMed:11741193,
CC       ECO:0000269|PubMed:12015390, ECO:0000269|PubMed:15143163,
CC       ECO:0000269|PubMed:15824861, ECO:0000269|PubMed:17295608}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Endosteal hyperostosis, Worth type (WENHY) [MIM:144750]:
CC       An autosomal dominant sclerosing bone dysplasia clinically
CC       characterized by elongation of the mandible, increased gonial
CC       angle, flattened forehead, and the presence of a slowly enlarging
CC       osseous prominence of the hard palate (torus palatinus). Serum
CC       calcium, phosphorus and alkaline phosphatase levels are normal.
CC       Radiologically, it is characterized by early thickening of the
CC       endosteum of long bones, the skull and of the mandible. With
CC       advancing age, the trabeculae of the metaphysis become thickened.
CC       WENHY becomes clinically and radiologically evident by
CC       adolescence, does not cause deformity except in the skull and
CC       mandible, and is not associated with bone pain or fracture.
CC       Affected patients have normal height, proportion, intelligence and
CC       longevity. {ECO:0000269|PubMed:12579474}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Osteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634]:
CC       A rare genetic disease characterized by abnormally dense bone, due
CC       to defective resorption of immature bone. Osteopetrosis occurs in
CC       two forms: a severe autosomal recessive form occurring in utero,
CC       infancy, or childhood, and a benign autosomal dominant form
CC       occurring in adolescence or adulthood. OPTA1 is an autosomal
CC       dominant form characterized by generalized osteosclerosis most
CC       pronounced in the cranial vault. Patients are often asymptomatic,
CC       but some suffer from pain and hearing loss. It appears to be the
CC       only type of osteopetrosis not associated with an increased
CC       fracture rate. {ECO:0000269|PubMed:12579474}. Note=The disease is
CC       caused by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Van Buchem disease 2 (VBCH2) [MIM:607636]: VBCH2 is an
CC       autosomal dominant sclerosing bone dysplasia characterized by
CC       cranial osteosclerosis, thickened calvaria and cortices of long
CC       bones, enlarged mandible and normal serum alkaline phosphatase
CC       levels. {ECO:0000269|PubMed:12579474}. Note=The disease is caused
CC       by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Polycystic liver disease 4 with or without kidney cysts
CC       (PCLD4) [MIM:617875]: A form of polycystic liver disease, an
CC       autosomal dominant hepatobiliary disease characterized by
CC       overgrowth of biliary epithelium and supportive connective tissue,
CC       resulting in multiple liver cysts. PCLD4 patients may also develop
CC       kidney cysts that usually do not result in clinically significant
CC       renal disease. {ECO:0000269|PubMed:24706814,
CC       ECO:0000269|PubMed:28375157}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Note=LRP5 variations may act as a disease modifier in
CC       autosomal dominant polycystic kidney disease (ADPKD) in patients
CC       who have causative mutations in PKD1. May contribute to the
CC       disease phenotype heterogeneity and hepatic cystogenesis.
CC       {ECO:0000269|PubMed:25920554}.
CC   -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/LRP5ID44282ch11q13.html";
DR   EMBL; AF077820; AAC72791.1; -; mRNA.
DR   EMBL; AF064548; AAC36467.1; -; mRNA.
DR   EMBL; AF283321; AAK52433.1; -; Genomic_DNA.
DR   EMBL; AF283320; AAK52433.1; JOINED; Genomic_DNA.
DR   EMBL; AB017498; BAA33051.1; -; mRNA.
DR   EMBL; AP000807; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471076; EAW74705.1; -; Genomic_DNA.
DR   EMBL; BC150595; AAI50596.1; -; mRNA.
DR   CCDS; CCDS8181.1; -.
DR   PIR; JE0372; JE0372.
DR   RefSeq; NP_001278831.1; NM_001291902.1.
DR   RefSeq; NP_002326.2; NM_002335.3.
DR   UniGene; Hs.6347; -.
DR   ProteinModelPortal; O75197; -.
DR   SMR; O75197; -.
DR   BioGrid; 110220; 45.
DR   CORUM; O75197; -.
DR   DIP; DIP-47265N; -.
DR   ELM; O75197; -.
DR   IntAct; O75197; 10.
DR   MINT; O75197; -.
DR   STRING; 9606.ENSP00000294304; -.
DR   GlyConnect; 1468; -.
DR   iPTMnet; O75197; -.
DR   PhosphoSitePlus; O75197; -.
DR   BioMuta; LRP5; -.
DR   EPD; O75197; -.
DR   jPOST; O75197; -.
DR   PaxDb; O75197; -.
DR   PeptideAtlas; O75197; -.
DR   PRIDE; O75197; -.
DR   ProteomicsDB; 49865; -.
DR   Ensembl; ENST00000294304; ENSP00000294304; ENSG00000162337.
DR   GeneID; 4041; -.
DR   KEGG; hsa:4041; -.
DR   UCSC; uc001ont.4; human.
DR   CTD; 4041; -.
DR   DisGeNET; 4041; -.
DR   EuPathDB; HostDB:ENSG00000162337.11; -.
DR   GeneCards; LRP5; -.
DR   GeneReviews; LRP5; -.
DR   HGNC; HGNC:6697; LRP5.
DR   HPA; CAB013001; -.
DR   HPA; HPA030505; -.
DR   MalaCards; LRP5; -.
DR   MIM; 133780; phenotype.
DR   MIM; 144750; phenotype.
DR   MIM; 166710; phenotype.
DR   MIM; 259770; phenotype.
DR   MIM; 601813; phenotype.
DR   MIM; 601884; phenotype.
DR   MIM; 603506; gene.
DR   MIM; 607634; phenotype.
DR   MIM; 607636; phenotype.
DR   MIM; 617875; phenotype.
DR   neXtProt; NX_O75197; -.
DR   OpenTargets; ENSG00000162337; -.
DR   Orphanet; 2783; Autosomal dominant osteopetrosis type 1.
DR   Orphanet; 2790; Endosteal hyperostosis, Worth type.
DR   Orphanet; 891; Familial exudative vitreoretinopathy.
DR   Orphanet; 3416; Hyperostosis corticalis generalisata.
DR   Orphanet; 2924; Isolated polycystic liver disease.
DR   Orphanet; 498481; LRP5-related primary osteoporosis.
DR   Orphanet; 2788; Osteoporosis-pseudoglioma syndrome.
DR   Orphanet; 178377; Osteosclerosis-developmental delay-craniosynostosis syndrome.
DR   Orphanet; 90050; Retinopathy of prematurity.
DR   PharmGKB; PA30455; -.
DR   eggNOG; ENOG410IPT4; Eukaryota.
DR   eggNOG; ENOG410XSY5; LUCA.
DR   GeneTree; ENSGT00940000156574; -.
DR   HOGENOM; HOG000230697; -.
DR   HOVERGEN; HBG049167; -.
DR   InParanoid; O75197; -.
DR   KO; K03068; -.
DR   OMA; PFTGISC; -.
DR   OrthoDB; 1349932at2759; -.
DR   PhylomeDB; O75197; -.
DR   TreeFam; TF315253; -.
DR   Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR   Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR   Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR   Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR   Reactome; R-HSA-5339717; Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
DR   Reactome; R-HSA-5340588; RNF mutants show enhanced WNT signaling and proliferation.
DR   SignaLink; O75197; -.
DR   SIGNOR; O75197; -.
DR   ChiTaRS; LRP5; human.
DR   GeneWiki; LRP5; -.
DR   GenomeRNAi; 4041; -.
DR   PRO; PR:O75197; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000162337; Expressed in 171 organ(s), highest expression level in right lobe of liver.
DR   ExpressionAtlas; O75197; baseline and differential.
DR   Genevisible; O75197; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0043235; C:receptor complex; IDA:BHF-UCL.
DR   GO; GO:1990909; C:Wnt signalosome; NAS:ParkinsonsUK-UCL.
DR   GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; TAS:ParkinsonsUK-UCL.
DR   GO; GO:1904928; F:coreceptor activity involved in canonical Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0071936; F:coreceptor activity involved in Wnt signaling pathway; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0042813; F:Wnt-activated receptor activity; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0017147; F:Wnt-protein binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0060612; P:adipose tissue development; IMP:BHF-UCL.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR   GO; GO:0048539; P:bone marrow development; IMP:BHF-UCL.
DR   GO; GO:0060349; P:bone morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0046849; P:bone remodeling; IBA:GO_Central.
DR   GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IBA:GO_Central.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR   GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR   GO; GO:0001702; P:gastrulation with mouth forming second; IBA:GO_Central.
DR   GO; GO:0006007; P:glucose catabolic process; IMP:BHF-UCL.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:BHF-UCL.
DR   GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:BHF-UCL.
DR   GO; GO:0002076; P:osteoblast development; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:BHF-UCL.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR   GO; GO:0008217; P:regulation of blood pressure; IMP:BHF-UCL.
DR   GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IBA:GO_Central.
DR   GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:BHF-UCL.
DR   GO; GO:0061304; P:retinal blood vessel morphogenesis; IMP:BHF-UCL.
DR   GO; GO:1901998; P:toxin transport; IEA:GOC.
DR   GO; GO:0016055; P:Wnt signaling pathway; IDA:BHF-UCL.
DR   CDD; cd00112; LDLa; 3.
DR   Gene3D; 2.120.10.30; -; 4.
DR   InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR   InterPro; IPR000742; EGF-like_dom.
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   InterPro; IPR017049; LRP5/6.
DR   Pfam; PF00057; Ldl_recept_a; 3.
DR   Pfam; PF00058; Ldl_recept_b; 13.
DR   PIRSF; PIRSF036314; LDL_recpt-rel_p5/6; 1.
DR   PRINTS; PR00261; LDLRECEPTOR.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00192; LDLa; 3.
DR   SMART; SM00135; LY; 20.
DR   SUPFAM; SSF57424; SSF57424; 3.
DR   PROSITE; PS01209; LDLRA_1; 3.
DR   PROSITE; PS50068; LDLRA_2; 3.
DR   PROSITE; PS51120; LDLRB; 20.
PE   1: Evidence at protein level;
KW   Complete proteome; Developmental protein; Disease mutation;
KW   Disulfide bond; EGF-like domain; Endocytosis; Endoplasmic reticulum;
KW   Glycoprotein; Membrane; Osteogenesis imperfecta; Osteopetrosis;
KW   Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat;
KW   Signal; Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT   SIGNAL        1     31       {ECO:0000255}.
FT   CHAIN        32   1615       Low-density lipoprotein receptor-related
FT                                protein 5.
FT                                /FTId=PRO_0000017328.
FT   TOPO_DOM     32   1384       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1385   1407       Helical. {ECO:0000255}.
FT   TOPO_DOM   1408   1615       Cytoplasmic. {ECO:0000255}.
FT   REPEAT       75    119       LDL-receptor class B 1.
FT   REPEAT       78     81       YWTD 1.
FT   REPEAT      120    162       LDL-receptor class B 2.
FT   REPEAT      123    126       YWTD 2.
FT   REPEAT      163    206       LDL-receptor class B 3.
FT   REPEAT      166    169       YWTD 3.
FT   REPEAT      207    247       LDL-receptor class B 4.
FT   REPEAT      248    290       LDL-receptor class B 5.
FT   REPEAT      251    254       YWTD 4.
FT   DOMAIN      295    337       EGF-like 1.
FT   REPEAT      385    427       LDL-receptor class B 6.
FT   REPEAT      388    391       YWTD 5.
FT   REPEAT      428    470       LDL-receptor class B 7.
FT   REPEAT      431    434       YWTD 6.
FT   REPEAT      471    514       LDL-receptor class B 8.
FT   REPEAT      474    477       YWTD 7.
FT   REPEAT      515    557       LDL-receptor class B 9.
FT   REPEAT      558    600       LDL-receptor class B 10.
FT   REPEAT      559    562       YWTD 8.
FT   DOMAIN      601    641       EGF-like 2.
FT   REPEAT      687    729       LDL-receptor class B 11.
FT   REPEAT      690    693       YWTD 9.
FT   REPEAT      730    772       LDL-receptor class B 12.
FT   REPEAT      773    815       LDL-receptor class B 13.
FT   REPEAT      816    855       LDL-receptor class B 14.
FT   REPEAT      819    822       YWTD 10.
FT   REPEAT      856    898       LDL-receptor class B 15.
FT   REPEAT      859    862       YWTD 11.
FT   DOMAIN      902    942       EGF-like 3.
FT   REPEAT      989   1035       LDL-receptor class B 16.
FT   REPEAT     1036   1078       LDL-receptor class B 17.
FT   REPEAT     1079   1123       LDL-receptor class B 18.
FT   REPEAT     1124   1164       LDL-receptor class B 19.
FT   REPEAT     1165   1207       LDL-receptor class B 20.
FT   DOMAIN     1213   1254       EGF-like 4.
FT   DOMAIN     1258   1296       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1297   1333       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1335   1371       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   REGION       32    288       Beta-propeller 1.
FT   REGION      341    602       Beta-propeller 2.
FT   REGION      644    903       Beta-propeller 3.
FT   REGION      945   1212       Beta-propeller 4.
FT   MOTIF      1500   1506       PPPSP motif A.
FT   MOTIF      1538   1545       PPPSP motif B.
FT   MOTIF      1574   1581       PPPSP motif C.
FT   MOTIF      1591   1596       PPPSP motif D.
FT   MOTIF      1605   1612       PPPSP motif E.
FT   COMPBIAS   1495   1610       Pro-rich.
FT   CARBOHYD     93     93       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    138    138       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    446    446       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    499    499       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    705    705       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    878    878       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    299    310       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    306    321       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    323    336       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    605    616       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    612    625       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    627    640       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    906    917       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    913    926       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    928    941       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1217   1228       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1224   1238       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1240   1253       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1259   1273       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1266   1286       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1280   1295       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1298   1310       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1305   1323       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1317   1332       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1336   1348       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1343   1361       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1355   1370       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   VARIANT      15     20       Missing (found in a family with
FT                                osteoporosis pseudoglioma syndrome;
FT                                impairs protein trafficking to the
FT                                endoplasmic reticulum and cell membrane).
FT                                {ECO:0000269|PubMed:19177549}.
FT                                /FTId=VAR_058582.
FT   VARIANT      18     20       Missing. {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021804.
FT   VARIANT      20     20       L -> LL. {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021805.
FT   VARIANT      29     29       A -> T (in primary osteoporosis).
FT                                {ECO:0000269|PubMed:15824851}.
FT                                /FTId=VAR_063941.
FT   VARIANT      89     89       Q -> R (in dbSNP:rs41494349).
FT                                {ECO:0000269|PubMed:12579474,
FT                                ECO:0000269|PubMed:14727154}.
FT                                /FTId=VAR_021806.
FT   VARIANT      97     97       A -> V (in dbSNP:rs143433231).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063942.
FT   VARIANT     111    111       D -> Y (in OPTA1).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021807.
FT   VARIANT     145    145       L -> F (in EVR4; dbSNP:rs80358305).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063943.
FT   VARIANT     154    154       R -> M (in HBM).
FT                                {ECO:0000269|PubMed:15824861}.
FT                                /FTId=VAR_063944.
FT   VARIANT     171    171       G -> R (in OPTA1; dbSNP:rs121908669).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021808.
FT   VARIANT     171    171       G -> V (in HBM; also in HBM individuals
FT                                with enlarged mandible and torus
FT                                palatinus; abolishes interaction with
FT                                MESD; impairs transport to cell surface;
FT                                no enhancement of DKK1 binding by MESD
FT                                resulting in impaired inhibition of Wnt
FT                                signaling by DKK1; dbSNP:rs121908668).
FT                                {ECO:0000269|PubMed:11741193,
FT                                ECO:0000269|PubMed:12015390,
FT                                ECO:0000269|PubMed:15143163,
FT                                ECO:0000269|PubMed:19746449}.
FT                                /FTId=VAR_021809.
FT   VARIANT     173    173       T -> M (in EVR4; an individual with
FT                                abnormal retinal vasculature and retinal
FT                                folds; dbSNP:rs80358306).
FT                                {ECO:0000269|PubMed:15024691,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_018465.
FT   VARIANT     203    203       D -> N (in OPPG; dbSNP:rs760548029).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063945.
FT   VARIANT     214    214       A -> T (in WENHY; dbSNP:rs121908671).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021810.
FT   VARIANT     214    214       A -> V (in WENHY; dbSNP:rs121908672).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021811.
FT   VARIANT     242    242       A -> T (in OPTA1, VBCH2 and WENHY;
FT                                dbSNP:rs121908670).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021812.
FT   VARIANT     244    244       T -> M (in OPPG; appears to traffic less
FT                                well than does the wild-type protein;
FT                                appears to be post-translationally
FT                                modified similar to wild-type protein; is
FT                                unable to transduce Wnt signal; has a
FT                                significantly reduced ability to
FT                                transduce Norrin signal;
FT                                dbSNP:rs397514665).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063946.
FT   VARIANT     253    253       T -> I (in OPTA1; dbSNP:rs121908673).
FT                                {ECO:0000269|PubMed:12579474}.
FT                                /FTId=VAR_021813.
FT   VARIANT     282    282       M -> V (in HBM; unknown pathological
FT                                significance; lowered LRP5-mediated Wnt
FT                                signaling; no effect on DKK1 binding).
FT                                {ECO:0000269|PubMed:17295608}.
FT                                /FTId=VAR_063412.
FT   VARIANT     307    307       S -> F (in OPPG; dbSNP:rs1219101402).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063947.
FT   VARIANT     348    348       R -> W (in OPPG and EVR1; reduces Norrin
FT                                signal transduction; dbSNP:rs1320065036).
FT                                {ECO:0000269|PubMed:16252235,
FT                                ECO:0000269|PubMed:27228167}.
FT                                /FTId=VAR_063948.
FT   VARIANT     353    353       R -> Q (in OPPG).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063949.
FT   VARIANT     356    356       S -> L (in idiopathic osteoporosis and
FT                                OPPG; appears to traffic comparably than
FT                                does the wild-type protein; appears to be
FT                                post-translationally modified similar to
FT                                wild-type protein; is unable to transduce
FT                                Wnt signal; has a significantly reduced
FT                                ability to transduce Norrin signal;
FT                                dbSNP:rs1158745675).
FT                                {ECO:0000269|PubMed:16234968,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063950.
FT   VARIANT     381    381       D -> N (in EVR1; reduces Norrin signal
FT                                transduction; dbSNP:rs1332274863).
FT                                {ECO:0000269|PubMed:27228167}.
FT                                /FTId=VAR_076548.
FT   VARIANT     390    390       T -> K (in OPPG; is unable to traffic
FT                                normally; appears to be post-
FT                                translationally modified similar to wild-
FT                                type protein; is unable to transduce Wnt
FT                                signal; has a significantly reduced
FT                                ability to transduce Norrin signal).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063951.
FT   VARIANT     400    400       A -> E (in OPPG; dbSNP:rs201320326).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063952.
FT   VARIANT     404    404       G -> R (in OPPG; appears to traffic less
FT                                well than does the wild-type protein;
FT                                appears to be post-translationally
FT                                modified similar to wild-type protein;
FT                                has 50% of wild-type activity to
FT                                transduce Wnt signal; has a significantly
FT                                reduced ability to transduce Norrin
FT                                signal; dbSNP:rs750791263).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063953.
FT   VARIANT     409    409       T -> A (in OPPG; dbSNP:rs1273567061).
FT                                {ECO:0000269|PubMed:18602879}.
FT                                /FTId=VAR_063954.
FT   VARIANT     422    422       A -> T (in EVR4; the mutation results in
FT                                significantly reduced Norrin signal
FT                                transduction; dbSNP:rs774342727).
FT                                {ECO:0000269|PubMed:24715757}.
FT                                /FTId=VAR_071012.
FT   VARIANT     434    434       D -> N (in OPPG; appears to traffic less
FT                                well than does the wild-type protein;
FT                                appears to be post-translationally
FT                                modified similar to wild-type protein;
FT                                has 50% of wild-type activity to
FT                                transduce Wnt signal; has a significantly
FT                                reduced ability to transduce Norrin
FT                                signal; dbSNP:rs757888034).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063955.
FT   VARIANT     441    441       E -> K (in EVR4; dbSNP:rs376152274).
FT                                {ECO:0000269|PubMed:20340138}.
FT                                /FTId=VAR_063956.
FT   VARIANT     444    444       R -> C (in EVR4; associated in a EVR1
FT                                patient with mutation GLN-417 in FZD4;
FT                                dbSNP:rs80358308).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063957.
FT   VARIANT     454    454       V -> M (in PCLD4; unknown pathological
FT                                significance; dbSNP:rs373910016).
FT                                {ECO:0000269|PubMed:24706814}.
FT                                /FTId=VAR_080857.
FT   VARIANT     455    455       S -> L (in idiopathic osteoporosis; shows
FT                                an inhibitory effect on Wnt signal
FT                                transduction; dbSNP:rs930355318).
FT                                {ECO:0000269|PubMed:16234968}.
FT                                /FTId=VAR_063958.
FT   VARIANT     460    460       E -> K (in OPPG; dbSNP:rs866606166).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063959.
FT   VARIANT     478    478       W -> R (in OPPG; dbSNP:rs1318906451).
FT                                {ECO:0000269|PubMed:16679074}.
FT                                /FTId=VAR_063960.
FT   VARIANT     494    494       R -> Q (in OPPG; dbSNP:rs121908664).
FT                                {ECO:0000269|PubMed:11719191,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_021814.
FT   VARIANT     504    504       W -> C (in OPPG; dbSNP:rs545508982).
FT                                {ECO:0000269|PubMed:16679074}.
FT                                /FTId=VAR_063961.
FT   VARIANT     511    511       D -> A (in EVR4; dbSNP:rs1245625202).
FT                                {ECO:0000269|PubMed:19324841}.
FT                                /FTId=VAR_063962.
FT   VARIANT     520    520       G -> V (in OPPG; appears to traffic
FT                                comparably than does the wild-type
FT                                protein; appears to be post-
FT                                translationally modified similar to wild-
FT                                type protein; is unable to transduce Wnt
FT                                signal; has a significantly reduced
FT                                ability to transduce Norrin signal).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063963.
FT   VARIANT     522    522       A -> T (in EVR4; dbSNP:rs80358309).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063964.
FT   VARIANT     531    531       N -> I (in OPPG).
FT                                {ECO:0000269|PubMed:17437160}.
FT                                /FTId=VAR_063965.
FT   VARIANT     535    535       T -> M (in EVR4; autosomal recessive;
FT                                dbSNP:rs80358310).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063966.
FT   VARIANT     540    540       L -> P (in EVR4; the mutation results in
FT                                significantly reduced Norrin signal
FT                                transduction).
FT                                {ECO:0000269|PubMed:24715757}.
FT                                /FTId=VAR_071013.
FT   VARIANT     550    550       G -> R (in EVR4; autosomal recessive;
FT                                dbSNP:rs80358311).
FT                                {ECO:0000269|PubMed:16929062}.
FT                                /FTId=VAR_063967.
FT   VARIANT     560    560       W -> C (found in a family affected by
FT                                polycystic kidney and liver disease;
FT                                unknown pathological significance; the
FT                                patients carried additional PKD1
FT                                variants; the mutation results in
FT                                significantly reduced WNT3A-induced
FT                                signaling pathway; dbSNP:rs377144001).
FT                                {ECO:0000269|PubMed:25920554}.
FT                                /FTId=VAR_080858.
FT   VARIANT     570    570       R -> Q (in EVR4; autosomal recessive; has
FT                                significantly reduced Wnt or Norrin
FT                                signal transduction; dbSNP:rs80358312).
FT                                {ECO:0000269|PubMed:15346351,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_021222.
FT   VARIANT     570    570       R -> W (in OPPG; dbSNP:rs121908665).
FT                                {ECO:0000269|PubMed:11719191,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_021815.
FT   VARIANT     610    610       G -> R (in EVR4 and OPPG; appears to
FT                                traffic less well than does the wild-type
FT                                protein; appears to be post-
FT                                translationally modified similar to wild-
FT                                type protein; has 60% of wild-type
FT                                activity to transduce Wnt signal; has a
FT                                significantly reduced ability to
FT                                transduce Norrin signal;
FT                                dbSNP:rs80358313).
FT                                {ECO:0000269|PubMed:15981244,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063968.
FT   VARIANT     617    617       F -> C (in EVR4; autosomal recessive;
FT                                dbSNP:rs80358314).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063969.
FT   VARIANT     624    624       R -> W (in EVR1; reduces Norrin signal
FT                                transduction; dbSNP:rs989864153).
FT                                {ECO:0000269|PubMed:27228167}.
FT                                /FTId=VAR_076549.
FT   VARIANT     638    638       K -> E (in PCLD4; unknown pathological
FT                                significance; the patient carried
FT                                additional PKHD1 variant;
FT                                dbSNP:rs758976409).
FT                                {ECO:0000269|PubMed:28375157}.
FT                                /FTId=VAR_080935.
FT   VARIANT     667    667       V -> M (in dbSNP:rs4988321).
FT                                {ECO:0000269|PubMed:11719191,
FT                                ECO:0000269|PubMed:12579474,
FT                                ECO:0000269|PubMed:15077203}.
FT                                /FTId=VAR_021816.
FT   VARIANT     683    683       D -> N (in OPPG; dbSNP:rs1470530779).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063970.
FT   VARIANT     684    684       V -> A (in PCLD4; unknown pathological
FT                                significance; the patient carried
FT                                additional PKHD1 variant;
FT                                dbSNP:rs1339222045).
FT                                {ECO:0000269|PubMed:28375157}.
FT                                /FTId=VAR_080936.
FT   VARIANT     733    733       Y -> H (in OPPG; dbSNP:rs746701187).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063971.
FT   VARIANT     752    752       R -> G (in EVR4; autosomal recessive;
FT                                dbSNP:rs121908674).
FT                                {ECO:0000269|PubMed:15346351}.
FT                                /FTId=VAR_021223.
FT   VARIANT     798    798       T -> A (in EVR4; dbSNP:rs80358316).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063972.
FT   VARIANT     805    805       R -> W (in EVR4; dbSNP:rs765952535).
FT                                {ECO:0000269|PubMed:19324841}.
FT                                /FTId=VAR_063973.
FT   VARIANT     816    816       Q -> P (rare polymorphism; no effect on
FT                                Norrin signal transduction).
FT                                {ECO:0000269|PubMed:24715757}.
FT                                /FTId=VAR_071014.
FT   VARIANT     852    852       T -> M (in EVR4; de novo mutation found
FT                                in a patient also carrying mutation P-
FT                                540; unknown pathological significance;
FT                                the mutation results in significantly
FT                                reduced Norrin signal transduction;
FT                                dbSNP:rs1398692057).
FT                                {ECO:0000269|PubMed:24715757}.
FT                                /FTId=VAR_071015.
FT   VARIANT     925    925       R -> C (in PCLD4; unknown pathological
FT                                significance; the patient carried
FT                                additional PKHD1 variant;
FT                                dbSNP:rs369471051).
FT                                {ECO:0000269|PubMed:28375157}.
FT                                /FTId=VAR_080937.
FT   VARIANT    1036   1036       R -> Q (in primary osteoporosis; unknown
FT                                pathological significance; found in a
FT                                patient affected by polycystic kidney
FT                                disease; unknown pathological
FT                                significance; dbSNP:rs61889560).
FT                                {ECO:0000269|PubMed:15824851,
FT                                ECO:0000269|PubMed:25920554}.
FT                                /FTId=VAR_063974.
FT   VARIANT    1099   1099       D -> Y (in OPPG).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063975.
FT   VARIANT    1113   1113       R -> C (in OPPG; dbSNP:rs377258285).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063976.
FT   VARIANT    1121   1121       N -> D (in EVR4; unknown pathological
FT                                significance; dbSNP:rs80358317).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063977.
FT   VARIANT    1135   1135       R -> C (in dbSNP:rs143396225).
FT                                {ECO:0000269|PubMed:25920554}.
FT                                /FTId=VAR_080859.
FT   VARIANT    1156   1156       Q -> H (found in a patient affected by
FT                                polycystic kidney disease; unknown
FT                                pathological significance; the patient
FT                                carried pathogenic PKD1 variant; the
FT                                mutation results in significantly reduced
FT                                WNT3A-induced signaling pathway;
FT                                dbSNP:rs724159825).
FT                                {ECO:0000269|PubMed:25920554}.
FT                                /FTId=VAR_080860.
FT   VARIANT    1168   1168       Y -> H (in EVR4; an individual with total
FT                                retinal detachment and retinoschisis; is
FT                                unable to transduce Wnt or Norrin signal
FT                                transduction; dbSNP:rs80358318).
FT                                {ECO:0000269|PubMed:15024691,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_018466.
FT   VARIANT    1188   1188       R -> W (in PCLD4; the mutation results in
FT                                significantly reduced WNT3A-induced
FT                                signaling pathway; dbSNP:rs141178995).
FT                                {ECO:0000269|PubMed:24706814}.
FT                                /FTId=VAR_080861.
FT   VARIANT    1204   1204       V -> L (in dbSNP:rs11607268).
FT                                /FTId=VAR_035208.
FT   VARIANT    1253   1253       C -> F (in EVR4; dbSNP:rs768615287).
FT                                {ECO:0000269|PubMed:20340138}.
FT                                /FTId=VAR_063978.
FT   VARIANT    1330   1330       A -> V (in dbSNP:rs3736228).
FT                                {ECO:0000269|PubMed:12509515,
FT                                ECO:0000269|PubMed:12579474,
FT                                ECO:0000269|PubMed:14727154,
FT                                ECO:0000269|PubMed:15077203}.
FT                                /FTId=VAR_021817.
FT   VARIANT    1361   1361       C -> G (in EVR4; autosomal dominant; has
FT                                mildly reduced Wnt or Norrin signal
FT                                transduction; dbSNP:rs80358320).
FT                                {ECO:0000269|PubMed:15024691,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_018467.
FT   VARIANT    1367   1367       E -> K (in EVR4; autosomal recessive;
FT                                dbSNP:rs28939709).
FT                                {ECO:0000269|PubMed:15346351,
FT                                ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_021224.
FT   VARIANT    1401   1401       G -> D (in OPPG).
FT                                {ECO:0000269|PubMed:16252235}.
FT                                /FTId=VAR_063979.
FT   VARIANT    1517   1517       Y -> C (in EVR1; decreases protein
FT                                abundance; dbSNP:rs201030241).
FT                                {ECO:0000269|PubMed:27228167}.
FT                                /FTId=VAR_076550.
FT   VARIANT    1525   1525       A -> V (in dbSNP:rs1127291).
FT                                {ECO:0000269|PubMed:15024691,
FT                                ECO:0000269|PubMed:9714764}.
FT                                /FTId=VAR_021225.
FT   VARIANT    1529   1529       R -> S (in PCLD4; found in a family
FT                                affected by polycystic liver disease;
FT                                unknown pathological significance).
FT                                {ECO:0000269|PubMed:24706814}.
FT                                /FTId=VAR_080862.
FT   VARIANT    1537   1537       A -> T (could be associated with
FT                                idiopathic osteoporosis; does not result
FT                                in a significant alteration of Wnt signal
FT                                transduction; dbSNP:rs144376510).
FT                                {ECO:0000269|PubMed:16234968}.
FT                                /FTId=VAR_063980.
FT   VARIANT    1540   1540       T -> M (in dbSNP:rs141407040).
FT                                {ECO:0000269|PubMed:15981244}.
FT                                /FTId=VAR_063981.
FT   VARIANT    1541   1541       T -> M (in PCLD4; unknown pathological
FT                                significance; the patient carried
FT                                additional PKHD1 variant;
FT                                dbSNP:rs150862227).
FT                                {ECO:0000269|PubMed:28375157}.
FT                                /FTId=VAR_080938.
FT   VARIANT    1551   1551       D -> N (in PCLD4; unknown pathological
FT                                significance; the mutation results in
FT                                significantly reduced WNT3A-induced
FT                                signaling pathway; dbSNP:rs724159827).
FT                                {ECO:0000269|PubMed:24706814}.
FT                                /FTId=VAR_080863.
FT   CONFLICT   1525   1528       Missing (in Ref. 3; AAK52433).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1615 AA;  179145 MW;  8BA25D07F51E02CA CRC64;
     MEAAPPGPPW PLLLLLLLLL ALCGCPAPAA ASPLLLFANR RDVRLVDAGG VKLESTIVVS
     GLEDAAAVDF QFSKGAVYWT DVSEEAIKQT YLNQTGAAVQ NVVISGLVSP DGLACDWVGK
     KLYWTDSETN RIEVANLNGT SRKVLFWQDL DQPRAIALDP AHGYMYWTDW GETPRIERAG
     MDGSTRKIIV DSDIYWPNGL TIDLEEQKLY WADAKLSFIH RANLDGSFRQ KVVEGSLTHP
     FALTLSGDTL YWTDWQTRSI HACNKRTGGK RKEILSALYS PMDIQVLSQE RQPFFHTRCE
     EDNGGCSHLC LLSPSEPFYT CACPTGVQLQ DNGRTCKAGA EEVLLLARRT DLRRISLDTP
     DFTDIVLQVD DIRHAIAIDY DPLEGYVYWT DDEVRAIRRA YLDGSGAQTL VNTEINDPDG
     IAVDWVARNL YWTDTGTDRI EVTRLNGTSR KILVSEDLDE PRAIALHPVM GLMYWTDWGE
     NPKIECANLD GQERRVLVNA SLGWPNGLAL DLQEGKLYWG DAKTDKIEVI NVDGTKRRTL
     LEDKLPHIFG FTLLGDFIYW TDWQRRSIER VHKVKASRDV IIDQLPDLMG LKAVNVAKVV
     GTNPCADRNG GCSHLCFFTP HATRCGCPIG LELLSDMKTC IVPEAFLVFT SRAAIHRISL
     ETNNNDVAIP LTGVKEASAL DFDVSNNHIY WTDVSLKTIS RAFMNGSSVE HVVEFGLDYP
     EGMAVDWMGK NLYWADTGTN RIEVARLDGQ FRQVLVWRDL DNPRSLALDP TKGYIYWTEW
     GGKPRIVRAF MDGTNCMTLV DKVGRANDLT IDYADQRLYW TDLDTNMIES SNMLGQERVV
     IADDLPHPFG LTQYSDYIYW TDWNLHSIER ADKTSGRNRT LIQGHLDFVM DILVFHSSRQ
     DGLNDCMHNN GQCGQLCLAI PGGHRCGCAS HYTLDPSSRN CSPPTTFLLF SQKSAISRMI
     PDDQHSPDLI LPLHGLRNVK AIDYDPLDKF IYWVDGRQNI KRAKDDGTQP FVLTSLSQGQ
     NPDRQPHDLS IDIYSRTLFW TCEATNTINV HRLSGEAMGV VLRGDRDKPR AIVVNAERGY
     LYFTNMQDRA AKIERAALDG TEREVLFTTG LIRPVALVVD NTLGKLFWVD ADLKRIESCD
     LSGANRLTLE DANIVQPLGL TILGKHLYWI DRQQQMIERV EKTTGDKRTR IQGRVAHLTG
     IHAVEEVSLE EFSAHPCARD NGGCSHICIA KGDGTPRCSC PVHLVLLQNL LTCGEPPTCS
     PDQFACATGE IDCIPGAWRC DGFPECDDQS DEEGCPVCSA AQFPCARGQC VDLRLRCDGE
     ADCQDRSDEA DCDAICLPNQ FRCASGQCVL IKQQCDSFPD CIDGSDELMC EITKPPSDDS
     PAHSSAIGPV IGIILSLFVM GGVYFVCQRV VCQRYAGANG PFPHEYVSGT PHVPLNFIAP
     GGSQHGPFTG IACGKSMMSS VSLMGGRGGV PLYDRNHVTG ASSSSSSSTK ATLYPPILNP
     PPSPATDPSL YNMDMFYSSN IPATARPYRP YIIRGMAPPT TPCSTDVCDS DYSASRWKAS
     KYYLDLNSDS DPYPPPPTPH SQYLSAEDSC PPSPATERSY FHLFPPPPSP CTDSS
//
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