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"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; 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 //