LRP5_HUMAN
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 03-AUG-2022, entry version 205.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Chen D.;
RT "Molecular cloning and characterization of LR3, a novel LDL receptor family
RT 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 for
RT 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., Kim D.H.,
RA Ioka R.X., Ono M., Tomoyori H., Okubo M., Murase T., Kamataki A.,
RA Yamamoto J., Magoori K., Takahashi S., Miyamoto Y., Oishi H., Nose M.,
RA Okazaki M., Usui S., Imaizumi K., Yanagisawa M., Sakai J., Yamamoto T.T.;
RT "Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for
RT normal cholesterol metabolism and glucose-induced 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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [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 project:
RT 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 protein 6
RT maturation.";
RL Biochemistry 46:6570-6577(2007).
RN [9]
RP INTERACTION WITH FZD8 IN WNT-FZD8-LRP5 COMPLEX, INTERACTION WITH DKK1, AND
RP 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., 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 SOST,
RP 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., Hunt D.F.,
RA 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 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., Chen W.,
RA Damagnez V., Bhat R.A., Bex F.J., Bodine P.V.;
RT "A cell-based Dkk1 binding assay reveals roles for extracellular domains of
RT LRP5 in Dkk1 interaction and highlights differences between wild-type and
RT 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., Folz C.,
RA Manning S.P., Swain P.M., Zhao S.-C., Eustace B., Lappe M.M., Spitzer L.,
RA Zweier S., Braunschweiger K., Benchekroun Y., Hu X., Adair R., Chee L.,
RA FitzGerald M.G., Tulig C., Caruso A., Tzellas N., Bawa A., Franklin B.,
RA McGuire S., Nogues X., Gong G., Allen K.M., Anisowicz A., Morales A.J.,
RA Lomedico P.T., Recker S.M., 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 (LRP5)
RT 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., Mackey D.A.,
RA 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 5
RT (LRP5) gene are associated with variation in vertebral bone mass, vertebral
RT 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 associated
RT 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; TRP-570;
RP 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 MET-173;
RP 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 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., Reginato A.M.,
RA Wang H., Cundy T., Glorieux F.H., Lev D., Zacharin M., Oexle K.,
RA Marcelino J., Suwairi W., Heeger S., Sabatakos G., Apte S., Adkins W.N.,
RA Allgrove J., Arslan-Kirchner M., Batch J.A., Beighton P., Black G.C.,
RA Boles R.G., Boon L.M., Borrone C., Brunner H.G., Carle G.F.,
RA Dallapiccola B., De Paepe A., Floege B., Halfhide M.L., Hall B.,
RA Hennekam R.C.M., Hirose T., Jans A., Jueppner H., Kim C.A.,
RA Keppler-Noreuil K., Kohlschuetter A., LaCombe D., Lambert M., Lemyre E.,
RA Letteboer T., Peltonen L., Ramesar R.S., Romanengo M., Somer H.,
RA Steichen-Gersdorf E., Steinmann B., Sullivan B., Superti-Furga A.,
RA Swoboda W., van den Boogaard M.-J., Van Hul W., Vikkula M., Votruba M.,
RA Zabel B., Garcia T., Baron R., Olsen B.R., 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 OF
RP 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., Qu C.,
RA Jiang Z., Li Y., Zhang G., Kim R., Sundaresan P., Yang Z., Zhu X.;
RT "Whole Exome Sequencing Analysis Identifies Mutations in LRP5 in Indian
RT 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; ALA-798
RP 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 exudative
RT vitreoretinopathy with mutations in the LRP5 and/or FZD4 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., Uyguner O.,
RA Bartels C.F., Honing S., Ramirez A., Hanisch F.G., Nurnberg G.,
RA Nurnberg P., Warman M.L., Wollnik B., Kubisch C., 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 novel
RT 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 vitreoretinopathy
RT and Norrie disease with identification of 21 novel variants in FZD4, LRP5,
RT 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., Cole W.G.,
RA Ala-Kokko L., Sochett E.B.;
RT "Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene
RT 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 LRP5
RT mutation.";
RL J. Bone Miner. Res. 20:878-885(2005).
RN [38]
RP VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455, VARIANT THR-1537,
RP CHARACTERIZATION OF VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455,
RP 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., 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 phenotype
RT results in decreased DKK1-mediated inhibition of Wnt 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., Niikawa N.,
RA Yoshiura K.;
RT "LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant
RT 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., Yao Q.,
RA 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., Wu D.,
RA Insogna K., Lifton R.P.;
RT "High bone density due to a mutation in LDL-receptor-related protein 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; SER-1529
RP 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 signaling
RT associated with hepatic cystogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:5343-5348(2014).
RN [45]
RP VARIANTS OPPG ARG-79; GLN-142; ASN-434; PRO-541; ARG-610 AND ASP-1401.
RX PubMed=28192794; DOI=10.1167/iovs.16-20281;
RA Keser V., Khan A., Siddiqui S., Lopez I., Ren H., Qamar R., Nadaf J.,
RA Majewski J., Chen R., Koenekoop R.K.;
RT "The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A
RT Genetic and Phenotypic Study of Pakistani Families.";
RL Invest. Ophthalmol. Vis. Sci. 58:1028-1036(2017).
RN [46]
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., Tahvanainen E.,
RA Tahvanainen P., Sanna-Cherchi S., Lifton R.P., Watnick T., Pei Y.P.,
RA Torres V.E., Somlo S.;
RT "Isolated polycystic liver disease genes define effectors of polycystin-1
RT function.";
RL J. Clin. Invest. 127:1772-1785(2017).
CC -!- FUNCTION: Acts as a coreceptor with members of the frizzled family of
CC seven-transmembrane spanning receptors to transduce signal by Wnt
CC 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 determination
CC and self-renewal during embryonic development and adult tissue
CC regeneration (PubMed:11336703, PubMed:11719191). In particular, may
CC play an important role in the development of the posterior patterning
CC of the epiblast during gastrulation (By similarity). During bone
CC development, regulates osteoblast proliferation and differentiation
CC thus determining bone mass (PubMed:11719191). Mechanistically, the
CC formation of the signaling complex between Wnt ligand, frizzled
CC receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5,
CC stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated
CC transcriptional programs (PubMed:11336703, PubMed:25920554,
CC PubMed:24706814, PubMed:14731402). Acts as a coreceptor for non-Wnt
CC proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-
CC LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling
CC known to be required for retinal vascular development (PubMed:27228167,
CC PubMed:16252235). Plays a role in controlling postnatal vascular
CC regression in retina via macrophage-induced endothelial cell apoptosis
CC (By similarity). {ECO:0000250|UniProtKB:Q91VN0,
CC ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771,
CC ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:14731402,
CC ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:15908424,
CC ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:24706814,
CC ECO:0000269|PubMed:25920554, ECO:0000269|PubMed:27228167}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated oligomer
CC aggregates on Wnt-signaling (By similarity). Component of a Wnt-
CC signaling complex that contains a WNT protein, a FZD protein and LRP5
CC or LRP6. Interacts with FZD8; the interaction is formed on WNT-binding
CC and signaling (PubMed:11448771). Interacts (via the phosphorylated
CC PPPSP motif domains) with AXIN1; the interaction prevents inhibition of
CC beta-catenin phosphorylation and signaling and is enhanced in the
CC presence of GSK3B and WNT1 or WNT3A (PubMed:11336703, PubMed:14731402).
CC Interacts (via beta-propeller regions 3 and 4) with DKK1; the
CC interaction, enhanced by MESD and/or KREMEN, inhibits beta-catenin
CC signaling by preventing GSK3-mediated phosphorylation of the PPPSP
CC motifs and subsequent, AXIN1 binding (PubMed:11448771, PubMed:15778503,
CC PubMed:19746449). Interacts with MESD; the interaction prevents the
CC formation of LRP5 aggregates, targets LRP5 to the plasma membrane and,
CC when complexed with KREMEN2, increases DKK1 binding (PubMed:17488095,
CC PubMed:19746449, PubMed:15143163). Interacts with CSNK1E
CC (PubMed:16513652). Interacts with SOST; the interaction antagonizes
CC canonical Wnt signaling (PubMed:15778503, PubMed:15908424). Interacts
CC with APCDD1 (PubMed:20393562). Interacts with CAPRIN2
CC (PubMed:18762581). {ECO:0000250|UniProtKB:Q91VN0,
CC ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771,
CC ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15143163,
CC ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:15908424,
CC ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17488095,
CC ECO:0000269|PubMed:18762581, ECO:0000269|PubMed:19746449,
CC ECO:0000269|PubMed:20393562}.
CC -!- INTERACTION:
CC O75197; Q8J025: APCDD1; NbExp=3; IntAct=EBI-2466421, EBI-2683489;
CC O75197; Q6IMN6: CAPRIN2; NbExp=3; IntAct=EBI-2466421, EBI-6918449;
CC O75197; Q9BQB4: SOST; NbExp=3; IntAct=EBI-2466421, EBI-5746563;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q91VN0}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:Q91VN0}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:25920554}. Note=Chaperoned to
CC the plasma 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. {ECO:0000269|PubMed:9790987}.
CC -!- PTM: Phosphorylation of cytoplasmic PPPSP motifs regulates the signal
CC transduction of the Wnt signaling pathway through acting as a docking
CC site for AXIN1.
CC -!- POLYMORPHISM: Genetic variations in LRP5 define the bone mineral
CC density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in
CC bone mineral density influences bone mass and contributes to size
CC determination in the general population. {ECO:0000269|PubMed:11741193}.
CC -!- DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: A disorder
CC of the retinal vasculature characterized by an abrupt cessation of
CC growth of peripheral capillaries, leading to an avascular peripheral
CC retina. This may lead to compensatory retinal neovascularization, which
CC is thought to be induced by hypoxia from the initial avascular insult.
CC New vessels are prone to leakage and rupture causing exudates and
CC bleeding, followed by scarring, retinal detachment and blindness.
CC Clinical features can be highly variable, even within the same family.
CC Patients with mild forms of the disease are asymptomatic, and their
CC only disease related abnormality is an arc of avascular retina in the
CC extreme temporal periphery. In many ways the disease resembles
CC retinopathy of prematurity but there is no evidence of prematurity or
CC small birth weight in the patient history.
CC {ECO:0000269|PubMed:27228167}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A disorder
CC of the retinal vasculature characterized by an abrupt cessation of
CC growth of peripheral capillaries, leading to an avascular peripheral
CC retina. This may lead to compensatory retinal neovascularization, which
CC is thought to be induced by hypoxia from the initial avascular insult.
CC New vessels are prone to leakage and rupture causing exudates and
CC bleeding, followed by scarring, retinal detachment and blindness.
CC Clinical features can be highly variable, even within the same family.
CC Patients with mild forms of the disease are asymptomatic, and their
CC only disease related abnormality is an arc of avascular retina in the
CC extreme temporal 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 variants
CC 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 bone
CC microarchitecture without alteration in the composition of bone. The
CC result is fragile bones and an increased risk of fractures, even after
CC minimal trauma. Osteoporosis is a chronic condition of multifactorial
CC etiology and is usually clinically silent until a fracture occurs.
CC {ECO:0000269|PubMed:14727154, ECO:0000269|PubMed:15824851,
CC ECO:0000269|PubMed:16234968}. Note=Disease susceptibility is associated
CC with variants 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 stature,
CC microcephaly, ligamental laxity, intellectual disability and hypotonia.
CC {ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:16252235,
CC ECO:0000269|PubMed:16679074, ECO:0000269|PubMed:17437160,
CC ECO:0000269|PubMed:18602879, ECO:0000269|PubMed:28192794}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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 unusual
CC clinical findings. {ECO:0000269|PubMed:11741193,
CC ECO:0000269|PubMed:12015390, ECO:0000269|PubMed:15143163,
CC ECO:0000269|PubMed:15824861, ECO:0000269|PubMed:17295608}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Endosteal hyperostosis, Worth type (WENHY) [MIM:144750]: An
CC autosomal dominant sclerosing bone dysplasia clinically characterized
CC by elongation of the mandible, increased gonial angle, flattened
CC forehead, and the presence of a slowly enlarging osseous prominence of
CC the hard palate (torus palatinus). Serum calcium, phosphorus and
CC alkaline phosphatase levels are normal. Radiologically, it is
CC characterized by early thickening of the endosteum of long bones, the
CC skull and of the mandible. With advancing age, the trabeculae of the
CC metaphysis become thickened. WENHY becomes clinically and
CC radiologically evident by adolescence, does not cause deformity except
CC in the skull and mandible, and is not associated with bone pain or
CC fracture. Affected patients have normal height, proportion,
CC intelligence and longevity. {ECO:0000269|PubMed:12579474}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Osteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634]: A
CC rare genetic disease characterized by abnormally dense bone, due to
CC defective resorption of immature bone. Osteopetrosis occurs in two
CC forms: a severe autosomal recessive form occurring in utero, infancy,
CC or childhood, and a benign autosomal dominant form occurring in
CC adolescence or adulthood. OPTA1 is an autosomal dominant form
CC characterized by generalized osteosclerosis most pronounced in the
CC cranial vault. Patients are often asymptomatic, but some suffer from
CC pain and hearing loss. It appears to be the only type of osteopetrosis
CC not associated with an increased fracture rate.
CC {ECO:0000269|PubMed:12579474}. Note=The disease is caused by variants
CC 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 cranial
CC osteosclerosis, thickened calvaria and cortices of long bones, enlarged
CC mandible and normal serum alkaline phosphatase levels.
CC {ECO:0000269|PubMed:12579474}. Note=The disease is caused by variants
CC 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 autosomal
CC dominant hepatobiliary disease characterized by overgrowth of biliary
CC epithelium and supportive connective tissue, resulting in multiple
CC liver cysts. PCLD4 patients may also develop kidney cysts that usually
CC do not result in clinically significant renal disease.
CC {ECO:0000269|PubMed:24706814, ECO:0000269|PubMed:28375157}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=LRP5 variations may act as a disease modifier in
CC autosomal dominant polycystic kidney disease (ADPKD) in patients who
CC have causative mutations in PKD1. May contribute to the disease
CC 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 and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/LRP5ID44282ch11q13.html";
CC ---------------------------------------------------------------------------
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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 AlphaFoldDB; O75197; -.
DR SMR; O75197; -.
DR BioGRID; 110220; 145.
DR CORUM; O75197; -.
DR DIP; DIP-47265N; -.
DR ELM; O75197; -.
DR IntAct; O75197; 39.
DR MINT; O75197; -.
DR STRING; 9606.ENSP00000294304; -.
DR ChEMBL; CHEMBL4295675; -.
DR GlyConnect; 1468; 1 N-Linked glycan (1 site).
DR GlyGen; O75197; 6 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O75197; -.
DR PhosphoSitePlus; O75197; -.
DR BioMuta; LRP5; -.
DR EPD; O75197; -.
DR jPOST; O75197; -.
DR MassIVE; O75197; -.
DR PaxDb; O75197; -.
DR PeptideAtlas; O75197; -.
DR PRIDE; O75197; -.
DR ProteomicsDB; 49865; -.
DR ABCD; O75197; 3 sequenced antibodies.
DR Antibodypedia; 4572; 407 antibodies from 37 providers.
DR DNASU; 4041; -.
DR Ensembl; ENST00000294304.12; ENSP00000294304.6; ENSG00000162337.12.
DR GeneID; 4041; -.
DR KEGG; hsa:4041; -.
DR MANE-Select; ENST00000294304.12; ENSP00000294304.6; NM_002335.4; NP_002326.2.
DR UCSC; uc001ont.4; human.
DR CTD; 4041; -.
DR DisGeNET; 4041; -.
DR GeneCards; LRP5; -.
DR HGNC; HGNC:6697; LRP5.
DR HPA; ENSG00000162337; Tissue enhanced (liver).
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 VEuPathDB; HostDB:ENSG00000162337; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000156574; -.
DR HOGENOM; CLU_002489_0_0_1; -.
DR InParanoid; O75197; -.
DR OMA; DMEEFSA; -.
DR OrthoDB; 1008844at2759; -.
DR PhylomeDB; O75197; -.
DR TreeFam; TF315253; -.
DR PathwayCommons; O75197; -.
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; Signaling by LRP5 mutants.
DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants.
DR SignaLink; O75197; -.
DR SIGNOR; O75197; -.
DR BioGRID-ORCS; 4041; 39 hits in 1072 CRISPR screens.
DR ChiTaRS; LRP5; human.
DR GeneWiki; LRP5; -.
DR GenomeRNAi; 4041; -.
DR Pharos; O75197; Tbio.
DR PRO; PR:O75197; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75197; protein.
DR Bgee; ENSG00000162337; Expressed in right lobe of liver and 137 other tissues.
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:0015026; F:coreceptor activity; IBA:GO_Central.
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 receptor activity; IDA:UniProtKB.
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:0060033; P:anatomical structure regression; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:1902262; P:apoptotic process involved in blood vessel morphogenesis; IEA:Ensembl.
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:UniProtKB.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IEA:Ensembl.
DR GO; GO:0060764; P:cell-cell signaling involved in mammary gland development; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; IEA:Ensembl.
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:0008078; P:mesodermal cell migration; IEA:Ensembl.
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:0110135; P:Norrin signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002076; P:osteoblast development; IBA:GO_Central.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
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:0033690; P:positive regulation of osteoblast proliferation; IEA:Ensembl.
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:0042981; P:regulation of apoptotic process; IEA:Ensembl.
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:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR CDD; cd00112; LDLa; 3.
DR Gene3D; 2.120.10.30; -; 4.
DR Gene3D; 4.10.400.10; -; 3.
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 Developmental protein; Disease variant; Disulfide bond; EGF-like domain;
KW Endocytosis; Endoplasmic reticulum; Glycoprotein; Membrane;
KW Osteogenesis imperfecta; Osteopetrosis; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..1615
FT /note="Low-density lipoprotein receptor-related protein 5"
FT /id="PRO_0000017328"
FT TOPO_DOM 32..1384
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1385..1407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1408..1615
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 75..119
FT /note="LDL-receptor class B 1"
FT REPEAT 78..81
FT /note="YWTD 1"
FT REPEAT 120..162
FT /note="LDL-receptor class B 2"
FT REPEAT 123..126
FT /note="YWTD 2"
FT REPEAT 163..206
FT /note="LDL-receptor class B 3"
FT REPEAT 166..169
FT /note="YWTD 3"
FT REPEAT 207..247
FT /note="LDL-receptor class B 4"
FT REPEAT 248..290
FT /note="LDL-receptor class B 5"
FT REPEAT 251..254
FT /note="YWTD 4"
FT DOMAIN 295..337
FT /note="EGF-like 1"
FT REPEAT 385..427
FT /note="LDL-receptor class B 6"
FT REPEAT 388..391
FT /note="YWTD 5"
FT REPEAT 428..470
FT /note="LDL-receptor class B 7"
FT REPEAT 431..434
FT /note="YWTD 6"
FT REPEAT 471..514
FT /note="LDL-receptor class B 8"
FT REPEAT 474..477
FT /note="YWTD 7"
FT REPEAT 515..557
FT /note="LDL-receptor class B 9"
FT REPEAT 558..600
FT /note="LDL-receptor class B 10"
FT REPEAT 559..562
FT /note="YWTD 8"
FT DOMAIN 601..641
FT /note="EGF-like 2"
FT REPEAT 687..729
FT /note="LDL-receptor class B 11"
FT REPEAT 690..693
FT /note="YWTD 9"
FT REPEAT 730..772
FT /note="LDL-receptor class B 12"
FT REPEAT 773..815
FT /note="LDL-receptor class B 13"
FT REPEAT 816..855
FT /note="LDL-receptor class B 14"
FT REPEAT 819..822
FT /note="YWTD 10"
FT REPEAT 856..898
FT /note="LDL-receptor class B 15"
FT REPEAT 859..862
FT /note="YWTD 11"
FT DOMAIN 902..942
FT /note="EGF-like 3"
FT REPEAT 989..1035
FT /note="LDL-receptor class B 16"
FT REPEAT 1036..1078
FT /note="LDL-receptor class B 17"
FT REPEAT 1079..1123
FT /note="LDL-receptor class B 18"
FT REPEAT 1124..1164
FT /note="LDL-receptor class B 19"
FT REPEAT 1165..1207
FT /note="LDL-receptor class B 20"
FT DOMAIN 1213..1254
FT /note="EGF-like 4"
FT DOMAIN 1258..1296
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1297..1333
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1335..1371
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REGION 32..288
FT /note="Beta-propeller 1"
FT REGION 341..602
FT /note="Beta-propeller 2"
FT REGION 644..903
FT /note="Beta-propeller 3"
FT REGION 945..1212
FT /note="Beta-propeller 4"
FT REGION 1475..1501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1568..1615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1500..1506
FT /note="PPPSP motif A"
FT MOTIF 1538..1545
FT /note="PPPSP motif B"
FT MOTIF 1574..1581
FT /note="PPPSP motif C"
FT MOTIF 1591..1596
FT /note="PPPSP motif D"
FT MOTIF 1605..1612
FT /note="PPPSP motif E"
FT COMPBIAS 1477..1494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1601..1615
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 705
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 878
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 299..310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 306..321
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 323..336
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 605..616
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 612..625
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 627..640
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 906..917
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 913..926
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 928..941
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1217..1228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1224..1238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1240..1253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1259..1273
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1266..1286
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1280..1295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1298..1310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1305..1323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1317..1332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1336..1348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1343..1361
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1355..1370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT VARIANT 15..20
FT /note="Missing (found in a family with osteoporosis
FT pseudoglioma syndrome; impairs protein trafficking to the
FT endoplasmic reticulum and cell membrane)"
FT /evidence="ECO:0000269|PubMed:19177549"
FT /id="VAR_058582"
FT VARIANT 18..20
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021804"
FT VARIANT 20
FT /note="L -> LL"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021805"
FT VARIANT 29
FT /note="A -> T (in primary osteoporosis)"
FT /evidence="ECO:0000269|PubMed:15824851"
FT /id="VAR_063941"
FT VARIANT 79
FT /note="W -> R (in OPPG; unknown pathological significance;
FT dbSNP:rs1197978360)"
FT /evidence="ECO:0000269|PubMed:28192794"
FT /id="VAR_085732"
FT VARIANT 89
FT /note="Q -> R (in dbSNP:rs41494349)"
FT /evidence="ECO:0000269|PubMed:12579474,
FT ECO:0000269|PubMed:14727154"
FT /id="VAR_021806"
FT VARIANT 97
FT /note="A -> V (in dbSNP:rs143433231)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063942"
FT VARIANT 111
FT /note="D -> Y (in OPTA1)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021807"
FT VARIANT 142
FT /note="R -> Q (in OPPG; unknown pathological significance;
FT dbSNP:rs368198391)"
FT /evidence="ECO:0000269|PubMed:28192794"
FT /id="VAR_085733"
FT VARIANT 145
FT /note="L -> F (in EVR4; dbSNP:rs80358305)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063943"
FT VARIANT 154
FT /note="R -> M (in HBM)"
FT /evidence="ECO:0000269|PubMed:15824861"
FT /id="VAR_063944"
FT VARIANT 171
FT /note="G -> R (in OPTA1; dbSNP:rs121908669)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021808"
FT VARIANT 171
FT /note="G -> V (in HBM; also in HBM individuals with
FT enlarged mandible and torus palatinus; abolishes
FT interaction with MESD; impairs transport to cell surface;
FT no enhancement of DKK1 binding by MESD resulting in
FT impaired inhibition of Wnt signaling by DKK1;
FT dbSNP:rs121908668)"
FT /evidence="ECO:0000269|PubMed:11741193,
FT ECO:0000269|PubMed:12015390, ECO:0000269|PubMed:15143163,
FT ECO:0000269|PubMed:19746449"
FT /id="VAR_021809"
FT VARIANT 173
FT /note="T -> M (in EVR4; an individual with abnormal retinal
FT vasculature and retinal folds; dbSNP:rs80358306)"
FT /evidence="ECO:0000269|PubMed:15024691,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_018465"
FT VARIANT 203
FT /note="D -> N (in OPPG; dbSNP:rs760548029)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063945"
FT VARIANT 214
FT /note="A -> T (in WENHY; dbSNP:rs121908671)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021810"
FT VARIANT 214
FT /note="A -> V (in WENHY; dbSNP:rs121908672)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021811"
FT VARIANT 242
FT /note="A -> T (in OPTA1, VBCH2 and WENHY;
FT dbSNP:rs121908670)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021812"
FT VARIANT 244
FT /note="T -> M (in OPPG; appears to traffic less well than
FT does the wild-type protein; appears to be post-
FT translationally modified similar to wild-type protein; is
FT unable to transduce Wnt signal; has a significantly reduced
FT ability to transduce Norrin signal; dbSNP:rs397514665)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063946"
FT VARIANT 253
FT /note="T -> I (in OPTA1; dbSNP:rs121908673)"
FT /evidence="ECO:0000269|PubMed:12579474"
FT /id="VAR_021813"
FT VARIANT 282
FT /note="M -> V (in HBM; unknown pathological significance;
FT lowered LRP5-mediated Wnt signaling; no effect on DKK1
FT binding)"
FT /evidence="ECO:0000269|PubMed:17295608"
FT /id="VAR_063412"
FT VARIANT 307
FT /note="S -> F (in OPPG; dbSNP:rs1219101402)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063947"
FT VARIANT 348
FT /note="R -> W (in OPPG and EVR1; reduces Norrin signal
FT transduction; dbSNP:rs1320065036)"
FT /evidence="ECO:0000269|PubMed:16252235,
FT ECO:0000269|PubMed:27228167"
FT /id="VAR_063948"
FT VARIANT 353
FT /note="R -> Q (in OPPG)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063949"
FT VARIANT 356
FT /note="S -> L (in idiopathic osteoporosis and OPPG; appears
FT to traffic comparably than does the wild-type protein;
FT appears to be post-translationally modified similar to
FT wild-type protein; is unable to transduce Wnt signal; has a
FT significantly reduced ability to transduce Norrin signal;
FT dbSNP:rs1158745675)"
FT /evidence="ECO:0000269|PubMed:16234968,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_063950"
FT VARIANT 381
FT /note="D -> N (in EVR1; reduces Norrin signal transduction;
FT dbSNP:rs1332274863)"
FT /evidence="ECO:0000269|PubMed:27228167"
FT /id="VAR_076548"
FT VARIANT 390
FT /note="T -> K (in OPPG; is unable to traffic normally;
FT appears to be post-translationally modified similar to
FT wild-type protein; is unable to transduce Wnt signal; has a
FT significantly reduced ability to transduce Norrin signal)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063951"
FT VARIANT 400
FT /note="A -> E (in OPPG; dbSNP:rs201320326)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063952"
FT VARIANT 404
FT /note="G -> R (in OPPG; appears to traffic less well than
FT does the wild-type protein; appears to be post-
FT translationally modified similar to wild-type protein; has
FT 50% of wild-type activity to transduce Wnt signal; has a
FT significantly reduced ability to transduce Norrin signal;
FT dbSNP:rs750791263)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063953"
FT VARIANT 409
FT /note="T -> A (in OPPG; dbSNP:rs1273567061)"
FT /evidence="ECO:0000269|PubMed:18602879"
FT /id="VAR_063954"
FT VARIANT 422
FT /note="A -> T (in EVR4; the mutation results in
FT significantly reduced Norrin signal transduction;
FT dbSNP:rs774342727)"
FT /evidence="ECO:0000269|PubMed:24715757"
FT /id="VAR_071012"
FT VARIANT 434
FT /note="D -> N (in OPPG; unknown pathological significance;
FT appears to traffic less well than does the wild-type
FT protein; appears to be post-translationally modified
FT similar to wild-type protein; has 50% of wild-type activity
FT to transduce Wnt signal; has a significantly reduced
FT ability to transduce Norrin signal; dbSNP:rs757888034)"
FT /evidence="ECO:0000269|PubMed:16252235,
FT ECO:0000269|PubMed:28192794"
FT /id="VAR_063955"
FT VARIANT 441
FT /note="E -> K (in EVR4; dbSNP:rs376152274)"
FT /evidence="ECO:0000269|PubMed:20340138"
FT /id="VAR_063956"
FT VARIANT 444
FT /note="R -> C (in EVR4; associated in a EVR1 patient with
FT mutation GLN-417 in FZD4; dbSNP:rs80358308)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063957"
FT VARIANT 454
FT /note="V -> M (in PCLD4; unknown pathological significance;
FT dbSNP:rs373910016)"
FT /evidence="ECO:0000269|PubMed:24706814"
FT /id="VAR_080857"
FT VARIANT 455
FT /note="S -> L (in idiopathic osteoporosis; shows an
FT inhibitory effect on Wnt signal transduction;
FT dbSNP:rs930355318)"
FT /evidence="ECO:0000269|PubMed:16234968"
FT /id="VAR_063958"
FT VARIANT 460
FT /note="E -> K (in OPPG; dbSNP:rs866606166)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063959"
FT VARIANT 478
FT /note="W -> R (in OPPG; dbSNP:rs1318906451)"
FT /evidence="ECO:0000269|PubMed:16679074"
FT /id="VAR_063960"
FT VARIANT 494
FT /note="R -> Q (in OPPG; dbSNP:rs121908664)"
FT /evidence="ECO:0000269|PubMed:11719191,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_021814"
FT VARIANT 504
FT /note="W -> C (in OPPG; dbSNP:rs545508982)"
FT /evidence="ECO:0000269|PubMed:16679074"
FT /id="VAR_063961"
FT VARIANT 511
FT /note="D -> A (in EVR4; dbSNP:rs1245625202)"
FT /evidence="ECO:0000269|PubMed:19324841"
FT /id="VAR_063962"
FT VARIANT 520
FT /note="G -> V (in OPPG; appears to traffic comparably than
FT does the wild-type protein; appears to be post-
FT translationally modified similar to wild-type protein; is
FT unable to transduce Wnt signal; has a significantly reduced
FT ability to transduce Norrin signal)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063963"
FT VARIANT 522
FT /note="A -> T (in EVR4; dbSNP:rs80358309)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063964"
FT VARIANT 531
FT /note="N -> I (in OPPG)"
FT /evidence="ECO:0000269|PubMed:17437160"
FT /id="VAR_063965"
FT VARIANT 535
FT /note="T -> M (in EVR4; autosomal recessive;
FT dbSNP:rs80358310)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063966"
FT VARIANT 540
FT /note="L -> P (in EVR4; the mutation results in
FT significantly reduced Norrin signal transduction)"
FT /evidence="ECO:0000269|PubMed:24715757"
FT /id="VAR_071013"
FT VARIANT 541
FT /note="L -> P (in OPPG; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28192794"
FT /id="VAR_085734"
FT VARIANT 550
FT /note="G -> R (in EVR4; autosomal recessive;
FT dbSNP:rs80358311)"
FT /evidence="ECO:0000269|PubMed:16929062"
FT /id="VAR_063967"
FT VARIANT 560
FT /note="W -> C (found in a family affected by polycystic
FT kidney and liver disease; unknown pathological
FT significance; the patients carried additional PKD1
FT variants; the mutation results in significantly reduced
FT WNT3A-induced signaling pathway; dbSNP:rs377144001)"
FT /evidence="ECO:0000269|PubMed:25920554"
FT /id="VAR_080858"
FT VARIANT 570
FT /note="R -> Q (in EVR4; autosomal recessive; has
FT significantly reduced Wnt or Norrin signal transduction;
FT dbSNP:rs80358312)"
FT /evidence="ECO:0000269|PubMed:15346351,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_021222"
FT VARIANT 570
FT /note="R -> W (in OPPG; dbSNP:rs121908665)"
FT /evidence="ECO:0000269|PubMed:11719191,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_021815"
FT VARIANT 610
FT /note="G -> R (in EVR4 and OPPG; unknown pathological
FT significance; appears to traffic less well than does the
FT wild-type protein; appears to be post-translationally
FT modified similar to wild-type protein; has 60% of wild-type
FT activity to transduce Wnt signal; has a significantly
FT reduced ability to transduce Norrin signal;
FT dbSNP:rs80358313)"
FT /evidence="ECO:0000269|PubMed:15981244,
FT ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:28192794"
FT /id="VAR_063968"
FT VARIANT 617
FT /note="F -> C (in EVR4; autosomal recessive;
FT dbSNP:rs80358314)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063969"
FT VARIANT 624
FT /note="R -> W (in EVR1; reduces Norrin signal transduction;
FT dbSNP:rs989864153)"
FT /evidence="ECO:0000269|PubMed:27228167"
FT /id="VAR_076549"
FT VARIANT 638
FT /note="K -> E (in PCLD4; unknown pathological significance;
FT the patient carried additional PKHD1 variant;
FT dbSNP:rs758976409)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080935"
FT VARIANT 667
FT /note="V -> M (in dbSNP:rs4988321)"
FT /evidence="ECO:0000269|PubMed:11719191,
FT ECO:0000269|PubMed:12579474, ECO:0000269|PubMed:15077203"
FT /id="VAR_021816"
FT VARIANT 683
FT /note="D -> N (in OPPG; dbSNP:rs1470530779)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063970"
FT VARIANT 684
FT /note="V -> A (in PCLD4; unknown pathological significance;
FT the patient carried additional PKHD1 variant;
FT dbSNP:rs1339222045)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080936"
FT VARIANT 733
FT /note="Y -> H (in OPPG; dbSNP:rs746701187)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063971"
FT VARIANT 752
FT /note="R -> G (in EVR4; autosomal recessive;
FT dbSNP:rs121908674)"
FT /evidence="ECO:0000269|PubMed:15346351"
FT /id="VAR_021223"
FT VARIANT 798
FT /note="T -> A (in EVR4; dbSNP:rs80358316)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063972"
FT VARIANT 805
FT /note="R -> W (in EVR4; dbSNP:rs765952535)"
FT /evidence="ECO:0000269|PubMed:19324841"
FT /id="VAR_063973"
FT VARIANT 816
FT /note="Q -> P (likely benign variant; no effect on Norrin
FT signal transduction)"
FT /evidence="ECO:0000269|PubMed:24715757"
FT /id="VAR_071014"
FT VARIANT 852
FT /note="T -> M (in EVR4; de novo mutation found in a patient
FT also carrying mutation P-540; unknown pathological
FT significance; the mutation results in significantly reduced
FT Norrin signal transduction; dbSNP:rs1398692057)"
FT /evidence="ECO:0000269|PubMed:24715757"
FT /id="VAR_071015"
FT VARIANT 925
FT /note="R -> C (in PCLD4; unknown pathological significance;
FT the patient carried additional PKHD1 variant;
FT dbSNP:rs369471051)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080937"
FT VARIANT 1036
FT /note="R -> Q (in primary osteoporosis; unknown
FT pathological significance; found in a patient affected by
FT polycystic kidney disease; unknown pathological
FT significance; dbSNP:rs61889560)"
FT /evidence="ECO:0000269|PubMed:15824851,
FT ECO:0000269|PubMed:25920554"
FT /id="VAR_063974"
FT VARIANT 1099
FT /note="D -> Y (in OPPG)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063975"
FT VARIANT 1113
FT /note="R -> C (in OPPG; dbSNP:rs377258285)"
FT /evidence="ECO:0000269|PubMed:16252235"
FT /id="VAR_063976"
FT VARIANT 1121
FT /note="N -> D (in EVR4; unknown pathological significance;
FT dbSNP:rs80358317)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063977"
FT VARIANT 1135
FT /note="R -> C (in dbSNP:rs143396225)"
FT /evidence="ECO:0000269|PubMed:25920554"
FT /id="VAR_080859"
FT VARIANT 1156
FT /note="Q -> H (found in a patient affected by polycystic
FT kidney disease; unknown pathological significance; the
FT patient carried pathogenic PKD1 variant; the mutation
FT results in significantly reduced WNT3A-induced signaling
FT pathway; dbSNP:rs724159825)"
FT /evidence="ECO:0000269|PubMed:25920554"
FT /id="VAR_080860"
FT VARIANT 1168
FT /note="Y -> H (in EVR4; an individual with total retinal
FT detachment and retinoschisis; is unable to transduce Wnt or
FT Norrin signal transduction; dbSNP:rs80358318)"
FT /evidence="ECO:0000269|PubMed:15024691,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_018466"
FT VARIANT 1188
FT /note="R -> W (in PCLD4; the mutation results in
FT significantly reduced WNT3A-induced signaling pathway;
FT dbSNP:rs141178995)"
FT /evidence="ECO:0000269|PubMed:24706814"
FT /id="VAR_080861"
FT VARIANT 1204
FT /note="V -> L (in dbSNP:rs11607268)"
FT /id="VAR_035208"
FT VARIANT 1253
FT /note="C -> F (in EVR4; dbSNP:rs768615287)"
FT /evidence="ECO:0000269|PubMed:20340138"
FT /id="VAR_063978"
FT VARIANT 1330
FT /note="A -> V (in dbSNP:rs3736228)"
FT /evidence="ECO:0000269|PubMed:12509515,
FT ECO:0000269|PubMed:12579474, ECO:0000269|PubMed:14727154,
FT ECO:0000269|PubMed:15077203"
FT /id="VAR_021817"
FT VARIANT 1361
FT /note="C -> G (in EVR4; autosomal dominant; has mildly
FT reduced Wnt or Norrin signal transduction;
FT dbSNP:rs80358320)"
FT /evidence="ECO:0000269|PubMed:15024691,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_018467"
FT VARIANT 1367
FT /note="E -> K (in EVR4; autosomal recessive;
FT dbSNP:rs28939709)"
FT /evidence="ECO:0000269|PubMed:15346351,
FT ECO:0000269|PubMed:16252235"
FT /id="VAR_021224"
FT VARIANT 1401
FT /note="G -> D (in OPPG; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:16252235,
FT ECO:0000269|PubMed:28192794"
FT /id="VAR_063979"
FT VARIANT 1517
FT /note="Y -> C (in EVR1; decreases protein abundance;
FT dbSNP:rs201030241)"
FT /evidence="ECO:0000269|PubMed:27228167"
FT /id="VAR_076550"
FT VARIANT 1525
FT /note="A -> V (in dbSNP:rs1127291)"
FT /evidence="ECO:0000269|PubMed:15024691,
FT ECO:0000269|PubMed:9714764"
FT /id="VAR_021225"
FT VARIANT 1529
FT /note="R -> S (in PCLD4; found in a family affected by
FT polycystic liver disease; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24706814"
FT /id="VAR_080862"
FT VARIANT 1537
FT /note="A -> T (could be associated with idiopathic
FT osteoporosis; does not result in a significant alteration
FT of Wnt signal transduction; dbSNP:rs144376510)"
FT /evidence="ECO:0000269|PubMed:16234968"
FT /id="VAR_063980"
FT VARIANT 1540
FT /note="T -> M (in dbSNP:rs141407040)"
FT /evidence="ECO:0000269|PubMed:15981244"
FT /id="VAR_063981"
FT VARIANT 1541
FT /note="T -> M (in PCLD4; unknown pathological significance;
FT the patient carried additional PKHD1 variant;
FT dbSNP:rs150862227)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080938"
FT VARIANT 1551
FT /note="D -> N (in PCLD4; unknown pathological significance;
FT the mutation results in significantly reduced WNT3A-induced
FT signaling pathway; dbSNP:rs724159827)"
FT /evidence="ECO:0000269|PubMed:24706814"
FT /id="VAR_080863"
FT CONFLICT 1525..1528
FT /note="Missing (in Ref. 3; AAK52433)"
FT /evidence="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
