LRP5
entrez
4041
canonical
uniprot
O75197
canonical
ensembl
ENSG00000162337
resolver
ensp
ENSP00000294304
resolver
enst
ENST00000294304
resolver
genesymbol
LRP5
resolver
genesymbol_syn
LR3
resolver
genesymbol_syn
LRP7
resolver
hgnc
HGNC:6697
resolver
uniprot
Q96TD6
resolver
uniprot
Q9UES7
resolver
uniprot
Q9UP66
resolver
uniprot_entry
LRP5_HUMAN
resolver
uniprot_sec
Q96TD6
resolver
uniprot_sec
Q9UES7
resolver
uniprot_sec
Q9UP66
resolver
amino_acid_sequence
MEAAPPGPPWPLLLLLLLLLALCGCPAPAAASPLLLFANRRDVRLVDAGGVKLESTIVVSGLEDAAAVDFQFSKGAVYWTDVSEEAIKQTYLNQTGAAVQNVVISGLVSPDGLACDWVGKKLYWTDSETNRIEVANLNGTSRKVLFWQDLDQPRAIALDPAHGYMYWTDWGETPRIERAGMDGSTRKIIVDSDIYWPNGLTIDLEEQKLYWADAKLSFIHRANLDGSFRQKVVEGSLTHPFALTLSGDTLYWTDWQTRSIHACNKRTGGKRKEILSALYSPMDIQVLSQERQPFFHTRCEEDNGGCSHLCLLSPSEPFYTCACPTGVQLQDNGRTCKAGAEEVLLLARRTDLRRISLDTPDFTDIVLQVDDIRHAIAIDYDPLEGYVYWTDDEVRAIRRAYLDGSGAQTLVNTEINDPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTSRKILVSEDLDEPRAIALHPVMGLMYWTDWGENPKIECANLDGQERRVLVNASLGWPNGLALDLQEGKLYWGDAKTDKIEVINVDGTKRRTLLEDKLPHIFGFTLLGDFIYWTDWQRRSIERVHKVKASRDVIIDQLPDLMGLKAVNVAKVVGTNPCADRNGGCSHLCFFTPHATRCGCPIGLELLSDMKTCIVPEAFLVFTSRAAIHRISLETNNNDVAIPLTGVKEASALDFDVSNNHIYWTDVSLKTISRAFMNGSSVEHVVEFGLDYPEGMAVDWMGKNLYWADTGTNRIEVARLDGQFRQVLVWRDLDNPRSLALDPTKGYIYWTEWGGKPRIVRAFMDGTNCMTLVDKVGRANDLTIDYADQRLYWTDLDTNMIESSNMLGQERVVIADDLPHPFGLTQYSDYIYWTDWNLHSIERADKTSGRNRTLIQGHLDFVMDILVFHSSRQDGLNDCMHNNGQCGQLCLAIPGGHRCGCASHYTLDPSSRNCSPPTTFLLFSQKSAISRMIPDDQHSPDLILPLHGLRNVKAIDYDPLDKFIYWVDGRQNIKRAKDDGTQPFVLTSLSQGQNPDRQPHDLSIDIYSRTLFWTCEATNTINVHRLSGEAMGVVLRGDRDKPRAIVVNAERGYLYFTNMQDRAAKIERAALDGTEREVLFTTGLIRPVALVVDNTLGKLFWVDADLKRIESCDLSGANRLTLEDANIVQPLGLTILGKHLYWIDRQQQMIERVEKTTGDKRTRIQGRVAHLTGIHAVEEVSLEEFSAHPCARDNGGCSHICIAKGDGTPRCSCPVHLVLLQNLLTCGEPPTCSPDQFACATGEIDCIPGAWRCDGFPECDDQSDEEGCPVCSAAQFPCARGQCVDLRLRCDGEADCQDRSDEADCDAICLPNQFRCASGQCVLIKQQCDSFPDCIDGSDELMCEITKPPSDDSPAHSSAIGPVIGIILSLFVMGGVYFVCQRVVCQRYAGANGPFPHEYVSGTPHVPLNFIAPGGSQHGPFTGIACGKSMMSSVSLMGGRGGVPLYDRNHVTGASSSSSSSTKATLYPPILNPPPSPATDPSLYNMDMFYSSNIPATARPYRPYIIRGMAPPTTPCSTDVCDSDYSASRWKASKYYLDLNSDSDPYPPPPTPHSQYLSAEDSCPPSPATERSYFHLFPPPPSPCTDSS
uniprot
proteins
disease_involvement
DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: An autosomal dominant disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history. {ECO:0000269|PubMed:27228167}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. EVR4 inheritance can be autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:15024691, ECO:0000269|PubMed:15346351, ECO:0000269|PubMed:15981244, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16929062, ECO:0000269|PubMed:19324841, ECO:0000269|PubMed:20340138, ECO:0000269|PubMed:24715757}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. {ECO:0000269|PubMed:14727154, ECO:0000269|PubMed:15824851, ECO:0000269|PubMed:16234968}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Osteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770]: A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures. Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, intellectual disability and hypotonia. {ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16679074, ECO:0000269|PubMed:17437160, ECO:0000269|PubMed:18602879, ECO:0000269|PubMed:28192794}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: High bone mass trait (HBM) [MIM:601884]: Rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings. {ECO:0000269|PubMed:11741193, ECO:0000269|PubMed:12015390, ECO:0000269|PubMed:15143163, ECO:0000269|PubMed:15824861, ECO:0000269|PubMed:17295608}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Endosteal hyperostosis, Worth type (WENHY) [MIM:144750]: An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus). Serum calcium, phosphorus and alkaline phosphatase levels are normal. Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible. With advancing age, the trabeculae of the metaphysis become thickened. WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture. Affected patients have normal height, proportion, intelligence and longevity. {ECO:0000269|PubMed:12579474}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Osteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate. {ECO:0000269|PubMed:12579474}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Van Buchem disease 2 (VBCH2) [MIM:607636]: VBCH2 is an autosomal dominant sclerosing bone dysplasia characterized by cranial osteosclerosis, thickened calvaria and cortices of long bones, enlarged mandible and normal serum alkaline phosphatase levels. {ECO:0000269|PubMed:12579474}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Polycystic liver disease 4 with or without kidney cysts (PCLD4) [MIM:617875]: A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD4 patients may also develop kidney cysts that usually do not result in clinically significant renal disease. {ECO:0000269|PubMed:24706814, ECO:0000269|PubMed:28375157}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=LRP5 variations may act as a disease modifier in autosomal dominant polycystic kidney disease (ADPKD) in patients who have causative mutations in PKD1. May contribute to the disease phenotype heterogeneity and hepatic cystogenesis. {ECO:0000269|PubMed:25920554}.
uniprot
proteins
function
FUNCTION: Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins (PubMed:11336703, PubMed:11448771, PubMed:11719191, PubMed:15778503, PubMed:15908424, PubMed:16252235). Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration (PubMed:11336703, PubMed:11719191). In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation (By similarity). During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass (PubMed:11719191). Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs (PubMed:11336703, PubMed:14731402, PubMed:24706814, PubMed:25920554). Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development (PubMed:16252235, PubMed:27228167). Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis (By similarity). {ECO:0000250|UniProtKB:Q91VN0, ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:15908424, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:24706814, ECO:0000269|PubMed:25920554, ECO:0000269|PubMed:27228167}.
uniprot
proteins
mass_dalton
179145
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.
uniprot
proteins
protein_family
LDLR family
uniprot
proteins
pubmed
11336703
uniprot
proteins
pubmed
11401438
uniprot
proteins
pubmed
11448771
uniprot
proteins
pubmed
11719191
uniprot
proteins
pubmed
11741193
uniprot
proteins
pubmed
12015390
uniprot
proteins
pubmed
12509515
uniprot
proteins
pubmed
12579474
uniprot
proteins
pubmed
14727154
uniprot
proteins
pubmed
14731402
uniprot
proteins
pubmed
15024691
uniprot
proteins
pubmed
15077203
uniprot
proteins
pubmed
15143163
uniprot
proteins
pubmed
15346351
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15778503
uniprot
proteins
pubmed
15824851
uniprot
proteins
pubmed
15824861
uniprot
proteins
pubmed
15908424
uniprot
proteins
pubmed
15981244
uniprot
proteins
pubmed
16234968
uniprot
proteins
pubmed
16252235
uniprot
proteins
pubmed
16513652
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16679074
uniprot
proteins
pubmed
16929062
uniprot
proteins
pubmed
17295608
uniprot
proteins
pubmed
17437160
uniprot
proteins
pubmed
17488095
uniprot
proteins
pubmed
18602879
uniprot
proteins
pubmed
18762581
uniprot
proteins
pubmed
19177549
uniprot
proteins
pubmed
19324841
uniprot
proteins
pubmed
19746449
uniprot
proteins
pubmed
20340138
uniprot
proteins
pubmed
20393562
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24706814
uniprot
proteins
pubmed
24715757
uniprot
proteins
pubmed
25920554
uniprot
proteins
pubmed
27228167
uniprot
proteins
pubmed
28192794
uniprot
proteins
pubmed
28375157
uniprot
proteins
pubmed
9714764
uniprot
proteins
pubmed
9790987
uniprot
proteins
sequence_length
1615
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q91VN0}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q91VN0}. Endoplasmic reticulum {ECO:0000269|PubMed:25920554}. Note=Chaperoned to the plasma membrane by MESD. {ECO:0000250|UniProtKB:Q91VN0}.
uniprot
proteins
transmembrane_region
TRANSMEM 1385..1407; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins