背景介绍
This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014],
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disease:Defects in LRP5 are a cause of endosteal hyperostosis Worth type (WENHY) [MIM:144750]; also known as autosomal dominant osteosclerosis. WENHY is an autosomal dominant sclerosing bone dysplasia clinically characterizd 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.,disease:Defects in LRP5 are a cause of high bone mass trait (HBM) [MIM:601884]. HBM is a rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings.,disease:Defects in LRP5 are the cause of osteopetrosis autosomal dominant type 1 (OPTA1) [MIM:607634]. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder 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 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.,disease:Defects in LRP5 are the cause of osteoporosis pseudoglioma syndrome (OPPG) [MIM:259770]. OPPG is a recessive disorder characterized by very low bone mass and blindness. Individualy with OPPG are prone to develop bone fractures and deformations and have various eye abnormalities, including phthisis bulbi, retinal detachments, falciform folds or persistent vitreal vasculature.,disease:Defects in LRP5 are the cause of van Buchem disease type 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.,disease:Defects in LRP5 are the cause of vitreoretinopathy exudative type 4 (EVR4) [MIM:601813]. EVR4 is 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 recessive.,disease:Genetic variations in LRP5 may be associated with susceptibility to involutional osteoporosis [MIM:166710]; also known as senile osteoporosis or postmenopausal osteoporosis. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.,function:Involved in the Wnt/beta catenin signaling pathway, probably by acting as a coreceptor together with Frizzled for Wnt.,polymorphism:Genetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population.,PTM:Phosphorylation of the PPPSP motif creates an inducible docking site for axin.,similarity:Belongs to the LDLR family.,similarity:Contains 20 LDL-receptor class B repeats.,similarity:Contains 3 LDL-receptor class A domains.,similarity:Contains 4 EGF-like domains.,subunit:Interacts with different Wnt/Frizzled complexes. Interacts with axin.,tissue specificity:Widely expressed, with the highest level of expression in the liver.,
