This gene encodes a secreted protein with a cystein-knot motif that activates the Wnt/beta-catenin pathway. The protein forms disulfide-linked oligomers in the extracellular matrix. Mutations in this gene result in Norrie disease and X-linked exudative vitreoretinopathy. [provided by RefSeq, Feb 2009]
Function:
Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction.
Subcellular Location:
Secreted.
Tissue Specificity:
Expressed in the outer nuclear, inner nuclear and ganglion cell layers of the retina, and in fetal and adult brain.
DISEASE:
Defects in NDP are the cause of Norrie disease (ND) [MIM:310600]; also known as atrophia bulborum hereditaria or Episkopi blindness. ND is a recessive disorder characterized by very early childhood blindness due to degenerative and proliferative changes of the neuroretina. Approximately 50% of patients show some form of progressive mental disorder, often with psychotic features, and about one-third of patients develop sensorineural deafness in the second decade. In addition, some patients have more complex phenotypes, including growth failure and seizure.
Defects in NDP are the cause of vitreoretinopathy exudative type 2 (EVR2) [MIM:305390]. EVR2 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.
Similarity:
Contains 1 CTCK (SLCterminal cystine knot-like) domain.
SWISS:
Q00604
Gene ID:
4693
Database links:
Entrez Gene: 4693 Human
Entrez Gene: 418560 Chicken
Entrez Gene: 61288 Dog
Entrez Gene: 17986 Mouse
Entrez Gene: 363443 Rat
Omim: 300658 Human
SwissProt: Q2KI78 Cow
SwissProt: Q00604 Human
SwissProt: P48744 Mouse
Unigene: 522615 Human
Unigene: 5014 Mouse
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