Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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frizzled class receptor 4(FZD4) frizzled class receptor 4(FZD4) Related Genes Homo sapiens
CYTOBAND 11q14.2,
GENERIF_SUMMARY Functions in retinal angiogenesis. Mutations disrupts angiogenesis in vitreoretinopathy., High-resolution genotyping and haplotype analysis excluded FZD4 as the defective gene in a family previously linked to the EVR1 locus., Familial exudative vitreoretinopathy has mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor, Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR (familial exudative vitreoretinopathy), FZD4 mutations are associated with autosomal dominant familial exudative vitreoretinopathy, A novel missense mutation in the FZD4 gene was identified in Japanese patients with FEVR (familial exudative vitreoretinopathy)., mutations in the LRP5 and/or FZD4 genes may have roles in familial exudative vitreoretinopathy, Mutations in FZD4 were observed in 5.6% of studied clinically diagnosed familial exudative vitreoretinopathy in Indian population. Could play vital role in pathogenesis and provide greater insight in to genotype/phenotypic functions of FZD4 gene., Fz4 expression may play a critical role in responses to Wnt signaling in the tumor microenvironment., sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity in cooperation with GSK-3beta, Homozygous state for the FZD4 gene is possibly involved in the severity of the familial exudative vitreoretinopathy phenotype, Report activation of Wnt signalling in acute myeloid leukemia by induction of Frizzled-4., The clinical features in the three children and their relatives with a documented FZD4 mutation support the previous reports of a high degree of intrafamilial and interfamilial variability in familial exudative vitreoretinopathy (FEVR)., Mutations occurring in the FZD4 gene affect patients diagnosed with both autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP), Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe retinopathy of prematurity., Studies report 21 novel variants for FZD4, LRP5, and NDP., Results provide mechanistic insights to ERG oncogenesis in prostate cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion., The profile of the mutations obtained in FZD4 further illustrates the complexity of familial exudative vitreoretinopathy (FEVR)and provides a better understanding of the genotype-phenotype correlations., FZD4 mutation screening can be a useful tool especially in mild or atypical cases of familial exudative vitreoretinopathy & Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease., Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis., miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4., Genetic analysis revealed that all affected family members of one pedigree carried an exon 2 mutation of COL2A1, and in the second pedigree, all affected members carried an FZD4 mutation., Five mutations have been found in the FZD4 gene in six Chinese families with familial exudative vitreoretinopathy., Six different nonsynonymous DNA variants are identified in the coding region of either the FZD4 gene (p.H69Y, p.R127H, and p.Y211H) or the LRP5 gene (p.R1219H, p.H1383P, and p.T1540M) in seven patients with advanced retinopathy of prematurity, Polymorphisms in several genes involved in the Wnt signaling pathway were associated with hepatic fibrosis or inflammation risk in HCV-infected males., Defective trafficking resulting in haploinsufficiency is a major cellular mechanism for several missense FEVR-causing FZD4 mutants., analysis of allosteric ligands of Frizzled4, The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP (retinopathy of prematurity) and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth., These structural, biophysical and cellular data, map Fz4 and putative Lrp5/6 binding sites to distinct patches on Norrin, and reveal a GAG binding site spanning Norrin and Fz4 cysteine-rich domain., Mutations of FZD4 accounted for the largest proportion, which could be directly applied to the testing strategy to start with screening for FZD4 mutations., Letter, Two were novel mutations,
OMIM_DISEASE Exudative vitreoretinopathy 1, Retinopathy of prematurity,
SP_COMMENT disease:Defects in FZD4 are the cause of vitreoretinopathy exudative type 1 (EVR1) [MIM:133780]; also known as autosomal dominant familial exudative vitreoretinopathy (FEVR) or Criswick-Schepens syndrome. EVR1 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., domain:Lys-Thr-X-X-X-Trp motif is involved in the activation of the Wnt/beta-catenin signaling pathway., domain:The FZ domain is involved in binding with Wnt ligands., function:Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a critical role in retinal angiogenesis., similarity:Belongs to the G-protein coupled receptor Fz/Smo family., similarity:Contains 1 FZ (frizzled) domain., subunit:Binds NDP. Interacts with MAGI3., tissue specificity:Almost ubiquitous. Largely expressed in adult heart, skeletal muscle, ovary, and fetal kidney. Moderate amounts in adult liver, kidney, pancreas, spleen, and fetal lung, and small amounts in placenta, adult lung, prostate, testis, colon, fetal brain and liver.,