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FLASH GENE
Symbol FZD4 contributors: mct/shn - updated : 16-05-2014
HGNC name frizzled homolog 4 (Drosophila)
HGNC id 4042
Corresponding disease
EVR1 familial, exudative vitreoretinopathy 1
Location 11q14.2      Physical location : 86.656.721 - 86.666.433
Synonym name
  • frizzled (Drosophila) homolog 4
  • norrin receptor
  • exudative vitreoretinopathy 1
  • WNT receptor frizzled-4
  • exudative vitreoretinopathy 1 (autosomal dominant;
  • Criswick-Schepens syndrome)
    Synonym symbol(s) FZD4S, EVR1, CD344, FEVR, Fz-4, FzE4, GPCR, MGC34390, FZ4
    DNA
    TYPE functioning gene
    STRUCTURE 9.71 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D11S1887 - D18S864 - FZD4 - D11S896 - D11S4082 - qter
    RNA
    TRANSCRIPTS type messenger
    text FZD4S, a splicing variant of frizzled-4, encoding a soluble-type positive regulator of the WNT signaling pathway
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 7391 59.7 537 - -
    EXPRESSION
    Rna function mRNAs expressed specifically in adult spiral ganglion neurons (
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly Homo sapiens
    Digestiveintestinelarge intestinecolon lowly Homo sapiens
     liver   moderately Homo sapiens
    Endocrinepancreas   moderately Homo sapiens
    Lymphoid/Immunespleen   moderately Homo sapiens
    Nervousbrain   moderately
    Reproductivefemale systemplacenta  lowly Homo sapiens
     female systemovary  highly Homo sapiens
     male systemtestis  lowly Homo sapiens
     male systemprostate  lowly Homo sapiens
    Respiratorylung   lowly Homo sapiens
    Urinarykidney   moderately Homo sapiens
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Lymphoid    
    Muscularstriatumskeletal highly Homo sapiens
    cell lineage
    cell lines HeLa S3, K-562, SW480, G361, 766T, MIA PaCa-2 (
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text kidney, lung, brain, liver (
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal extracellular cysteine-rich (CRD) domain with a critical role in Norrin binding and activation of the beta-catenin pathway
  • a frizzled domain
  • seven transmembrane segments (7TM)
  • a C-terminal S/T-X-V motif
  • HOMOLOGY
    interspecies ortholog to Fzd4, Mus musculus
    ortholog to FZD4, Pan troglodytes
    ortholog to Fzd4, Rattus norvegicus
    intraspecies homolog to FZD9 and FZD10
    Homologene
    FAMILY
  • frizzled gene family
  • CATEGORY receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway
  • exhibiting characteristics of a WNT receptor, involved in regulation of the WNT signaling pathway
  • controles vascular development in the retina and inner ear
  • modulates apoptosis and enhances WNT3A induced beta-catenin stability in myeloid progenitor cells
  • an essential role in retinal endothelial cells
  • required for vascular integrity in the cerebellum
  • Fz4/Lrp5 signaling could play a role in vascular growth, remodeling, and maintenance in a variety of normal and pathologic contexts beyond the retina
  • plays a crucial role in vascular development in the retina
  • required for physiological and pathologic angiogenesis in the retina, for regulation of retinal endothelial cell differentiation, and for maintaining the integrity of the mature blood-retina barrier (
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • RCBTB1 participates in the NDP/FZD4 signaling pathway
  • a component
  • FZD4, LRP5, and TSPAN12 are component of the Norrin-FZD4 complex
  • instead of inducing FZD4 dimerization, NDP induces the formation of a ternary complex with FZD4 and LRP5/6 by binding to their respective extracellular domains
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NDP (norrin) receptor (signaling system playing a central role in vascular development in the eye and ear)
  • PDZ domains of PSD-95
  • activates calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway
  • membrane associated guanylate kinase, WW and PDZ domain containing 3, MAGI3
  • TSKU functions as a WNT signaling inhibitor by binding directly to the cysteine-rich domain of FZD4
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EVR1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in acute myeloid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • FZD4-/- mice exhibit a progressive cerebellar degeneration, auditory and esophageal dysfunction (Wang et al, 2001)
  • loss of Fz4 signaling in endothelial murin cells causes defective vascular growth leading to chronic but reversible silencing of retinal neurons leading to visual dfects and disrupts the blood brain barrier in the cerebellum (Ye et al, 2009)