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Aliases for FZD4 Gene

Aliases for FZD4 Gene

  • Frizzled Class Receptor 4 2 3 5
  • Frizzled 4, Seven Transmembrane Spanning Receptor 2 3
  • Frizzled Family Receptor 4 2 3
  • Fz-4 3 4
  • FzE4 3 4
  • HFz4 3 4
  • Frizzled (Drosophila) Homolog 4 2
  • Frizzled Homolog 4 (Drosophila) 2
  • Exudative Vitreoretinopathy 1 2
  • WNT Receptor Frizzled-4 3
  • Frizzled Homolog 4 3
  • CD344 Antigen 4
  • Frizzled-4 3
  • CD344 3
  • FZD4S 3
  • FEVR 3
  • GPCR 3
  • EVR1 3
  • Fz4 3

External Ids for FZD4 Gene

Previous HGNC Symbols for FZD4 Gene

  • EVR1

Previous GeneCards Identifiers for FZD4 Gene

  • GC11U990161
  • GC11M088195
  • GC11M086879
  • GC11M086383
  • GC11M086334
  • GC11M086656
  • GC11M082945

Summaries for FZD4 Gene

Entrez Gene Summary for FZD4 Gene

  • This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]

GeneCards Summary for FZD4 Gene

FZD4 (Frizzled Class Receptor 4) is a Protein Coding gene. Diseases associated with FZD4 include Exudative Vitreoretinopathy 1 and Exudative Vitreoretinopathy. Among its related pathways are Wnt Signaling Pathways: beta-Catenin-dependent Wnt Signaling and HTLV-I infection. GO annotations related to this gene include G-protein coupled receptor activity and protein heterodimerization activity. An important paralog of this gene is FZD10.

UniProtKB/Swiss-Prot for FZD4 Gene

  • Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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.

Gene Wiki entry for FZD4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FZD4 Gene

Genomics for FZD4 Gene

Regulatory Elements for FZD4 Gene

Enhancers for FZD4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11F086589 0.5 Ensembl ENCODE 13.2 +361.5 361523 8.2 HDGF PKNOX1 ARNT CREB3L1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ME3 PRSS23 CREBZF FZD4 LOC100420680 GC11P086590 PIR37636 PIR51163
GH11F086301 0.2 ENCODE 13.2 +652.9 652854 1.9 HDGF ARNT CREB3L1 ARID4B SIN3A DMAP1 YY1 SLC30A9 ZNF207 ZNF143 CREBZF PRSS23 FZD4 HIKESHI RN7SL225P
GH11F086243 0.5 ENCODE 13.2 +710.3 710338 3.7 HDGF PKNOX1 ARNT CREB3L1 WRNIP1 ZFP64 ARID4B SIN3A FEZF1 DMAP1 HIKESHI CREBZF PRSS23 FZD4 CCDC89 EED MIR6755 LOC100289518
GH11F087281 1.1 Ensembl ENCODE 9.6 -326.3 -326333 1.1 CTCF PKNOX1 ZNF654 ATF1 CEBPB ZBTB40 EP300 RAD21 RFX5 ZNF121 ENSG00000255471 FZD4 LOC101929104 LOC100420680
GH11F087254 0.2 ENCODE 8.9 -299.4 -299371 0.9 NFIL3 FZD4 GC11M087259 GC11P087232
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around FZD4 on UCSC Golden Path with GeneCards custom track

Promoters for FZD4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000320877 798 4401 HDGF PKNOX1 ZFP64 ARID4B SIN3A DMAP1 ZNF48 GLIS2 KLF13 SP3

Genomic Location for FZD4 Gene

Chromosome:
11
Start:
86,945,675 bp from pter
End:
86,955,398 bp from pter
Size:
9,724 bases
Orientation:
Minus strand

Genomic View for FZD4 Gene

Genes around FZD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FZD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FZD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FZD4 Gene

Proteins for FZD4 Gene

  • Protein details for FZD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULV1-FZD4_HUMAN
    Recommended name:
    Frizzled-4
    Protein Accession:
    Q9ULV1
    Secondary Accessions:
    • A8K9Q3
    • Q14C97
    • Q6S9E4

    Protein attributes for FZD4 Gene

    Size:
    537 amino acids
    Molecular mass:
    59881 Da
    Quaternary structure:
    • Interacts with MAGI3 and norrin (NDP). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (By similarity).

    Three dimensional structures from OCA and Proteopedia for FZD4 Gene

neXtProt entry for FZD4 Gene

Post-translational modifications for FZD4 Gene

  • Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.
  • Glycosylation at Asn 59 and Asn 144
  • Modification sites at PhosphoSitePlus

Other Protein References for FZD4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for FZD4 Gene

Domains & Families for FZD4 Gene

Protein Domains for FZD4 Gene

Suggested Antigen Peptide Sequences for FZD4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9ULV1

UniProtKB/Swiss-Prot:

FZD4_HUMAN :
  • Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
  • Belongs to the G-protein coupled receptor Fz/Smo family.
Domain:
  • Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
  • The FZ domain is involved in binding with Wnt ligands.
  • Contains 1 FZ (frizzled) domain.
Family:
  • Belongs to the G-protein coupled receptor Fz/Smo family.
genes like me logo Genes that share domains with FZD4: view

Function for FZD4 Gene

Molecular function for FZD4 Gene

GENATLAS Biochemistry:
Drosophila frizzled polarity gene homolog 4,G protein coupled receptor superfamily,exhibiting characteristics of a WNT receptor,widely expressed and predominantly in fetal kidney,adult heart,skeletal muscle and ovary
UniProtKB/Swiss-Prot Function:
Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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.

Gene Ontology (GO) - Molecular Function for FZD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004871 signal transducer activity IEA --
GO:0004888 transmembrane signaling receptor activity IEA --
GO:0004930 G-protein coupled receptor activity IEA,IBA --
GO:0005515 protein binding IPI 17955262
GO:0017147 Wnt-protein binding IEA,IBA --
genes like me logo Genes that share ontologies with FZD4: view
genes like me logo Genes that share phenotypes with FZD4: view

Human Phenotype Ontology for FZD4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FZD4 Gene

MGI Knock Outs for FZD4:

Animal Model Products

  • Taconic Biosciences Mouse Models for FZD4

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for FZD4 Gene

Localization for FZD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FZD4 Gene

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for FZD4 Gene COMPARTMENTS Subcellular localization image for FZD4 gene
Compartment Confidence
extracellular 5
plasma membrane 5
golgi apparatus 1
nucleus 1

Gene Ontology (GO) - Cellular Components for FZD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IC 17955262
GO:0005911 cell-cell junction IEA --
GO:0009986 cell surface IDA 19643732
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with FZD4: view

Pathways & Interactions for FZD4 Gene

genes like me logo Genes that share pathways with FZD4: view

SIGNOR curated interactions for FZD4 Gene

Activates:

Gene Ontology (GO) - Biological Process for FZD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001568 blood vessel development IEA --
GO:0001570 vasculogenesis IEA --
GO:0007165 signal transduction IEA --
GO:0007166 cell surface receptor signaling pathway IEA --
GO:0007186 G-protein coupled receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with FZD4: view

Drugs & Compounds for FZD4 Gene

(8) Drugs for FZD4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
calcium Nutra 0

(8) Additional Compounds for FZD4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FZD4: view

Transcripts for FZD4 Gene

mRNA/cDNA for FZD4 Gene

(1) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(148) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for FZD4 Gene

Frizzled family receptor 4:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for FZD4 Gene

No ASD Table

Relevant External Links for FZD4 Gene

GeneLoc Exon Structure for
FZD4
ECgene alternative splicing isoforms for
FZD4

Expression for FZD4 Gene

mRNA expression in normal human tissues for FZD4 Gene

mRNA differential expression in normal tissues according to GTEx for FZD4 Gene

This gene is overexpressed in Adipose - Subcutaneous (x5.9) and Adipose - Visceral (Omentum) (x5.3).

Protein differential expression in normal tissues from HIPED for FZD4 Gene

This gene is overexpressed in Urine (56.0) and Neutrophil (9.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for FZD4 Gene



Protein tissue co-expression partners for FZD4 Gene

NURSA nuclear receptor signaling pathways regulating expression of FZD4 Gene:

FZD4

SOURCE GeneReport for Unigene cluster for FZD4 Gene:

Hs.591968

mRNA Expression by UniProt/SwissProt for FZD4 Gene:

Q9ULV1-FZD4_HUMAN
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.
genes like me logo Genes that share expression patterns with FZD4: view

Primer Products

Orthologs for FZD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for FZD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FZD4 34 35
  • 99.75 (n)
dog
(Canis familiaris)
Mammalia FZD4 34 35
  • 92.74 (n)
mouse
(Mus musculus)
Mammalia Fzd4 34 16 35
  • 92.3 (n)
cow
(Bos Taurus)
Mammalia FZD4 34 35
  • 91.56 (n)
rat
(Rattus norvegicus)
Mammalia Fzd4 34
  • 91.19 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia FZD4 35
  • 90 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia FZD4 35
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves FZD4 34 35
  • 84.72 (n)
lizard
(Anolis carolinensis)
Reptilia FZD4 35
  • 94 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia fzd4 34
  • 79.48 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.460 34
zebrafish
(Danio rerio)
Actinopterygii fzd4 34 35
  • 72.35 (n)
fruit fly
(Drosophila melanogaster)
Insecta fz4 36
  • 33 (a)
fz2 35
  • 32 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea cfz-2 36
  • 34 (a)
mom-5 36
  • 34 (a)
mig-1 36
  • 31 (a)
Y34D9B.1b 36
  • 31 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 46 (a)
OneToOne
Species where no ortholog for FZD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FZD4 Gene

ENSEMBL:
Gene Tree for FZD4 (if available)
TreeFam:
Gene Tree for FZD4 (if available)

Paralogs for FZD4 Gene

Paralogs for FZD4 Gene

(10) SIMAP similar genes for FZD4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with FZD4: view

Variants for FZD4 Gene

Sequence variations from dbSNP and Humsavar for FZD4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs104894223 Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780], Pathogenic 86,951,990(-) CCATC(A/G)TATTT nc-transcript-variant, reference, missense
rs139401671 Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780] 86,954,968(+) TTCCT(C/G)GTCCC upstream-variant-2KB, reference, missense
rs80358281 Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780] 86,954,979(-) GCGGG(A/G)CTTCG upstream-variant-2KB, reference, missense
rs80358282 Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780], Likely benign 86,954,881(-) TTGGG(C/T)ACGAG upstream-variant-2KB, reference, missense
rs80358284 Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780], Pathogenic 86,952,443(-) TGCCA(A/G/T)TGTGC nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for FZD4 Gene

Variant ID Type Subtype PubMed ID
esv3627099 CNV gain 21293372

Variation tolerance for FZD4 Gene

Residual Variation Intolerance Score: 22.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.17; 51.84% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FZD4 Gene

Human Gene Mutation Database (HGMD)
FZD4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FZD4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FZD4 Gene

Disorders for FZD4 Gene

MalaCards: The human disease database

(13) MalaCards diseases for FZD4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
exudative vitreoretinopathy 1
  • retinopathy of prematurity
exudative vitreoretinopathy
  • familial exudative vitreoretinopathy
coats disease
  • coats' disease
ndp-related retinopathy of prematurity
  • retinopathy of prematurity
persistent hyperplastic primary vitreous
  • phpv
- elite association - COSMIC cancer census association via MalaCards
Search FZD4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FZD4_HUMAN
  • Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: 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. 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:12172548, ECO:0000269 PubMed:14507768, ECO:0000269 PubMed:15035989, ECO:0000269 PubMed:15223780, ECO:0000269 PubMed:15370539, ECO:0000269 PubMed:15488808, ECO:0000269 PubMed:15733276, ECO:0000269 PubMed:15981244, ECO:0000269 PubMed:17093393, ECO:0000269 PubMed:19172507, ECO:0000269 PubMed:19324841, ECO:0000269 PubMed:20340138}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for FZD4

Genetic Association Database (GAD)
FZD4
Human Genome Epidemiology (HuGE) Navigator
FZD4
Tumor Gene Database (TGDB):
FZD4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FZD4
genes like me logo Genes that share disorders with FZD4: view

No data available for Genatlas for FZD4 Gene

Publications for FZD4 Gene

  1. Severe retinopathy of prematurity associated with FZD4 mutations. (PMID: 20141357) Ells A. … Robitaille J.M. (Ophthalmic Genet. 2010) 3 4 22 46 64
  2. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. (PMID: 15981244) Qin M. … Kondo H. (Hum. Mutat. 2005) 3 4 22 46 64
  3. Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity. (PMID: 14507768) Kondo H. … Hayashi K. (Br. J. Ophthalmol. 2003) 3 4 22 46 64
  4. Molecular cloning and characterization of human frizzled-4 on chromosome 11q14-q21. (PMID: 10544037) Kirikoshi H. … Katoh M. (Biochem. Biophys. Res. Commun. 1999) 2 3 4 22 64
  5. Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with persistent fetal vasculature (PFV) caused by FZD4 mutations in two distinct pedigrees. (PMID: 19172507) Robitaille J.M. … Guernsey D.L. (Ophthalmic Genet. 2009) 3 4 22 64

Products for FZD4 Gene

Sources for FZD4 Gene

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