FZD4 frizzled family receptor 4 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: FZD4provided by HGNC
Official Full Name: frizzled family receptor 4provided by HGNC
Primary source: HGNC:4042
See related: Ensembl:ENSG00000174804; HPRD:05203; MIM:604579; Vega:OTTHUMG00000167231
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: Fz4; EVR1; FEVR; Fz-4; FzE4; GPCR; hFz4; CD344; FZD4S
Summary: 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]

Genomic context

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Location :: 11q14.2

Sequence :: Chromosome: 11; NC_000011.9 (86656717..86666440, complement)

See FZD4 in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Five mutations have been found in the FZD4 gene in six Chinese families with familial exudative vitreoretinopathy.
Title: Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy.
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.
Title: Familial retinal detachment associated with COL2A1 exon 2 and FZD4 mutations.
miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4.
Title: Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4.
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.
Title: Frizzled 4 regulates stemness and invasiveness of migrating glioma cells established by serial intracranial transplantation.
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.
Title: The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease.
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.
Title: Novel frizzled-4 gene mutations in chinese patients with familial exudative vitreoretinopathy.
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.
Title: FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells.
Studies report 21 novel variants for FZD4, LRP5, and NDP.
Title: Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.
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.
Title: Severe retinopathy of prematurity associated with FZD4 mutations.
Mutations occurring in the FZD4 gene affect patients diagnosed with both autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP)
Title: Clinical presentation and genetic correlation of patients with mutations affecting the FZD4 gene.

Submit: New GeneRIF Correction See all (25)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Familial exudative vitreoretinopathy

MIM: 133780

Genetic Testing Registry

Summary from GeneReviews: Familial Exudative Vitreoretinopathy, Autosomal Dominant

Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is characterized by failure of peripheral retinal vascularization. The visual problems and variable phenotype associated with adFEVR result from secondary complications caused by retinal ischemia. The retinal avascularity is probably present from birth and generates sequelae that stabilize in early adult life or progress in later life. Expressivity may be asymmetric and is highly variable, ranging from mild or asymptomatic to severe (e.g., registered as blind) within the same family.

Diagnosis Testing

The diagnosis of adFEVR is based on a family history compatible with autosomal dominant inheritance and bilateral peripheral retinal avascularity, seen temporally, by indirect ophthalmoscope and scleral indentation, or by fundus fluorescein angiography. Mutations in one of three genes are known to be associated with adFEVR: FZD4, encoding the protein frizzled-4; LRP5, encoding low-density lipoprotein receptor-related protein 5; and TSPAN12, encoding tetraspanin-12. Mutations in these genes are responsible for fewer than 50% of adFEVR cases. Another locus, EVR3, has been mapped; the gene is not known. Molecular genetic testing for mutations in FZD4, LRP5, and TSPAN12 is available clinically.

Genetic Counseling

Autosomal dominant FEVR is inherited in an autosomal dominant manner. Offspring of an affected individual are at a 50% risk of inheriting the mutation, but many individuals with adFEVR can be asymptomatic because of reduced penetrance. Prenatal testing is available.

References

PMID: 20301326

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9ULV1	P32121	ARRB2	HPRD	PubMed
Q9ULV1	Q12959	DLG1	HPRD	PubMed
Q9ULV1	Q15700	DLG2	HPRD	PubMed
Q9ULV1	P78352	DLG4	HPRD	PubMed
Q9ULV1	O14641	DVL2	HPRD	PubMed
Q9ULV1	MAGI-3	MAGI3	HPRD	PubMed
BioGRID:113918	BioGRID:113647	BAG6	BioGRID	PubMed	Two-hybrid
BioGRID:113918	BioGRID:108086	DLG4	BioGRID	PubMed	Two-hybrid
BioGRID:113918	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:113918	BioGRID:123905	ZNRF3	BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Basal cell carcinoma, organism-specific biosystem (from KEGG)
Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Basal cell carcinoma, conserved biosystem (from KEGG)
Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
HTLV-I infection, organism-specific biosystem (from KEGG)
HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
HTLV-I infection, conserved biosystem (from KEGG)
HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
Hippo signaling pathway, organism-specific biosystem (from KEGG)
Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
Hippo signaling pathway, conserved biosystem (from KEGG)
Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
Melanogenesis, organism-specific biosystem (from KEGG)
Melanogenesis, organism-specific biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
Melanogenesis, conserved biosystem (from KEGG)
Melanogenesis, conserved biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
Proteoglycans in cancer, organism-specific biosystem (from KEGG)
Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Proteoglycans in cancer, conserved biosystem (from KEGG)
Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
Wnt Signaling Pathway NetPath, organism-specific biosystem (from WikiPathways)
Wnt Signaling Pathway NetPath, organism-specific biosystemWnt family of proteins are a large family of cysteine-rich secreted glycoproteins that regulate cell-cell interactions. They bind to members of the Frizzled family of 7 transmembrane receptors. Bindi...
Wnt Signaling Pathway and Pluripotency, organism-specific biosystem (from WikiPathways)
Wnt Signaling Pathway and Pluripotency, organism-specific biosystemThis pathway was adapted from several resources and is designed to provide a theoretical frame-work for examining Wnt signaling and interacting components in the context of embryonic stem-cell plurip...
Wnt signaling network, organism-specific biosystem (from Pathway Interaction Database)
Wnt signaling network, organism-specific biosystem
Wnt signaling network
Wnt signaling pathway, organism-specific biosystem (from KEGG)
Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
Wnt signaling pathway, conserved biosystem (from KEGG)
Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...

General gene information

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Markers

RH48350 (e-PCR)
- UniSTS:18202

FZD4 (e-PCR)
- UniSTS:279366

L18426 (e-PCR)
- UniSTS:34648

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

D11S896 (e-PCR), detects polymorphism
- UniSTS:18829

D11S3114 (e-PCR)
- UniSTS:152207

RH91382 (e-PCR)
- UniSTS:83629

G20766 (e-PCR)
- UniSTS:43186

A006F30 (e-PCR)
- UniSTS:43187

FZD4_7916 (e-PCR)
- UniSTS:468430

STS-R26141 (e-PCR)
- UniSTS:53456

Genotypes

See FZD4 SNP Geneview Report
See FZD4 SNP Genotype Report
See FZD4 SNP Variation Viewer Report

Homology

Homologs of the FZD4 gene: The FZD4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC34390

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G-protein coupled receptor activity	IEA Inferred from Electronic Annotation more info
PDZ domain binding	IDA Inferred from Direct Assay more info
PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
Wnt-activated receptor activity	IDA Inferred from Direct Assay more info	PubMed
Wnt-protein binding	IBA Inferred from Biological aspect of Ancestor more info
cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info

Process	Evidence Code	Pubs
Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Wnt receptor signaling pathway, calcium modulating pathway	IDA Inferred from Direct Assay more info	PubMed
brain development	IBA Inferred from Biological aspect of Ancestor more info
canonical Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cellular response to retinoic acid	ISS Inferred from Sequence or Structural Similarity more info
cerebellum vasculature morphogenesis	IEA Inferred from Electronic Annotation more info
embryo development	IBA Inferred from Biological aspect of Ancestor more info
extracellular matrix-cell signaling	IEA Inferred from Electronic Annotation more info
locomotion involved in locomotory behavior	IEA Inferred from Electronic Annotation more info
negative regulation of cell-substrate adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of JUN kinase activity	IEA Inferred from Electronic Annotation more info
positive regulation of sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
progesterone secretion	IBA Inferred from Biological aspect of Ancestor more info
regulation of vascular endothelial growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
retina vasculature morphogenesis in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
retinal blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
sensory perception of sound	IEA Inferred from Electronic Annotation more info
substrate adhesion-dependent cell spreading	IBA Inferred from Biological aspect of Ancestor more info
vasculogenesis	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
cell projection	IBA Inferred from Biological aspect of Ancestor more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
cell-cell junction	IEA Inferred from Electronic Annotation more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
integral to plasma membrane	IC Inferred by Curator more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: frizzled-4

Names: frizzled-4; frizzled homolog 4; WNT receptor frizzled-4; frizzled 4, seven transmembrane spanning receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011752.1 RefSeqGene

Range

4994..14717

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_012193.3 → NP_036325.2 frizzled-4 precursor

Status: REVIEWED

Source sequence(s)

AK292768, AP001528, BC114527

Consensus CDS

CCDS8279.1

UniProtKB/Swiss-Prot

Q9ULV1

Related

ENSP00000434034, OTTHUMP00000235516, ENST00000531380, OTTHUMT00000393818

Conserved Domains (2) summary

cd07448
Location:42 – 167
Blast Score: 706

CRD_FZ4; Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor.

pfam01534
Location:210 – 514
Blast Score: 1269

Frizzled; Frizzled/Smoothened family membrane region

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p10 Primary Assembly

Range

86656717..86666440, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

82945786..82952580, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018922.1 Alternate CHM1_1.0

Range

86524637..86534357, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB083613.1	BAB89326.1
genomic	ABBA01017318.1 (2231..9025)	None
genomic	AMYH01003851.1 (835391..845111)	None
genomic	AP001528.4 (64188..73904)	None
genomic	CH471076.1	EAW75147.1
mRNA	AB032417.1	BAA86286.1
mRNA	AB054881.1	BAB40811.1
mRNA	AK025516.1	None
mRNA	AK025791.1	None
mRNA	AK292768.1	BAF85457.1
mRNA	AY462097.1	AAR23924.1
mRNA	BC025750.1	None
mRNA	BC114527.1	AAI14528.1
mRNA	BC114622.1	AAI14623.1