Fzd4 frizzled class receptor 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Fzd4provided by MGI
Official Full Name: frizzled class receptor 4provided by MGI
Primary source: MGI:MGI:108520
See related: Ensembl:ENSMUSG00000049791 AllianceGenome:MGI:108520
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Fz4
Summary: Enables Wnt-activated receptor activity; Wnt-protein binding activity; and cytokine binding activity. Involved in several processes, including cell surface receptor signaling pathway involved in cell-cell signaling; regulation of transcription, DNA-templated; and vasculature development. Acts upstream of or within several processes, including cellular response to leukemia inhibitory factor; regulation of signal transduction; and vasculature development. Located in several cellular components, including cell-cell junction; dendrite; and glutamatergic synapse. Is expressed in several structures, including alimentary system; branchial arch; genitourinary system; nervous system; and sensory organ. Used to study Norrie disease and exudative vitreoretinopathy. Human ortholog(s) of this gene implicated in exudative vitreoretinopathy 1. Orthologous to human FZD4 (frizzled class receptor 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in subcutaneous fat pad adult (RPKM 32.3), genital fat pad adult (RPKM 28.0) and 16 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 D3; 7 49.32 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (89053574..89062341)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (89404366..89410110)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clematichinenoside AR inhibits the pathology of rheumatoid arthritis by blocking the circPTN/miR-145-5p/FZD4 signal axis.
Title: Clematichinenoside AR inhibits the pathology of rheumatoid arthritis by blocking the circPTN/miR-145-5p/FZD4 signal axis.
The mechanism of the WNT5A and FZD4 receptor mediated WNT/beta-catenin pathway in the degeneration of ALS spinal cord motor neurons.
Title: The mechanism of the WNT5A and FZD4 receptor mediated WNT/β-catenin pathway in the degeneration of ALS spinal cord motor neurons.
NORRIN presented to FZD4 further increases cardiomyocyte output via proliferation through the canonical WNT pathway.
Title: FZD4 Marks Lateral Plate Mesoderm and Signals with NORRIN to Increase Cardiomyocyte Induction from Pluripotent Stem Cell-Derived Cardiac Progenitors.
results provide functional and biochemical dissection of Fzd4 in Norrin signaling.
Title: Biophysical and functional characterization of Norrin signaling through Frizzled4.
FZD4 was upregulated during cyclic mechanical stretch (CMS)-induced osteogenic differentiation, and the JNK signalling pathway was activated. FZD4 knockdown inhibited the mechanical stimuli-induced osteogenesis and JNK activity.
Title: Wnt5a/FZD4 Mediates the Mechanical Stretch-Induced Osteogenic Differentiation of Bone Mesenchymal Stem Cells.
These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.
Title: Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Fzd4 and Fzd6 genes have a deep patterning effect on arterial vessel morphogenesis that may determine its functional efficiency
Title: Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesis.
Study identified a novel Wnt5a/Fzd4 signaling pathway that contributes to the regulation of dendrite morphogenesis
Title: A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4.
These results question the conclusion that a dominant-negative mechanism would explain the dominance of the mutant L501fsX533 Fz4 allele in the transmission of a form of Familial exudative vitreoretinopathy.
Title: ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum.
The data reveal both cell-autonomous and cell-nonautonomous effects, and they imply a central role for Norrin/Fz4 signaling in central nervous system vascular development and in the maintenance of the blood brain barrier/blood retina barrier state.
Title: Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (6) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Fzd4 (e-PCR), detects polymorphism
- UniSTS:506910

Fzd4 (e-PCR), detects polymorphism
- UniSTS:498741

U43317 (e-PCR)
- UniSTS:125749

Fzd4 (e-PCR), detects polymorphism
- UniSTS:516477

Fzd4 (e-PCR), detects polymorphism
- UniSTS:508388

NoName (e-PCR)
- UniSTS:548581

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IEA Inferred from Electronic Annotation more info
enables PDZ domain binding	ISO Inferred from Sequence Orthology more info
enables Wnt receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables Wnt receptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables Wnt receptor activity	ISO Inferred from Sequence Orthology more info
enables Wnt-protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables Wnt-protein binding	ISO Inferred from Sequence Orthology more info
enables amyloid-beta binding	ISO Inferred from Sequence Orthology more info
enables cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables cytokine binding	ISO Inferred from Sequence Orthology more info
enables cytokine receptor activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables signaling receptor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables signaling receptor activity	ISO Inferred from Sequence Orthology more info
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Norrin signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Norrin signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in Wnt signaling pathway, calcium modulating pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in canonical Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to leukemia inhibitory factor	IEP Inferred from Expression Pattern more info	PubMed
involved_in cerebellum vasculature morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within establishment of blood-brain barrier	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within establishment of blood-brain barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in extracellular matrix-cell signaling	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within locomotion involved in locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within luteinization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell-substrate adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell-substrate adhesion	ISO Inferred from Sequence Orthology more info
involved_in non-canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of JUN kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of dendrite morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron projection arborization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of neuron projection arborization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within progesterone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of vascular endothelial growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to hypoxia	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within retina vasculature development in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retina vasculature morphogenesis in camera-type eye	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within retina vasculature morphogenesis in camera-type eye	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within retina vasculature morphogenesis in camera-type eye	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in retina vasculature morphogenesis in camera-type eye	ISO Inferred from Sequence Orthology more info
involved_in retinal blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vasculogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	TAS Traceable Author Statement more info
is_active_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: frizzled-4

Names: frizzled homolog 4; fz-4; mFz4

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.

mRNA and Protein(s)

NM_008055.4 → NP_032081.3 frizzled-4 precursor

See identical proteins and their annotated locations for NP_032081.3

Status: VALIDATED

Source sequence(s)

AK044794, AK049945, CJ171654

Consensus CDS

CCDS21441.1

UniProtKB/Swiss-Prot

Q61088

UniProtKB/TrEMBL

Q3V1B2, Q8BKS3, Q8BLL2

Related

ENSMUSP00000049852.4, ENSMUST00000058755.5

Conserved Domains (2) summary

cd07448
Location:42 → 167

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

pfam01534
Location:210 → 509

Frizzled; Frizzled/Smoothened family membrane region

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000073.7 Reference GRCm39 C57BL/6J

Range

89053574..89062341

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036152680.1 → XP_036008573.1 frizzled-4 isoform X1

UniProtKB/TrEMBL

Q8BKU9

Conserved Domains (2) summary

cd15038
Location:105 → 405

7tmF_FZD4; class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors

cl02447
Location:1 → 63

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain