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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FZD3
frizzled class receptor 3
Chromosome 8 · 8p21.1
NCBI Gene: 7976Ensembl: ENSG00000104290.12HGNC: HGNC:4041UniProt: Q9NPG1
56PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
canonical Wnt signaling pathwayplasma membraneprotein bindingcytoplasmneurodegenerative diseasecolorectal canceramyotrophic lateral sclerosisHydrocephalus
✦AI Summary

FZD3 (frizzled class receptor 3) is a seven-transmembrane G-protein coupled receptor located on chromosome 8 that functions as a Wnt signaling receptor with critical roles in neural development and cancer biology 1. The receptor transduces signals through both canonical Wnt/β-catenin pathways and non-canonical planar cell polarity (PCP) pathways; activation by Wnt ligands (e.g., Wnt5A, Wnt5B) recruits and phosphorylates disheveled proteins at the membrane, leading to either GSK-3 inhibition and nuclear β-catenin accumulation or activation of downstream effectors including RAC1 and JNK 23. FZD3 is essential for neurodevelopmental processes, controlling axon guidance and growth in major central and peripheral nervous system tracts, including the corpus callosum, corticospinal tract, and cranial motor nerves, while also regulating neural crest cell migration and inner ear sensory cell polarity 4. In melanoma, FZD3 promotes tumorigenesis independently of canonical Wnt signaling by activating MAPK pathways through a positive-feedback mechanism; elevated FZD3 mRNA correlates with metastatic progression and poor patient survival 5. Similarly, WNT5B-FZD3 signaling promotes non-small cell lung cancer malignancy via the PCP-JNK pathway 3. Genetic association studies initially suggested FZD3 polymorphisms might contribute to schizophrenia risk, but meta-analyses provide weak and inconsistent evidence, with effects potentially limited to specific populations 67.

Sources cited
1
FZD3 is a 7-transmembrane receptor located on chromosome 8p21 with higher expression in CNS and urogenital tissues
PMID: 10873558
2
FZD3 controls development of longitudinal tracts in CNS and axon navigation in peripheral, sympathetic, and enteric nervous systems
PMID: 25813877
3
FZD3 promotes melanoma tumorigenesis through MAPK signaling independently of canonical Wnt/β-catenin pathway; high FZD3 correlates with metastasis and poor survival
PMID: 30792348
4
FZD3 structures reveal Wnt5a binding at the cysteine-rich domain and DVL/G-protein binding sites at the cytoplasmic region
PMID: 39174501
5
WNT5B activates FZD3-DVL3-RAC1-PCP-JNK signaling pathway in NSCLC to promote malignant phenotype
PMID: 39094673
6
FZD3 polymorphisms show potentially weaker and population-limited effects on schizophrenia, mainly in Chinese populations
PMID: 27755292
7
Meta-analysis of FZD3 SNP markers does not support association between FZD3 and schizophrenia across diverse populations
PMID: 16707163
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.34Weak
colorectal cancerOpen Targets
0.34Weak
amyotrophic lateral sclerosisOpen Targets
0.28Weak
HydrocephalusOpen Targets
0.26Weak
Agenesis of corpus callosumOpen Targets
0.26Weak
arthrogryposis multiplex congenitaOpen Targets
0.26Weak
isolated cerebellar hypoplasia/agenesisOpen Targets
0.26Weak
multicystic dysplastic kidneyOpen Targets
0.26Weak
Abruptio PlacentaeOpen Targets
0.26Weak
cervical carcinomaOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
schizophreniaOpen Targets
0.04Suggestive
laryngeal squamous cell carcinomaOpen Targets
0.04Suggestive
leukoencephalopathy with vanishing white matter 5Open Targets
0.04Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.04Suggestive
ciliary dyskinesia, primary, 47, and lissencephalyOpen Targets
0.03Suggestive
Pathogenic Variants2
NM_017412.4(FZD3):c.1616dup (p.Asp539fs)Likely pathogenic
Corpus callosum, agenesis of;Hydrocephalus;Arthrogryposis multiplex congenita;Multicystic kidney dysplasia|Congenital cerebellar hypoplasia
☆☆☆☆2019→ Residue 539
NM_017412.4(FZD3):c.888del (p.Phe296fs)Pathogenic
Colorectal cancer
☆☆☆☆→ Residue 296
View on ClinVar ↗
Related Genes
VANGL2Protein interaction99%PRICKLE1Protein interaction98%DAAM1Protein interaction98%PARD6AProtein interaction96%BAMBIProtein interaction93%ZNRF3Protein interaction93%
Tissue Expression6 tissues
Brain
100%
Ovary
69%
Bone Marrow
28%
Heart
16%
Lung
7%
Liver
6%
Gene Interaction Network
Click a node to explore
FZD3VANGL2PRICKLE1DAAM1PARD6ABAMBIZNRF3
PROTEIN STRUCTURE
Preparing viewer…
PDB8Q7O · 1.76 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.32 [0.21–0.51]
RankingsWhere FZD3 stands among ~20K protein-coding genes
  • #8,072of 20,598
    Most Researched56
  • #4,416of 5,498
    Most Pathogenic Variants2
  • #3,146of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedFZD3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A meta-analysis of FZD3 gene polymorphisms and their association with schizophrenia.
PMID: 27755292
Psychiatr Genet · 2016
1.00
2
Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis.
PMID: 16707163
Psychiatry Res · 2006
0.90
3
Celsr3 and Fzd3 in axon guidance.
PMID: 25813877
Int J Biochem Cell Biol · 2015
0.80
4
Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling.
PMID: 30792348
Proc Natl Acad Sci U S A · 2019
0.70
5
Identification, gene structure, and expression of human frizzled-3 (FZD3).
PMID: 10873558
Biochem Biophys Res Commun · 2000
0.60