FZD3
Chr 8frizzled class receptor 3
Also known as: Fz-3
The FZD3 protein is a seven-transmembrane receptor for Wnt signaling proteins that controls axon growth and guidance during development of major central nervous system fiber tracts including the corpus callosum, corticospinal tract, and thalamocortical connections, as well as peripheral motor nerves and neural tube closure. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, intellectual disability, seizures, and structural brain abnormalities including agenesis of the corpus callosum. This gene is highly intolerant to loss-of-function mutations, indicating that complete loss of protein function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FZD3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools