FGD3
Chr 9FYVE, RhoGEF and PH domain containing 3
Also known as: ZFYVE5
The FGD3 protein functions as a guanyl-nucleotide exchange factor that activates CDC42 by exchanging GDP for GTP, thereby promoting filopodium formation and regulating actin cytoskeleton organization and cell shape. Gain-of-function mutations in FGD3 cause disease, though the specific neurological phenotypes are not detailed in the available data. The extremely low pLI score (0.0000013) indicates this gene is highly tolerant to loss-of-function variants, consistent with the gain-of-function disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
FGD3 · 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