WDFY3
Chr 4ADWD repeat and FYVE domain containing 3
Also known as: ALFY, BCHS, MCPH18, ZFYVE25
The protein encoded by this gene binds phosphatidylinositol 3-phosphate and functions as an adapter protein that links aggregated proteins to the autophagy machinery for selective clearance, playing an essential role in brain development including formation of axonal tracts and major forebrain commissures. Mutations cause primary microcephaly 18 with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants (pLI = 1, LOEUF = 0.071), consistent with its essential role in early brain development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
119 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 0 | 14 | 0 | 17 |
Likely Pathogenic | 2 | 1 | 0 | 0 | 3 |
VUS | 3 | 81 | 3 | 1 | 88 |
Likely Benign | 0 | 8 | 0 | 0 | 8 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 3 | |||
| Total | 8 | 90 | 17 | 1 | 119 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
WDFY3 · 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
External Resources
Links to major genomics databases and tools