WDFY3

Chr 4AD

WD repeat and FYVE domain containing 3

Also known as: ALFY, BCHS, MCPH18, ZFYVE25

NCBI Gene: 23001 ENSG00000163625 UniProt: Q8IZQ1 OMIM: 617485

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a phosphatidylinositol 3-phosphate-binding protein that functions as a master conductor for aggregate clearance by autophagy. This protein shuttles from the nuclear membrane to colocalize with aggregated proteins, where it complexes with other autophagic components to achieve macroautophagy-mediated clearance of these aggregated proteins. However, it is not necessary for starvation-induced macroautophagy. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Microcephaly 18, primary, autosomal dominantMIM #617520

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· G2P