WDFY2

Chr 13

WD repeat and FYVE domain containing 2

Also known as: PROF, WDF2, ZFYVE22

The protein functions as an adapter that facilitates kinase-substrate interactions, particularly mediating PRKCZ phosphorylation of VAMP2, regulating AKT signaling pathways involved in glucose metabolism, and participating in transferrin receptor endocytosis. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia. This gene shows no constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.99
Clinical SummaryWDFY2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 67 VUS of 145 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.65 (0.440.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.04Z-score
OE missense 0.81 (0.720.91)
191 obs / 235.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.440.99)
00.351.4
Missense OE0.81 (0.720.91)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 16 / 24.4Missense obs/exp: 191 / 235.8Syn Z: -0.66

ClinVar Variant Classifications

145 submitted variants in ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic3
VUS67
Benign1
56
Pathogenic
3
Likely Pathogenic
67
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
3
0
3
VUS
0
53
14
0
67
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Total053740127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

WDFY2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗