WDFY2

Chr 13

WD repeat and FYVE domain containing 2

Also known as: PROF, WDF2, ZFYVE22

NCBI Gene: 115825 ENSG00000139668 UniProt: Q96P53

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein that contains two WD domains and an FYVE zinc finger region. The function of this gene is unknown. An alternatively spliced transcript variant of this gene may exist. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.58

OE 0.65 (0.44–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.04Z-score

OE missense 0.81 (0.72–0.91)

191 obs / 235.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.44–0.99)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 16 / 24.4Missense obs/exp: 191 / 235.8Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in WDFY2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

481 rare PASS variants

Rare truncating (LoF)

1 in 2,300

93 rare PASS variants

Rare synonymous (reference)

1 in 220

194 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for WDFY2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 4,300
South Asian	~43k	1 in 81	1 in 500
Remaining (unassigned)	~30k	1 in 110	≈ 1 in 7,500
European (Finnish)	~27k	1 in 720	1 in 2,700
Admixed American	~22k	1 in 150	1 in 2,200
African / African American	~21k	1 in 110	1 in 1,200
East Asian	~20k	1 in 200	1 in 1,700
Ashkenazi Jewish	~13k	1 in 930	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 11 marginal. Genomes: all 12.? see exons ↓