WDR1

Chr 4AR

WD repeat domain 1

Also known as: AIP1, HEL-S-52, NORI-1, PFITS

NCBI Gene: 9948ENSG00000071127UniProt: O75083

WDR1 encodes a protein that induces disassembly of actin filaments and is essential for cellular processes including cytokinesis, cell migration, and maintenance of cytoskeletal organization. Mutations cause periodic fever, immunodeficiency, and thrombocytopenia syndrome with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Periodic fever, immunodeficiency, and thrombocytopenia syndromeMIM #150550
AR
0
Active trials
9
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.22
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— WDR1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 168 VUS of 598 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.22LOEUF
pLI 0.999
Z-score 4.61
OE 0.07 (0.03–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.93Z-score
OE missense 0.72 (0.65–0.80)
275 obs / 381.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.03–0.22)
0≤0.351.4
Missense OE0.72 (0.65–0.80)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 2 / 28.6Missense obs/exp: 275 / 381.3Syn Z: -2.45
DN
0.2698th %ile
GOF
0.3094th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

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

598 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS168
Likely Benign358
Benign23
Conflicting5
23
Pathogenic
2
Likely Pathogenic
168
VUS
358
Likely Benign
23
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
4
142
18
4
168
Likely Benign
0
2
154
202
358
Benign
0
2
19
2
23
Conflicting
—5
Total4146216208579

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR1 · 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

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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients