WDR1

Chr 4AR

WD repeat domain 1

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

NCBI Gene: 9948 ENSG00000071127 UniProt: O75083 OMIM: 604734

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein containing 9 WD repeats. WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, mostly including a trp-asp at the C-terminal end. WD domains are involved in protein-protein interactions. The encoded protein may help induce the disassembly of actin filaments. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.221 OMIM phenotype

Clinical Summary— WDR1

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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.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 166 VUS of 588 total submissions

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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 OE?0.07 (0.03–0.22)

0≤0.351.4

Missense OE?0.72 (0.65–0.80)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 2 / 28.6Missense obs/exp: 275 / 381.3Syn Z: -2.45

This gene — mechanism propensity

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

588 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

VUS166

Likely Benign366

Benign24

Conflicting5

Pathogenic

166

VUS

366

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	8	0	0	8
Likely Pathogenic	0	0	0	0	0
VUS	5	148	9	4	166
Likely Benign	0	4	157	205	366
Benign	0	3	19	2	24
Conflicting	—				5
Total	5	163	185	211	569

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 98) ClinVar copy-number / structural variants overlap WDR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →