WDR11

Chr 10ADAR

WD repeat domain 11

Also known as: BRWD2, DR11, HH14, SRI1, WDR15

NCBI Gene: 55717 ENSG00000120008 UniProt: Q9BZH6 OMIM: 606417

This protein is essential for ciliogenesis and regulates Hedgehog signaling pathway components, including GLI3 processing and gonadotropin-releasing hormone production. Mutations cause hypogonadotropic hypogonadism with or without anosmia and autosomal recessive intellectual developmental disorder. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is highly constrained against loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAD/ARLOEUF 0.532 OMIM phenotypes

Clinical Summary— WDR11

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

18 unique Pathogenic / Likely Pathogenic· 240 VUS of 534 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — WDR11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.000

Z-score 4.70

OE 0.38 (0.28–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.80Z-score

OE missense 0.80 (0.75–0.86)

528 obs / 657.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.28–0.53)

0≤0.351.4

Missense OE?0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 26 / 67.8Missense obs/exp: 528 / 657.6Syn Z: 1.17

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongWDR11-related intellectual disability and microcephalyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5477th %ile

GOF

0.3986th %ile

LOF

0.4627th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFTreatment with the Hh agonist purmorphamine partially rescues the WDR11 haploinsufficiency phenotypes.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 29263200 ↗

ClinVar Variant Classifications

534 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic11

VUS240

Likely Benign129

Benign137

Conflicting8

Pathogenic

Likely Pathogenic

240

VUS

129

Likely Benign

137

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	1	0	0	7
Likely Pathogenic	11	0	0	0	11
VUS	8	226	3	3	240
Likely Benign	0	7	71	51	129
Benign	0	0	126	11	137
Conflicting	—				8
Total	25	234	200	65	532

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap WDR11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →