WDR26

Chr 1AD

WD repeat domain 26

Also known as: CDW2, GID7, MIP2, SKDEAS

NCBI Gene: 80232 ENSG00000162923 UniProt: Q9H7D7 OMIM: 617424

The protein is a WD repeat-containing protein that facilitates formation of multiprotein complexes involved in cell cycle progression, signal transduction, apoptosis, and gene regulation. Loss-of-function mutations cause Skraban-Deardorff syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variation, consistent with haploinsufficiency as the disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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. Two transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.091 OMIM phenotype

Clinical Summary— WDR26

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Gene-Disease Validity (ClinGen)

Skraban-Deardorff syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

62 unique Pathogenic / Likely Pathogenic· 158 VUS of 286 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — WDR26

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 5.48

OE 0.00 (0.00–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.58Z-score

OE missense 0.47 (0.41–0.53)

169 obs / 360.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.47 (0.41–0.53)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 0 / 35.0Missense obs/exp: 169 / 360.5Syn Z: 1.38

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveWDR26-related intellectual disability, seizures, abnormal gait, and distinctive facial featuresLOFAD

This gene — mechanism propensity

0.2598th %ile

GOF

0.3590th %ile

LOF

0.83top 5%

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

LOFprediction above median · 1 literature citation · 76% of P/LP variants are LoF · LOEUF 0.09 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFWDR26 haploinsufficiency causes a recognizable syndrome of intellectual disability, seizures, abnormal gait, and distinctive facial features.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 28686853 ↗

ClinVar Variant Classifications

286 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42

Likely Pathogenic20

VUS158

Likely Benign33

Benign9

Conflicting7

Pathogenic

Likely Pathogenic

158

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	39	2	1	0	42
Likely Pathogenic	8	12	0	0	20
VUS	1	147	9	1	158
Likely Benign	0	13	2	18	33
Benign	0	3	2	4	9
Conflicting	—				7
Total	48	177	14	23	269

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap WDR26 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →