WDR26

Chr 1AD

WD repeat domain 26

Also known as: CDW2, GID7, MIP2, SKDEAS

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.091 OMIM phenotype
Clinical SummaryWDR26
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Gene-Disease Validity (ClinGen)
Skraban-Deardorff syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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
76 unique Pathogenic / Likely Pathogenic· 156 VUS of 299 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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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

Dual constrained — LoF & missense intolerant
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 5.48
OE 0.00 (0.000.09)
Highly constrained

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

Missense Constraint
3.58Z-score
OE missense 0.47 (0.410.53)
169 obs / 360.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.09)
00.351.4
Missense OE0.47 (0.410.53)
00.61.4
Synonymous OE0.85
01.21.6
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
DN
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 · 55% of P/LP variants are LoF · LOEUF 0.09

Literature Evidence

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

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

299 submitted variants in ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic19
VUS156
Likely Benign33
Benign9
Conflicting7
57
Pathogenic
19
Likely Pathogenic
156
VUS
33
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
0
22
0
57
Likely Pathogenic
7
12
0
0
19
VUS
1
142
12
1
156
Likely Benign
0
13
2
18
33
Benign
0
3
2
4
9
Conflicting
7
Total431703823281

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR26 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC