WDR26

Chr 1

WD repeat domain 26

Also known as: CDW2, GID7, MIP2, SKDEAS

NCBI Gene: 80232ENSG00000162923UniProt: Q9H7D7

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]

Primary Disease Associations & Inheritance

UniProtSkraban-Deardorff syndrome
302
ClinVar variants
97
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— WDR26
🧬
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.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 160 VUS of 302 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.47 (0.41–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 0 / 35.0Missense obs/exp: 169 / 360.5Syn Z: 1.38

ClinVar Variant Classifications

302 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic20
VUS160
Likely Benign29
Benign10
Conflicting6
77
Pathogenic
20
Likely Pathogenic
160
VUS
29
Likely Benign
10
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
2
46
0
77
Likely Pathogenic
5
11
4
0
20
VUS
1
139
19
1
160
Likely Benign
0
9
5
15
29
Benign
0
1
5
4
10
Conflicting
—6
Total351627920302

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.

Gene2Phenotype Curations

WDR26-related intellectual disability, seizures, abnormal gait, and distinctive facial features

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — WDR26
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
WDR26-related Skraban-Deardorff syndrome: clinical, genetic and pathomechanistic insights.
Lin X et al.·Eur J Med Res
2025Case report
WDR26 depletion alters chromatin accessibility and gene expression profiles in mammalian cells.
Onea G et al.·Genomics
2025
Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review.
Pavinato L et al.·Am J Med Genet A
2021Case report
WDR26 and MTF2 are therapeutic targets in multiple myeloma.
Sun F et al.·J Hematol Oncol
2021
WDR26 Haploinsufficiency Causes a Recognizable Syndrome of Intellectual Disability, Seizures, Abnormal Gait, and Distinctive Facial Features.
Skraban CM et al.·Am J Hum Genet
2017
Two Novel Variants of WDR26 in Chinese Patients with Intellectual Disability.
Hu J et al.·Genes (Basel)
2022Case report
FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability.
Schneider AL et al.·Epilepsia
2021
Skraban-Deardorff syndrome: Six new cases of WDR26-related disease and expansion of the clinical phenotype.
Cospain A et al.·Clin Genet
2021Case report
Phenotypic features of 1q41q42 microdeletion including WDR26 and FBXO28 are clinically recognizable: The first case from Japan.
Yanagishita T et al.·Brain Dev
2019Case report
Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.
Córdova-Palomera A et al.·Transl Psychiatry
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AsthmaAtherosclerosisMetabolic Syndrome

Study of the Effect of Innate on the Inflammatory Response to Endotoxin

RECRUITING
NCT01143480National Institute of Environmental Health Sciences (NIEHS)Started 2012-07-30

External Resources

Links to major genomics databases and tools