WDR62

Chr 19AR

WD repeat domain 62

Also known as: C19orf14, MCPH2

NCBI Gene: 284403ENSG00000075702UniProt: O43379

This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

Microcephaly 2, primary, autosomal recessive, with or without cortical malformationsMIM #604317
AR
1182
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— WDR62
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 268 VUS of 1182 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.86LOEUF
pLI 0.000
Z-score 2.53
OE 0.67 (0.53–0.86)
Tolerant

Typical tolerance to LoF variation

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.
0.67Z-score
OE missense 0.94 (0.88–0.99)
803 obs / 858.0 exp
Tolerant

Mild missense constraint

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.0.67 (0.53–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.88–0.99)
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.1.03
0≤1.21.6
LoF obs/exp: 47 / 69.8Missense obs/exp: 803 / 858.0Syn Z: -0.42

ClinVar Variant Classifications

1182 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic31
VUS268
Likely Benign122
Benign13
Conflicting17
27
Pathogenic
31
Likely Pathogenic
268
VUS
122
Likely Benign
13
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
1
13
0
27
Likely Pathogenic
23
2
6
0
31
VUS
3
242
20
3
268
Likely Benign
0
7
52
63
122
Benign
0
0
13
0
13
Conflicting
—17
Total3925210466478

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR62 · protein map & ClinVar variants

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

Gene2Phenotype Curations

WDR62-related microcephaly, cortical malformations, and intellectual developmental disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Microcephaly 2, primary, autosomal recessive, with or without cortical malformations

MIM #604317

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
WDR62 affects the progression of ovarian cancer by regulating the cell cycle.
Yang Y et al.·Hereditas
2025
WDR62 variants contribute to congenital heart disease by inhibiting cardiomyocyte proliferation.
Hao L et al.·Clin Transl Med
2022
Novel phenotype and genotype spectrum of WDR62 in two patients with associated primary autosomal recessive microcephaly.
Aryan H et al.·Ir J Med Sci
2022Case report
Molecular genetics, neuroimaging outcomes, and structural analyses of novel and recurrent variants of WDR62 gene in two consanguineous Pakistani families with autosomal recessive primary microcephaly.
Aslam K et al.·Mol Biol Rep
2024
Tumor‑suppressive microRNA‑223 targets WDR62 directly in bladder cancer.
Sugita S et al.·Int J Oncol
2019
Further Delineation of Phenotype and Genotype of Primary Microcephaly Syndrome with Cortical Malformations Associated with Mutations in the WDR62 Gene.
Slezak R et al.·Genes (Basel)
2021Case report
Clinical and genetic analyses in syndromic intellectual disability with primary microcephaly reveal biallelic and de novo variants in patients with parental consanguinity.
Mercan S et al.·Genes Genomics
2023Cohort
Molecular genetics of human primary microcephaly: an overview.
Faheem M et al.·BMC Med Genomics
2015Review
A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability.
Nardello R et al.·Brain Dev
2018
Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly.
Friocourt G et al.·Acta Neuropathol
2011Review
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools