WDR27

Chr 6

WD repeat domain 27

This gene encodes a protein with multiple WD repeats that forms scaffolds for protein-protein interactions and plays key roles in cell signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability, seizures, and brain malformations including corpus callosum abnormalities. The gene is extremely intolerant to loss-of-function variants, indicating it is essential for normal development.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.89
Clinical SummaryWDR27
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.18
OE 0.67 (0.510.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.59Z-score
OE missense 1.07 (1.001.16)
528 obs / 491.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.510.89)
00.351.4
Missense OE1.07 (1.001.16)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 34 / 50.8Missense obs/exp: 528 / 491.2Syn Z: -0.04
DN
0.6743th %ile
GOF
0.5268th %ile
LOF
0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

WDR27 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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