WDR4
Chr 21ARWDR4 tRNA N7-guanosine methyltransferase non-catalytic subunit
Also known as: GAMOS6, MIGSB, TRM82, TRMT82, Wuho, hWH
WDR4 encodes a non-catalytic component of the METTL1-WDR4 methyltransferase complex that acts as a scaffold for tRNA binding and is required for N(7)-methylguanine formation in tRNAs, mRNAs, and microRNAs. Mutations cause autosomal recessive Galloway-Mowat syndrome 6 and a distinct phenotype of microcephaly, growth deficiency, seizures, and brain malformations. The gene is highly constrained against loss-of-function variants (LOEUF 1.116), consistent with severe developmental phenotypes when disrupted.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
455 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 5 | 1 | 87 | 0 | 93 |
Likely Pathogenic | 4 | 4 | 4 | 0 | 12 |
VUS | 2 | 127 | 19 | 0 | 148 |
Likely Benign | 2 | 13 | 49 | 72 | 136 |
Benign | 0 | 3 | 29 | 6 | 38 |
Conflicting | — | 7 | |||
| Total | 13 | 148 | 188 | 78 | 434 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
WDR4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools