METTL4
Chr 18methyltransferase 4, N6-adenosine
Also known as: HsT661
METTL4 encodes a methyltransferase that adds methyl groups to adenine residues in both RNA and DNA, regulating RNA splicing through snRNA modification and controlling mitochondrial transcript levels and DNA copy number. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. This gene is not highly constrained against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
221 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 | 0 | 0 | 124 | 0 | 124 |
Likely Pathogenic | 1 | 0 | 2 | 0 | 3 |
VUS | 0 | 54 | 22 | 0 | 76 |
Likely Benign | 0 | 0 | 1 | 0 | 1 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 54 | 149 | 0 | 204 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
METTL4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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