TRDMT1
Chr 10tRNA aspartic acid methyltransferase 1
Also known as: DMNT2, DNMT2, MHSAIIP, PUMET, RNMT1
This protein specifically methylates cytosine-38 in the anticodon loop of aspartic acid transfer RNA (tRNA-Asp), with higher activity on tRNA modified with queuosine. Mutations cause autosomal recessive intellectual developmental disorder with cardiac arrhythmias, which typically presents in early childhood with developmental delays and cardiac conduction abnormalities. The gene shows very high constraint against loss-of-function variants, indicating that complete loss of protein function is poorly tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
101 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 | 14 | 0 | 14 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 52 | 6 | 0 | 58 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 0 | 56 | 21 | 1 | 78 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRDMT1 · 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