TRMT10B
Chr 9tRNA methyltransferase 10B
Also known as: RG9MTD3, bA3J10.9
The protein is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 in tRNAs and is involved in protein insertion into the mitochondrial inner membrane as part of the TIM22 complex. Mutations cause microcephaly, short stature, and limb defects with autosomal recessive inheritance. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
137 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 | 62 | 0 | 62 |
Likely Pathogenic | 0 | 0 | 9 | 0 | 9 |
VUS | 0 | 45 | 4 | 0 | 49 |
Likely Benign | 1 | 4 | 0 | 1 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 49 | 75 | 1 | 126 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRMT10B · 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