TRMT5
Chr 14ARtRNA methyltransferase 5
Also known as: COXPD26, KIAA1393, PNSED, TRM5
TRMT5 encodes a methyltransferase that specifically methylates guanosine-37 in various tRNAs, which is the first step in biosynthesis of wybutosine, a modified base required for accurate decoding during protein translation. Biallelic mutations cause autosomal recessive peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.588), consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
297 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 | 1 | 12 | 0 | 13 |
Likely Pathogenic | 2 | 0 | 4 | 0 | 6 |
VUS | 14 | 123 | 15 | 2 | 154 |
Likely Benign | 0 | 8 | 21 | 61 | 90 |
Benign | 0 | 4 | 7 | 3 | 14 |
Conflicting | — | 7 | |||
| Total | 16 | 136 | 59 | 66 | 284 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRMT5 · 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