TRMT61A: tRNA Methyltransferase 61A
A key enzyme in tRNA methylation, specifically catalyzing the formation of 1-methyladenosine at position 58 (m1A58) in tRNAs, with implications in translation regulation and cancer.
Gene Information Card
| Symbol | TRMT61A |
|---|---|
| Full Name | tRNA methyltransferase 61A |
| Gene Type | protein-coding |
| Chromosomal Location | 14q32.13 |
| NCBI Gene ID | 115708 ncbi.nlm.nih.gov/gene/115708 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q96FX7 |
| OMIM ID | 611260 |
| HGNC ID | 26037 |
| Aliases | GCD14, TRM61, TRM61A, MGC13170 |
Description
TRMT61A encodes a tRNA methyltransferase that catalyzes the formation of 1-methyladenosine at position 58 (m1A58) in tRNAs. This modification is critical for tRNA stability, folding, and translation fidelity. The protein forms a heterodimer with TRMT6 (also known as TRM61B) to function as the catalytic subunit. TRMT61A is conserved across eukaryotes and is involved in cellular stress responses and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Altered tRNA methylation affects translation of oncogenes/tumor suppressors | COSMIC; literature |
| Colorectal cancer | Upregulation of TRMT61A promotes proliferation via enhanced translation | PubMed; COSMIC |
| Breast cancer | Overexpression linked to poor prognosis and altered tRNA modification | PubMed; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Lymph node | 7.1 | Low |
| Brain | 5.2 | Low |
| Liver | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney; high expression |
| HeLa | 9.5 | Cervical cancer; moderate |
| K562 | 7.8 | Leukemia; moderate |
| HepG2 | 6.1 | Liver cancer; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.374C>T (p.Thr125Met) | Missense | <0.01% | Unknown; likely benign |
| c.487G>A (p.Gly163Arg) | Missense | <0.01% | Unknown; possibly damaging |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) likely abolish protein expression.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • tRNA methyltransferase activity | • 1-methyladenosine methyltransferase activity |
| • tRNA processing | • tRNA modification |
| • nucleus | • cytoplasm |
Pathways
• tRNA modification in the nucleus and cytoplasm
Protein Summary
TRMT61A is a 305-amino acid protein (34 kDa) that localizes to the nucleus and cytoplasm. It contains a conserved methyltransferase domain and interacts with TRMT6 to form the active m1A58 methyltransferase complex. The enzyme uses S-adenosylmethionine (SAM) as a methyl donor. Structural studies show a Rossmann-fold domain typical of Class I methyltransferases.
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