TRMU Gene: tRNA 5-Methylaminomethyl-2-Thiouridylate Methyltransferase
Mitochondrial tRNA Modification and Deafness-Dystonia Syndrome
Gene Information Card
| Symbol | TRMU |
|---|---|
| Full Name | tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.31 |
| NCBI Gene ID | 55687 ncbi.nlm.nih.gov/gene/55687 |
| Ensembl ID | ENSG00000100413 |
| UniProt ID | O75648 |
| OMIM ID | 610230 |
| HGNC ID | 25481 |
| Aliases | MTU1, TRMT1, TRMU1 |
Description
TRMU encodes a mitochondrial tRNA-specific 2-thiouridylase that catalyzes the 2-thiolation of the 5-methylaminomethyl-2-thiouridine (mnm5s2U) modification at the wobble position of mitochondrial tRNAs for Lys, Glu, and Gln. This modification is essential for accurate codon-anticodon pairing and efficient mitochondrial translation. Loss-of-function mutations in TRMU impair mitochondrial protein synthesis, leading to tissue-specific energy deficiency, particularly in high-energy-demand tissues such as the cochlea and brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Deafness-dystonia syndrome (infantile mitochondrial DNA depletion syndrome-6, MTDPS6) | Biallelic loss-of-function mutations reduce tRNA thiolation, causing mitochondrial translation defects and ATP depletion in auditory and neural tissues. | OMIM #610230; ClinVar |
| Acute infantile liver failure due to TRMU deficiency | Mutations impair mitochondrial translation in hepatocytes, leading to transient liver failure often triggered by infection or stress. | OMIM #613070; ClinVar |
| Sensorineural hearing loss | Hypomorphic variants reduce tRNA modification efficiency, predisposing to progressive hearing loss. | ClinVar; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Heart | 6.7 | Low |
| Brain | 5.1 | Low |
| Cochlea (inner ear) | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.1 | Highest expression among tested lines |
| HEK293 (embryonic kidney) | 9.8 | Moderate |
| SH-SY5Y (neuroblastoma) | 6.3 | Low |
| K562 (leukemia) | 5.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.835G>A (p.Gly279Arg) | Missense | Rare | Loss of function; reduced tRNA thiolation; associated with deafness-dystonia |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein; infantile liver failure |
| c.424C>T (p.Arg142*) | Nonsense | Rare | Premature truncation; loss of catalytic activity |
| c.622G>A (p.Gly208Ser) | Missense | Rare | Impaired dimerization and reduced enzyme activity |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations are loss-of-function, reducing or abolishing tRNA thiolation activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • tRNA thiouridine synthesis | • tRNA wobble base modification |
| • mitochondrial translation | • tRNA binding |
| • transferase activity | • transferring sulfur-containing groups |
| • mitochondrion |
Pathways
• Mitochondrial tRNA modification
• Mitochondrial translation elongation
Protein Summary
TRMU is a 421-amino acid mitochondrial protein that functions as a homodimer. It catalyzes the 2-thiolation of the wobble uridine in mitochondrial tRNAs for Lys, Glu, and Gln, using cysteine as the sulfur donor. This modification is critical for decoding A-ending codons and maintaining mitochondrial translation fidelity. The protein contains a conserved N-terminal mitochondrial targeting sequence and a catalytic domain with a PP-loop motif. Defects in TRMU lead to mitochondrial dysfunction and tissue-specific disease phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRMU Knockout HEK293 Cell Line | EDJ-KQ15947 | Human | 55687 | Details Get a Quote |
| TRMU Knockout A-549 Cell Line | EDJ-KQ46971 | Human | 55687 | Details Get a Quote |
| TRMU Knockout HCT 116 Cell Line | EDJ-KQ46972 | Human | 55687 | Details Get a Quote |
| TRMU Knockout HeLa Cell Line | EDJ-KQ46973 | Human | 55687 | Details Get a Quote |
