MARS2: Mitochondrial Methionyl-tRNA Synthetase 2
A nuclear-encoded mitochondrial enzyme essential for protein synthesis and linked to neurodegenerative disorders.
Gene Information Card
| Symbol | MARS2 |
|---|---|
| Full Name | Methionyl-tRNA Synthetase 2, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 92935 ncbi.nlm.nih.gov/gene/92935 |
| Ensembl ID | ENSG00000147677 |
| UniProt ID | Q96GW9 |
| OMIM ID | 609355 |
| HGNC ID | 25133 |
| Aliases | MetRS, mtMetRS, MTRNS, COXPD25 |
Description
MARS2 encodes the mitochondrial methionyl-tRNA synthetase, an enzyme that catalyzes the attachment of methionine to its cognate mitochondrial tRNA (tRNAMet). This aminoacylation reaction is essential for mitochondrial translation and oxidative phosphorylation. Mutations in MARS2 have been associated with combined oxidative phosphorylation deficiency and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined oxidative phosphorylation deficiency 25 (COXPD25) | Loss-of-function mutations impair mitochondrial methionyl-tRNA charging, leading to defective mitochondrial protein synthesis and respiratory chain deficiency. | OMIM #616430; ClinVar |
| Spastic ataxia 3 (SPAX3) | Missense and splice-site variants reduce enzyme activity, causing mitochondrial dysfunction in cerebellar and spinal cord neurons. | OMIM #611390; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Brain - cerebellum | 8.2 | Low |
| Skeletal muscle | 7.1 | Low |
| Kidney | 6.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| K-562 | 9.1 | Chronic myeloid leukemia cell line |
| SH-SY5Y | 6.5 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1066G>A (p.Gly356Arg) | Missense | Rare | Reduced catalytic activity; associated with COXPD25 |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of translation initiation; associated with SPAX3 |
| c.472C>T (p.Arg158Trp) | Missense | Rare | Impaired tRNA binding; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic MARS2 mutations reduce or abolish methionyl-tRNA synthetase activity, leading to mitochondrial translation defects.
Gain of Function (GOF)
No evidence of gain-of-function mutations in MARS2.
Dominant Negative (DN)
Not reported; inheritance pattern is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • methionyl-tRNA aminoacylation | • mitochondrial translation |
| • tRNA binding | • methionine-tRNA ligase activity |
| • mitochondrion |
Pathways
• Mitochondrial tRNA aminoacylation
• Mitochondrial translation elongation
Protein Summary
MARS2 is a 593-amino-acid mitochondrial matrix protein that belongs to the class I aminoacyl-tRNA synthetase family. It contains a catalytic domain responsible for ATP-dependent methionine activation and transfer to tRNAMet. The protein is imported into mitochondria via an N-terminal mitochondrial targeting sequence. Defects in MARS2 disrupt mitochondrial protein synthesis, leading to respiratory chain deficiencies and clinical phenotypes ranging from spastic ataxia to combined oxidative phosphorylation deficiency.
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