MARS2
Chr 2ARmethionyl-tRNA synthetase 2, mitochondrial
Also known as: COXPD25, MetRS, mtMetRS
The MARS2 protein is a mitochondrial methionyl-tRNA synthetase that charges tRNA with methionine for mitochondrial protein synthesis. Mutations cause autosomal recessive spastic ataxia-3 (SPAX3), a neurodegenerative disorder, and combined oxidative phosphorylation deficiency 25. The gene shows low constraint against loss-of-function variants (pLI ~0), making homozygous or compound heterozygous mutations the likely disease mechanism in this autosomal recessive condition.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MARS2 · 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