AARS2
Chr 6ARalanyl-tRNA synthetase 2, mitochondrial
Also known as: AARSL, COXPD8, LKENP, MT-ALARS, MTALARS
The encoded protein is a mitochondrial aminoacyl-tRNA synthetase that charges tRNAs with alanine during mitochondrial protein synthesis. Mutations cause combined oxidative phosphorylation deficiency 8 and progressive leukoencephalopathy with ovarian failure through autosomal recessive inheritance. The pathogenic mechanism involves impaired mitochondrial translation leading to defective oxidative phosphorylation.
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 (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
AARS2 · 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