AARS2 Gene
Alanyl-tRNA Synthetase 2, Mitochondrial
Gene Information Card
| Symbol | AARS2 |
|---|---|
| Full Name | Alanyl-tRNA Synthetase 2, Mitochondrial |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 57505 ncbi.nlm.nih.gov/gene/57505 |
| Ensembl ID | ENSG00000124608 |
| UniProt ID | Q5JTZ9 |
| OMIM ID | 612035 |
| HGNC ID | 21022 |
| Aliases | FLJ10534, FLJ20435, MGC138499 |
Description
The AARS2 gene encodes the mitochondrial alanyl-tRNA synthetase, an enzyme responsible for charging mitochondrial tRNA(Ala) with alanine. This protein is essential for mitochondrial protein synthesis and oxidative phosphorylation. Mutations in AARS2 cause mitochondrial respiratory chain dysfunction, leading to tissue-specific disorders primarily affecting the brain and heart.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Combined oxidative phosphorylation deficiency 8 (COXPD8) | Loss-of-function mutations impair mitochondrial alanyl-tRNA charging, reducing translation of mtDNA-encoded proteins and ATP production. | ClinVar, OMIM |
| Leukoencephalopathy with progressive cerebellar ataxia | AARS2 mutations disrupt mitochondrial protein synthesis in oligodendrocytes, causing white matter degeneration. | OMIM, PubMed |
| Cardiomyopathy, infantile hypertrophic | Defective mitochondrial translation in cardiac muscle leads to energy deficiency and hypertrophic remodeling. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Skeletal Muscle | 7.1 | Medium |
| Liver | 4.2 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | High expression |
| HEK293 | 8.9 | Medium expression |
| K562 | 6.5 | Medium expression |
| HepG2 | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1774C>T (p.Arg592Trp) | Missense | Rare | Loss of enzyme activity; associated with leukoencephalopathy |
| c.2269C>T (p.Arg757Cys) | Missense | Rare | Impaired tRNA binding; linked to cardiomyopathy |
| c.908G>A (p.Arg303Gln) | Missense | Rare | Reduced catalytic efficiency; COXPD8 phenotype |
Mutation functional classification
Loss of Function (LOF)
Most AARS2 mutations are recessive loss-of-function, reducing or abolishing mitochondrial alanyl-tRNA synthetase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004813 - alanine-tRNA ligase activity | • GO:0005739 - mitochondrion |
| • GO:0006419 - alanyl-tRNA aminoacylation | • GO:0032543 - mitochondrial translation |
Pathways
• Mitochondrial tRNA aminoacylation (Reactome: R-HSA-379716)
• Mitochondrial translation (Reactome: R-HSA-5368287)
Protein Summary
AARS2 is a 985-amino acid mitochondrial enzyme that catalyzes the ATP-dependent ligation of alanine to its cognate mitochondrial tRNA. The protein contains a catalytic domain and an editing domain that ensures aminoacylation fidelity. Defects in AARS2 lead to impaired mitochondrial protein synthesis, causing energy metabolism disorders such as leukoencephalopathy and hypertrophic cardiomyopathy.
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