AARS2 Gene

HGNC Family	Aminoacyl tRNA synthetases
Name	alanyl-tRNA synthetase 2, mitochondrial
Description	The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. Aminoacyl-tRNA synthetases play critical roles in mRNA translation by charging tRNAs with their cognate amino acids. The encoded protein is a mitochondrial enzyme that specifically aminoacylates alanyl-tRNA. Mutations in this gene are a cause of combined oxidative phosphorylation deficiency 8. [provided by RefSeq, Dec 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AARS2 encodes the mitochondrial alanyl‐tRNA synthetase, a key enzyme that catalyzes the attachment of alanine to its cognate tRNA<sup>Ala</sup> to ensure accurate mitochondrial protein synthesis. Its function is not limited to aminoacylation alone; AARS2 also exhibits proofreading (editing) activity that prevents mischarging and maintains translational fidelity. Dysfunction of AARS2—whether by impaired tRNA recognition, catalytic disruption, or decreased protein stability—leads to deficient mitochondrial translation and subsequent compromise of oxidative phosphorylation. Such impairments have been linked to a spectrum of tissue‐specific pathologies, including fatal infantile cardiomyopathy, adult‐onset leukoencephalopathy (often accompanied by ovarian failure), optic atrophy, and other neurodegenerative features. In several studies, mutations in AARS2 have been demonstrated to disturb the proper aminoacylation of mitochondrial tRNA<sup>Ala</sup>, triggering combined respiratory chain deficiencies in affected tissues, while distinct mutations may preferentially affect enzyme stability or its editing function. These observations highlight the critical nature of AARS2 in mitochondrial homeostasis and explain the heterogeneous clinical presentations resulting from its loss of function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": " \n Overall, these findings underscore the indispensable role of AARS2 in maintaining mitochondrial translation efficiency and cellular energy metabolism, with its disruption leading to severe, multi‐system mitochondrial disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexandra Götz, Henna Tyynismaa, Liliya Euro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.04.006"}], "href": "https://doi.org/10.1016/j.ajhg.2011.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21549344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21549344"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Cristina Dallabona, Daria Diodato, Sietske H Kevelam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel (ovario) leukodystrophy related to AARS2 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0000000000000497"}], "href": "https://doi.org/10.1212/WNL.0000000000000497"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24808023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24808023"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Neurol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaneurol.2016.2229"}], "href": "https://doi.org/10.1001/jamaneurol.2016.2229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27749956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27749956"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qi-Yu Zeng, Gui-Xin Peng, Guang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The G3-U70-independent tRNA recognition by human mitochondrial alanyl-tRNA synthetase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz078"}], "href": "https://doi.org/10.1093/nar/gkz078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30952159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30952159"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ewen W Sommerville, Xiao-Long Zhou, Monika Oláhová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile-onset cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddy294"}], "href": "https://doi.org/10.1093/hmg/ddy294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30285085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30285085"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yiran Zhou, Beili Chen, Lin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel alanyl-tRNA synthetase 2 (AARS2) homozygous mutation in a consanguineous Chinese family with premature ovarian insufficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2019.05.005"}], "href": "https://doi.org/10.1016/j.fertnstert.2019.05.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31280959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31280959"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Molly E Kuo, Anthony Antonellis, Vikram G Shakkottai "}, {"type": "b", "children": [{"type": "t", "text": "Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cerebellum (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12311-019-01080-y"}], "href": "https://doi.org/10.1007/s12311-019-01080-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31705293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31705293"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Siddharth Srivastava, Ankur Butala, Sonal Mahida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expansion of the clinical spectrum associated with AARS2-related disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.61188"}], "href": "https://doi.org/10.1002/ajmg.a.61188"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31099476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31099476"}]}]}]}
Synonyms	MT-ALARS, COXPD8, LKENP, AARSL, MTALARS
Proteins	SYAM_HUMAN
NCBI Gene ID	57505
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AARS2 has 5,004 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for AARS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AARS2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AARS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of AARS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of AARS2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AARS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AARS2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AARS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AARS2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of AARS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AARS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AARS2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of AARS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AARS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of AARS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with AARS2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AARS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AARS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AARS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing AARS2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AARS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with AARS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of AARS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AARS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AARS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AARS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with AARS2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving AARS2 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving AARS2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with AARS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with AARS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with AARS2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with AARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for AARS2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at AARS2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of AARS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AARS2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing AARS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with AARS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with AARS2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing AARS2 from the GeneSigDB Published Gene Signatures dataset.