TARS2 Gene

HGNC Family	Aminoacyl tRNA synthetases
Name	threonyl-tRNA synthetase 2, mitochondrial (putative)
Description	This gene encodes a member of the class-II aminoacyl-tRNA synthetase family. The encoded protein is a mitochondrial aminoacyl-tRNA synthetase. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 4. [provided by RefSeq, Dec 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have established that mutations in TARS2, the gene encoding mitochondrial threonyl-tRNA synthetase, underlie distinct early‐onset mitochondrial encephalopathies. Compound heterozygous variants in TARS2 have been identified in patients exhibiting axial hypotonia, severe psychomotor delay, and neurodevelopmental impairment, in association with deficiencies in one or multiple mitochondrial respiratory chain complexes. In affected tissues, these mutations cause reduced TARS2 protein levels and diminished threonyl-tRNA availability, thereby impairing mitochondrial protein synthesis and respiration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical analyses have shown that wild-type TARS2 plays a canonical role in mitochondrial translation by catalyzing the aminoacylation of mitochondrial tRNAThr with its cognate amino acid, threonine, and by engaging in post-transfer editing to prevent misactivation of non-cognate amino acids such as serine. Notably, the P282L mutation in TARS2 leads to decreases in threonine activation, aminoacylation, and proofreading activities, thus reducing the enzyme’s catalytic efficiency. Moreover, the discovery of alternatively spliced variants encoding truncated proteins that lack the ability to dimerize underscores the diverse and detrimental molecular consequences that may arise from TARS2 genetic alterations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in mitochondrial protein synthesis, TARS2 has been implicated in a novel regulatory mechanism that links threonine availability to cellular growth signaling. Specifically, TARS2 interacts with inactive Rag GTPases—particularly GTP-bound RagC—thereby promoting increased GTP loading of RagA and activating mechanistic target of rapamycin complex 1 (mTORC1) in response to threonine repletion. This threonine-dependent mTORC1 activation is unique to the mitochondrial form of threonyl-tRNA synthetase, as the cytoplasmic counterpart does not participate in this process. Additionally, comprehensive genetic association analyses indicate that common variants in mitochondrial protein synthesis genes, including TARS2, are not significantly linked to type II diabetes mellitus, emphasizing its specialized role in mitochondrial function and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daria Diodato, Laura Melchionda, Tobias B Haack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22590"}], "href": "https://doi.org/10.1002/humu.22590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24827421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24827421"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yong Wang, Xiao-Long Zhou, Zhi-Rong Ruan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.700849"}], "href": "https://doi.org/10.1074/jbc.M115.700849"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26811336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26811336"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaojing Li, Bingwei Peng, Chi Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel compound heterozygous TARS2 variants in a Chinese family with mitochondrial encephalomyopathy: a case report."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-020-01149-0"}], "href": "https://doi.org/10.1186/s12881-020-01149-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33153448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33153448"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andrea Accogli, Sheng-Jia Lin, Mariasavina Severino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gim.2023.100938"}], "href": "https://doi.org/10.1016/j.gim.2023.100938"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37454282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37454282"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sung-Hoon Kim, Jung-Hyun Choi, Peng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.11.036"}], "href": "https://doi.org/10.1016/j.molcel.2020.11.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33340489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33340489"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Erwin Reiling, Jana V van Vliet-Ostaptchouk, Esther van 't Riet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2009.4"}], "href": "https://doi.org/10.1038/ejhg.2009.4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19209188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19209188"}]}]}]}
Synonyms	COXPD21, TARSL1
Proteins	SYTM_HUMAN
NCBI Gene ID	80222
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

TARS2 has 6,846 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 121 datasets.

Click the + buttons to view associations for TARS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

TARS2 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 TARS2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of TARS2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of TARS2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of TARS2 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 TARS2 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 TARS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of TARS2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of TARS2 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 TARS2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of TARS2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of TARS2 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 TARS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with TARS2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with TARS2 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 TARS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of TARS2 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 TARS2 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 TARS2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with TARS2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of TARS2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of TARS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing TARS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing TARS2 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 TARS2 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 TARS2 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 TARS2 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 TARS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with TARS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with TARS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with TARS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with TARS2 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 TARS2 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 TARS2 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 TARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with TARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for TARS2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at TARS2 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 TARS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of TARS2 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 TARS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.