IARS2 Gene

HGNC Family	Aminoacyl tRNA synthetases
Name	isoleucyl-tRNA synthetase 2, mitochondrial
Description	Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form. This gene encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Dec 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IARS2 encodes the mitochondrial isoleucyl‐tRNA synthetase, a critical enzyme that charges mitochondrial tRNA with isoleucine to ensure proper protein translation within the organelle. Disruption of IARS2 function—whether by mutation or altered expression—leads to impaired mitochondrial translation and respiratory chain dysfunction, which can manifest clinically as multisystem mitochondrial disorders. For instance, homozygous or compound heterozygous mutations in IARS2 have been linked to phenotypes including cataracts, sensorineural hearing loss, growth hormone deficiency, peripheral neuropathy, skeletal dysplasia, and even Leigh syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in mitochondrial protein synthesis, IARS2 has been implicated in oncogenic processes. Several studies using RNA interference in cancer cell models—including colon, gastric, non‐small cell lung, and acute myeloid leukemia cells—have demonstrated that knockdown of IARS2 markedly inhibits cell proliferation, alters cell cycle progression, and promotes apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, the IARS2 gene serves as the host for intronic miR‐215, which appears to function in concert with IARS2 to regulate neuronal migration and proliferation. Dysregulation of this IARS2–miR‐215 axis has been associated with Hirschsprung’s disease, highlighting an additional layer through which IARS2 influences cellular processes outside canonical mitochondrial translation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore the multifaceted role of IARS2 in maintaining mitochondrial translation fidelity and cellular homeostasis. Its disruption not only underlies a spectrum of mitochondrial disorders but also modulates tumorigenic processes, making IARS2 a promising candidate for both diagnostic evaluation and therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeremy Schwartzentruber, Daniela Buhas, Jacek Majewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome."}]}, {"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.22629"}], "href": "https://doi.org/10.1002/humu.22629"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25130867"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25130867"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jin Sook Lee, Taekyeong Yoo, Moses Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic heterogeneity in Leigh syndrome: Highlighting treatable and novel genetic causes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.13713"}], "href": "https://doi.org/10.1111/cge.13713"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32020600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32020600"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Samir Jabbour, Mona Harissi-Dagher "}, {"type": "b", "children": [{"type": "t", "text": "Recessive Mutation in a Nuclear-Encoded Mitochondrial tRNA Synthetase Associated With Infantile Cataract, Congenital Neurotrophic Keratitis, and Orbital Myopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cornea (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/ICO.0000000000000847"}], "href": "https://doi.org/10.1097/ICO.0000000000000847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27078007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27078007"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ling Zhong, Yi Zhang, Jing-Yu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of IARS2 gene in colon cancer and effect of its knockdown on biological behavior of RKO cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26722399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26722399"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zheng Fang, Xingyu Wang, Qiang Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-017-3213-8"}], "href": "https://doi.org/10.1007/s11010-017-3213-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29071539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29071539"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hong Li, Yaning Tian, Xiang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of IARS2 Inhibited Proliferation of Acute Myeloid Leukemia Cells by Regulating p53/p21/PCNA/eIF4E Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504018X15426261956343"}], "href": "https://doi.org/10.3727/096504018X15426261956343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30832756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30832756"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "J Yin, W Liu, R Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2016_008"}], "href": "https://doi.org/10.4149/neo_2016_008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26639235"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26639235"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hao Lei, Hongxing Li, Hua Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of MiR-215 in Hirschsprung's Disease Pathogenesis by Targeting SIGLEC-8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000453214"}], "href": "https://doi.org/10.1159/000453214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28006787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28006787"}]}]}]}
Synonyms	CAGSSS
Proteins	SYIM_HUMAN
NCBI Gene ID	55699
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

IARS2 has 6,898 functional associations with biological entities spanning 8 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) extracted from 124 datasets.

Click the + buttons to view associations for IARS2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

IARS2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by IARS2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with IARS2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of IARS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of IARS2 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 IARS2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with IARS2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing IARS2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of IARS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing IARS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing IARS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing IARS2 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 IARS2 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 IARS2 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 IARS2 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 IARS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with IARS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with IARS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving IARS2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with IARS2 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 IARS2 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 IARS2 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 IARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with IARS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for IARS2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at IARS2 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 IARS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of IARS2 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 IARS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with IARS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.