| Name | histidyl-tRNA synthetase 1 |
| Description | Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histidyl‐tRNA synthetase, encoded by HARS1, is a highly conserved enzyme whose canonical role is to ligate histidine to its cognate tRNA—a fundamental step in mRNA translation and protein synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to this essential enzymatic function, pathogenic missense and loss‐of‐function mutations in HARS1 have been directly linked to neurodegenerative disorders such as Charcot–Marie–Tooth disease type 2W and Usher syndrome subtype III, with biochemical studies demonstrating that these mutations compromise aminoacylation activity and protein stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, HARS1 is known as the Jo-1 autoantigen in inflammatory myositis, where both the full-length protein and naturally occurring splice variants—lacking portions of the catalytic domain and potentially adopting alternative conformations—are implicated in breaking immunological tolerance and triggering T- and B-cell mediated responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": " Together, these findings illustrate that HARS1 not only fulfills a central role in protein translation but, when its function is perturbed or its alternative forms are expressed, it can contribute to a spectrum of clinical phenotypes ranging from neurodegeneration to autoimmune muscle disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Erik G Puffenberger, Robert N Jinks, Carrie Sougnez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic mapping and exome sequencing identify variants associated with five novel diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0028936"}], "href": "https://doi.org/10.1371/journal.pone.0028936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22279524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22279524"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jamie A Abbott, Rebecca Meyer-Schuman, Vincenzo Lupo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.23380"}], "href": "https://doi.org/10.1002/humu.23380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29235198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29235198"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daniele Galatolo, Molly E Kuo, Patrick Mullen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.24024"}], "href": "https://doi.org/10.1002/humu.24024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32333447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32333447"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhiwen Xu, Zhiyi Wei, Jie J Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2012.08.001"}], "href": "https://doi.org/10.1016/j.str.2012.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22958643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22958643"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jie J Zhou, Feng Wang, Zhiwen Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C114.571026"}], "href": "https://doi.org/10.1074/jbc.C114.571026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24898250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24898250"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lisa Harlow, Irina Fernandez, Makoto Soejima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of TLR4-mediated auto-antibody production in a mouse model of histidyl-tRNA synthetase-induced myositis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Innate Immun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1753425912446714"}], "href": "https://doi.org/10.1177/1753425912446714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22582345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22582345"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "N Bizien, A Renault, J-M Boles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Acute interstitial lung disease revealing antisynthetase syndrome]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rev Pneumol Clin (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pneumo.2011.01.003"}], "href": "https://doi.org/10.1016/j.pneumo.2011.01.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22137282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22137282"}]}]}]}
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| NCBI Gene ID | 3035 |
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| Predicted Functions |
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| Expression in Tissues and Cell Lines |
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HARS1 has 2,347 functional associations with biological entities spanning 5 categories (chemical, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 39 datasets.
Click the + buttons to view associations for HARS1 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of HARS1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of HARS1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Proteomics | Cell lines associated with HARS1 protein from the CCLE Cell Line Proteomics dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of HARS1 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 HARS1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of HARS1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CM4AI U2OS Cell Map Protein Localization Assemblies | assemblies containing HARS1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with HARS1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores 2025 | diseases involving HARS1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with HARS1 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 HARS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with HARS1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving HARS1 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving HARS1 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by HARS1 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by HARS1 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of HARS1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of HARS1 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with HARS1 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of HARS1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of HARS1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| KEGG Pathways 2026 | pathways involving HARS1 protein from the KEGG Pathways 2026 dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of HARS1 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of HARS1 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by HARS1 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of HARS1 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| MW Enzyme Metabolite Associations | interacting metabolites for HARS1 protein from the MW Gene Metabolite Associations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving HARS1 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| Reactome Pathways 2024 | pathways involving HARS1 protein from the Reactome Pathways 2024 dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of HARS1 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of HARS1 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of HARS1 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of HARS1 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of HARS1 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sci-Plex Drug Perturbation Signatures | drug perturbations changing expression of HARS1 gene from the Sci-Plex Drug Perturbation Signatures dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of HARS1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of HARS1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with HARS1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving HARS1 protein from the WikiPathways Pathways 2024 dataset. | |
