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    HARS2 histidyl-tRNA synthetase 2, mitochondrial [ Homo sapiens (human) ]

    Gene ID: 23438, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HARS2provided by HGNC
    Official Full Name
    histidyl-tRNA synthetase 2, mitochondrialprovided by HGNC
    Primary source
    HGNC:HGNC:4817
    See related
    Ensembl:ENSG00000112855 MIM:600783; AllianceGenome:HGNC:4817
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HO3; HARSL; HARSR; HisRS; PRLTS2
    Summary
    Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is an enzyme belonging to the class II family of aminoacyl-tRNA synthetases. Functioning in the synthesis of histidyl-transfer RNA, the enzyme plays an accessory role in the regulation of protein biosynthesis. The gene is located in a head-to-head orientation with HARS on chromosome five, where the homologous genes likely share a bidirectional promoter. Mutations in this gene are associated with the pathogenesis of Perrault syndrome, which involves ovarian dysgenesis and sensorineural hearing loss. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]
    Expression
    Ubiquitous expression in colon (RPKM 9.6), endometrium (RPKM 9.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HARS2 in Genome Data Viewer
    Location:
    5q31.3
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (140691455..140699305)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (141216842..141224701)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (140071040..140078890)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:140052035-140052830 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:140052831-140053626 Neighboring gene WD repeat domain 55 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23284 Neighboring gene DND microRNA-mediated repression inhibitor 1 Neighboring gene histidyl-tRNA synthetase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23285 Neighboring gene HARS1 and HARS2 bidirectional promoter region Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23288 Neighboring gene NANOG hESC enhancer GRCh37_chr5:140082322-140082864 Neighboring gene zinc finger matrin-type 2 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:140090124-140091323 Neighboring gene uncharacterized LOC105378198 Neighboring gene vault RNA 1-1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome. Karstensen HG, et al. Eur J Med Genet, 2020 Mar. PMID 31449985
    2. Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation. Gong S, et al. J Biol Chem, 2020 Jan 24. PMID 31819004, Free PMC Article
    3. A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families. Demain LAM, et al. J Hum Genet, 2020 Mar. PMID 31827252, Free PMC Article
    4. Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss. Yu J, et al. Hereditas, 2020 Nov 24. PMID 33228777, Free PMC Article
    5. [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes]. Lei YB, et al. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2023 Dec 7. PMID 38186093

    See all (64) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].
      Title: [Analysis of perrault syndrome caused by pathogenic variants in LARS2 and HARS2 genes].
    2. Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss.
      Title: Two novel likely pathogenic variants of HARS2 identified in a Chinese family with sensorineural hearing loss.
    3. Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome.
      Title: Novel HARS2 missense variants identified in individuals with sensorineural hearing impairment and Perrault syndrome.
    4. A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.
      Title: A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.
    5. Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation.
      Title: Overexpression of mitochondrial histidyl-tRNA synthetase restores mitochondrial dysfunction caused by a deafness-associated tRNA(His) mutation.
    6. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome.
      Title: Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    8. This protein has been found differentially expressed in the anterior cingulate cortex in men patients with schizophrenia.
      Title: Sex-specific proteome differences in the anterior cingulate cortex of schizophrenia.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Perrault syndrome 2
    MedGen: C3554105 OMIM: 614926 GeneReviews: Perrault Syndrome
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    matrix gag HIV-1 MA is identified to have a physical interaction with histidyl-tRNA synthetase 2, mitochondrial (HARS2; HO3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    gag HO3 binds to the HIV-1 Matrix protein (amino acids 26 and 27) resulting in the incorporation of HO3 into virus particles and the enhancement of virus infectivity PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables RNA binding HDA PubMed 
    enables RNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histidine-tRNA ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histidine-tRNA ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histidine-tRNA ligase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables histidine-tRNA ligase activity TAS
    Traceable Author Statement
    more info
    		  
    enables identical protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in histidyl-tRNA aminoacylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in histidyl-tRNA aminoacylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tRNA aminoacylation for protein translation TAS
    Traceable Author Statement
    more info
    		  
    involved_in translation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    histidine--tRNA ligase, mitochondrial
    Names
    HARS-related
    histidine tRNA ligase 2, mitochondrial (putative)
    histidine translase
    histidine-tRNA ligase homolog
    histidyl-tRNA synthetase 2, mitochondrial (putative)
    histidyl-tRNA synthetase 2, mitochondrial, hisRS
    probable histidine--tRNA ligase, mitochondrial
    probable histidyl-tRNA synthetase, mitochondrial
    NP_001265660.1
    NP_001265661.1
    NP_001350464.1
    NP_001350465.1
    NP_036340.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_021415.1 RefSeqGene

      Range
      5023..12873
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1376

    mRNA and Protein(s)

    1. NM_001278731.2 → NP_001265660.1  histidine--tRNA ligase, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_001265660.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which lacks an internal segment and is shorter than isoform 1.
      Source sequence(s)
      AK293390, BC014982, DA150729
      Consensus CDS
      CCDS64267.1
      UniProtKB/TrEMBL
      B2R7G6
      Related
      ENSP00000423616.1, ENST00000508522.5
      Conserved Domains (1) summary
      PLN02972
      Location:36 → 479
      PLN02972; Histidyl-tRNA synthetase

    2. NM_001278732.2 → NP_001265661.1  histidine--tRNA ligase, mitochondrial isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site and lacks two alternate in-frame exons in the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1. This isoform (3) lacks the transit peptide present in isoforms 1 and 2, hence it is not likely to localize to the mitochondrion.
      Source sequence(s)
      AK293269, BC014982, BQ228600, DA150729
      UniProtKB/TrEMBL
      B4DDN8
      Conserved Domains (2) summary
      cd00773
      Location:32 → 251
      HisRS-like_core; Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain. HisRS is a homodimer. It is responsible for the attachment of histidine to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent ...
      cd00859
      Location:265 → 356
      HisRS_anticodon; HisRS Histidyl-anticodon binding domain. HisRS belongs to class II aminoacyl-tRNA synthetases (aaRS). This alignment contains the anticodon binding domain, which is responsible for specificity in tRNA-binding, so that the activated amino acid is ...

    3. NM_001363535.2 → NP_001350464.1  histidine--tRNA ligase, mitochondrial isoform 4 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (4).
      Source sequence(s)
      AC116353
      Consensus CDS
      CCDS87329.1
      UniProtKB/TrEMBL
      A0A2R8Y5P7, B2R7G6
      Related
      ENSP00000494965.1, ENST00000646468.1
      Conserved Domains (1) summary
      cl28413
      Location:12 → 510
      HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

    4. NM_001363536.2 → NP_001350465.1  histidine--tRNA ligase, mitochondrial isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (5) is shorter at the N-terminus compared to isoform 4.
      Source sequence(s)
      AC116353
      Consensus CDS
      CCDS87330.1
      UniProtKB/TrEMBL
      A0A2R8Y6I1, B2R7G6
      Related
      ENSP00000496011.1, ENST00000642970.1
      Conserved Domains (1) summary
      cl28413
      Location:1 → 434
      HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

    5. NM_012208.4 → NP_036340.1  histidine--tRNA ligase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_036340.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      BC014982, DA150729
      Consensus CDS
      CCDS4238.1
      UniProtKB/Swiss-Prot
      B4DDY8, P49590
      UniProtKB/TrEMBL
      B2R7G6
      Related
      ENSP00000230771.3, ENST00000230771.9
      Conserved Domains (1) summary
      cl28413
      Location:12 → 504
      HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      140691455..140699305
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      141216842..141224701
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49590.1 GenPept UniProtKB/Swiss-Prot:P49590

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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