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Aliases for HARS Gene

Aliases for HARS Gene

  • Histidyl-TRNA Synthetase 2 3 4 5
  • HisRS 3 4
  • HRS 3 4
  • Histidine TRNA Ligase 1, Cytoplasmic 2
  • Histidine--TRNA Ligase, Cytoplasmic 3
  • Histidine Translase 3
  • Usher Syndrome 3B 2
  • EC 4
  • CMT2W 3
  • USH3B 3

External Ids for HARS Gene

Previous HGNC Symbols for HARS Gene

  • USH3B

Previous GeneCards Identifiers for HARS Gene

  • GC05M139869
  • GC05M140036
  • GC05M140081
  • GC05M140034
  • GC05M135198

Summaries for HARS Gene

Entrez Gene Summary for HARS Gene

  • 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]

GeneCards Summary for HARS Gene

HARS (Histidyl-TRNA Synthetase) is a Protein Coding gene. Diseases associated with HARS include Charcot-Marie-Tooth Disease, Axonal, Type 2W and Usher Syndrome, Type Iiib. Among its related pathways are tRNA Aminoacylation and Allograft rejection. Gene Ontology (GO) annotations related to this gene include nucleotide binding and histidine-tRNA ligase activity. An important paralog of this gene is HARS2.

UniProtKB/Swiss-Prot for HARS Gene

  • Cytoplasmic histidine--tRNA ligase (Probable). Plays a role in axon guidance.

Gene Wiki entry for HARS Gene

Additional gene information for HARS Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HARS Gene

Genomics for HARS Gene

GeneHancer (GH) Regulatory Elements for HARS Gene

Promoters and enhancers for HARS Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J140690 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 650.7 +0.3 313 2.4 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 POLR2B CBX5 HARS2 HARS ZMAT2 TMCO6 LOC102723915 APBB3 HDAC3 ANKHD1 SRA1 PCDHA4
GH05J140710 Promoter/Enhancer 1.6 Ensembl ENCODE 22.2 -19.1 -19122 1.9 CLOCK FEZF1 IRF4 YY1 ZNF213 ZNF143 SP3 SSRP1 ZNF610 GLIS1 GC05P142295 LOC105378198 VTRNA1-1 HARS2 ANKHD1 WDR55 LOC102723915 HDAC3 PCDHB18P PURA
GH05J140717 Promoter/Enhancer 1.6 Ensembl ENCODE 22.2 -27.3 -27274 2.7 MLX IRF4 YY1 ZNF213 E2F8 ZNF416 ZNF143 SP3 PPARGC1A MEF2D GC05P142304 VTRNA1-2 ANKHD1 PURA HARS2 PCDHB18P PCDHB19P HDAC3 WDR55 PCDHGA6
GH05J140725 Promoter/Enhancer 1.6 Ensembl ENCODE 22.1 -34.1 -34120 1.1 PKNOX1 ARNT ARID4B SIN3A ZNF2 IRF4 YY1 POLR2B ZNF766 ZNF213 GC05P142300 VTRNA1-3 ANKHD1 LOC102723915 WDR55 HDAC3 HARS2 TMCO6 FCHSD1 PCDHA4
GH05J140344 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 11.8 +344.8 344760 5.8 PKNOX1 SIN3A ZNF2 ZNF48 GLIS2 ZNF143 FOS ATF7 RUNX3 SP3 HBEGF SRA1 APBB3 HARS2 HARS IK PFDN1 TAF7 CD14 PCDHA7
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HARS on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HARS gene promoter:
  • AREB6
  • PPAR-gamma2
  • PPAR-gamma1
  • Nkx2-5
  • YY1
  • SRF (504 AA)
  • SRF
  • AML1a
  • ARP-1
  • NF-E2 p45

Genomic Locations for HARS Gene

Genomic Locations for HARS Gene
17,959 bases
Minus strand
18,852 bases
Minus strand

Genomic View for HARS Gene

Genes around HARS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HARS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HARS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HARS Gene

Proteins for HARS Gene

  • Protein details for HARS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Histidine--tRNA ligase, cytoplasmic
    Protein Accession:
    Secondary Accessions:
    • B4DHQ1
    • B4DY73
    • D6REN6
    • J3KNE5

    Protein attributes for HARS Gene

    509 amino acids
    Molecular mass:
    57411 Da
    Quaternary structure:
    • Homodimer.
    • Sequence=CAA28956.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HARS Gene

    Alternative splice isoforms for HARS Gene


neXtProt entry for HARS Gene

Post-translational modifications for HARS Gene

  • Ubiquitination at Lys230 and isoforms=475
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for HARS Gene

Domains & Families for HARS Gene

Gene Families for HARS Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the class-II aminoacyl-tRNA synthetase family.
  • Belongs to the class-II aminoacyl-tRNA synthetase family.
genes like me logo Genes that share domains with HARS: view

Function for HARS Gene

Molecular function for HARS Gene

UniProtKB/Swiss-Prot Function:
Cytoplasmic histidine--tRNA ligase (Probable). Plays a role in axon guidance.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + L-histidine + tRNA(His) = AMP + diphosphate + L-histidyl-tRNA(His).
GENATLAS Biochemistry:
histidyl-tRNA synthetase,target autoantibodies in the immune disease polymyositis/dermatomyositis

Enzyme Numbers (IUBMB) for HARS Gene

Gene Ontology (GO) - Molecular Function for HARS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004812 aminoacyl-tRNA ligase activity IEA --
GO:0004821 histidine-tRNA ligase activity TAS --
GO:0005524 ATP binding IEA --
GO:0016874 ligase activity IEA --
GO:0042802 identical protein binding IPI 22958643
genes like me logo Genes that share ontologies with HARS: view
genes like me logo Genes that share phenotypes with HARS: view

Human Phenotype Ontology for HARS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HARS

Clone Products

No data available for Phenotypes From GWAS Catalog , Animal Models , Transcription Factor Targets and HOMER Transcription for HARS Gene

Localization for HARS Gene

Subcellular locations from UniProtKB/Swiss-Prot for HARS Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HARS gene
Compartment Confidence
cytosol 5
mitochondrion 4
nucleus 3

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for HARS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 21464306
GO:0005739 mitochondrion IBA --
GO:0005829 cytosol IDA,TAS --
genes like me logo Genes that share ontologies with HARS: view

Pathways & Interactions for HARS Gene

genes like me logo Genes that share pathways with HARS: view

Pathways by source for HARS Gene

1 BioSystems pathway for HARS Gene
1 KEGG pathway for HARS Gene

Gene Ontology (GO) - Biological Process for HARS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006412 translation NAS 7755634
GO:0006418 tRNA aminoacylation for protein translation IEA,TAS --
GO:0006427 histidyl-tRNA aminoacylation IEA --
GO:0032543 mitochondrial translation IBA --
genes like me logo Genes that share ontologies with HARS: view

No data available for SIGNOR curated interactions for HARS Gene

Drugs & Compounds for HARS Gene

(5) Drugs for HARS Gene - From: DrugBank, ClinicalTrials, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Histidine Approved Nutra Target 50
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0
Hormones Pharma 15237

(1) Additional Compounds for HARS Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
genes like me logo Genes that share compounds with HARS: view

Transcripts for HARS Gene

Unigene Clusters for HARS Gene

Histidyl-tRNA synthetase:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HARS

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HARS Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c · 6d ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11a ·
SP1: - - - - -
SP2: - - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5: - - - - - - - - - - -
SP6: - -
SP7: - - -
SP8: -

ExUns: 11b · 11c ^ 12 ^ 13a · 13b
SP1: -

Relevant External Links for HARS Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HARS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HARS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for HARS Gene

This gene is overexpressed in Lymph node (11.7) and Peripheral blood mononuclear cells (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HARS Gene

Protein tissue co-expression partners for HARS Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HARS Gene:


SOURCE GeneReport for Unigene cluster for HARS Gene:


mRNA Expression by UniProt/SwissProt for HARS Gene:

Tissue specificity: Brain, heart, liver and kidney.

Evidence on tissue expression from TISSUES for HARS Gene

  • Nervous system(5)
  • Lung(4.6)
  • Liver(4.3)
  • Skin(2.9)
  • Kidney(2.4)
  • Intestine(2.2)
  • Muscle(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HARS Gene

Germ Layers:
  • ectoderm
  • mesoderm
  • immune
  • nervous
  • skeletal muscle
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • eyelid
  • head
  • peripheral nervous system
genes like me logo Genes that share expression patterns with HARS: view

No data available for mRNA differential expression in normal tissues for HARS Gene

Orthologs for HARS Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HARS Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HARS 34 33
  • 99.74 (n)
(Bos Taurus)
Mammalia HARS 34 33
  • 90.83 (n)
(Canis familiaris)
Mammalia HARS 34 33
  • 90.7 (n)
(Monodelphis domestica)
Mammalia HARS 34
  • 90 (a)
(Rattus norvegicus)
Mammalia Hars 33
  • 88.85 (n)
(Mus musculus)
Mammalia Hars 16 34 33
  • 88.34 (n)
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 74 (a)
-- 34
  • 58 (a)
(Gallus gallus)
Aves HARS 34 33
  • 77.29 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 73 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100489846 33
  • 67.92 (n)
Str.5457 33
(Danio rerio)
Actinopterygii hars 34 33
  • 73.22 (n)
Dr.4161 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.10028 33
fruit fly
(Drosophila melanogaster)
Insecta CG6335 35
  • 63 (a)
Aats-his 34 33
  • 62.65 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000735 33
  • 61.18 (n)
(Caenorhabditis elegans)
Secernentea hars-1 34 33
  • 57.59 (n)
hrs-1 35
  • 53 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACR187W 33
  • 56.76 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E06381g 33
  • 54.91 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HTS1 36 34 33
  • 54.34 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT3G02760 33
  • 58.18 (n)
(Oryza sativa)
Liliopsida Os05g0150900 33
  • 58.12 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8844 34
  • 63 (a)
Cin.3858 33
bread mold
(Neurospora crassa)
Ascomycetes NCU06914 33
  • 58.47 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes hrs1 33
  • 55.15 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.3858 33
Species where no ortholog for HARS was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HARS Gene

Gene Tree for HARS (if available)
Gene Tree for HARS (if available)
Evolutionary constrained regions (ECRs) for HARS: view image

Paralogs for HARS Gene

Paralogs for HARS Gene

(2) SIMAP similar genes for HARS Gene using alignment to 7 proteins:

  • B4E1C5_HUMAN
  • D6RF05_HUMAN
genes like me logo Genes that share paralogs with HARS: view

Variants for HARS Gene

Sequence variations from dbSNP and Humsavar for HARS Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs113209109 uncertain-significance, Retinitis pigmentosa-deafness syndrome 140,691,368(-) G/A 5_prime_UTR_variant
rs138582560 uncertain-significance, Retinitis pigmentosa-deafness syndrome, Usher syndrome, type 3B 140,679,802(-) G/A coding_sequence_variant, intron_variant, missense_variant
rs139447495 benign, Usher syndrome, type 3B 140,676,721(-) T/C coding_sequence_variant, missense_variant
rs143473232 pathogenic, Charcot-Marie-Tooth disease, axonal, type 2w, Charcot-Marie-Tooth disease 2W (CMT2W) [MIM:616625] 140,679,789(-) G/A/C coding_sequence_variant, intron_variant, missense_variant
rs144322728 uncertain-significance, Charcot-Marie-Tooth disease, axonal, type 2w 140,676,781(-) C/T coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for HARS Gene

Variant ID Type Subtype PubMed ID
nsv830508 CNV loss 17160897
nsv964945 CNV duplication 23825009

Variation tolerance for HARS Gene

Residual Variation Intolerance Score: 43.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.77; 47.13% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HARS Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HARS Gene

Disorders for HARS Gene

MalaCards: The human disease database

(11) MalaCards diseases for HARS Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
charcot-marie-tooth disease, axonal, type 2w
  • cmt2w
usher syndrome, type iiib
  • ush3b
usher syndrome, type iiia
  • ush3a
  • myopathy, familial idiopathic inflammatory; iim
charles bonnet syndrome
  • cbs
- elite association - COSMIC cancer census association via MalaCards
Search HARS in MalaCards View complete list of genes associated with diseases


  • Usher syndrome 3B (USH3B) [MIM:614504]: A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called Charles Bonnet syndrome, involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. {ECO:0000269 PubMed:22279524}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Charcot-Marie-Tooth disease 2W (CMT2W) [MIM:616625]: An autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement. {ECO:0000269 PubMed:22930593, ECO:0000269 PubMed:26072516}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for HARS

genes like me logo Genes that share disorders with HARS: view

No data available for Genatlas for HARS Gene

Publications for HARS Gene

  1. Genetic mapping and exome sequencing identify variants associated with five novel diseases. (PMID: 22279524) Puffenberger EG … Strauss KA (PloS one 2012) 2 3 4 58
  2. A novel gene oriented in a head-to-head configuration with the human histidyl-tRNA synthetase (HRS) gene encodes an mRNA that predicts a polypeptide homologous to HRS. (PMID: 7755634) O'Hanlon TP … Miller FW (Biochemical and biophysical research communications 1995) 3 4 22 58
  3. Transcriptional analyses of the gene region that encodes human histidyl-tRNA synthetase: identification of a novel bidirectional regulatory element. (PMID: 8406012) Tsui HW … Tsui FW (Gene 1993) 3 4 22 58
  4. Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases. (PMID: 1549469) Raben N … Plotz P (Nucleic acids research 1992) 3 4 22 58
  5. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. (PMID: 26072516) Safka Brozkova D … Baets J (Brain : a journal of neurology 2015) 3 4 58

Products for HARS Gene

Sources for HARS Gene

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