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    VARS1 valyl-tRNA synthetase 1 [ Homo sapiens (human) ]

    Gene ID: 7407, updated on 5-May-2024

    Summary

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    Official Symbol
    VARS1provided by HGNC
    Official Full Name
    valyl-tRNA synthetase 1provided by HGNC
    Primary source
    HGNC:HGNC:12651
    See related
    Ensembl:ENSG00000204394 MIM:192150; AllianceGenome:HGNC:12651
    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
    G7A; VARS; VARS2; NDMSCA
    Summary
    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. The protein encoded by this gene belongs to class-I aminoacyl-tRNA synthetase family and is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in testis (RPKM 30.0), appendix (RPKM 11.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6p21.33
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (31777518..31795752, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (31630565..31648800, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31745295..31763529, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene MSH5-SAPCD1 readthrough (NMD candidate) Neighboring gene SAPCD1 antisense RNA 1 Neighboring gene suppressor APC domain containing 1 Neighboring gene Sharpr-MPRA regulatory regions 3149 and 4553 Neighboring gene von Willebrand factor A domain containing 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:31759127-31759287 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:31759783-31760982 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:31763127-31763981 Neighboring gene LSM2 homolog, U6 small nuclear RNA and mRNA degradation associated Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:31782423-31783252 Neighboring gene origin of replication in promoter of HSPA1A Neighboring gene heat shock protein family A (Hsp70) member 1 like

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. Friedman J, et al. Nat Commun, 2019 Feb 12. PMID 30755602, Free PMC Article
    2. Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. Stephen J, et al. Hum Genet, 2018 Apr. PMID 29691655, Free PMC Article
    3. Three-dimensional reconstruction of the valyl-tRNA synthetase/elongation factor-1H complex and localization of the delta subunit. Jiang S, et al. FEBS Lett, 2005 Nov 7. PMID 16229838
    4. Two human valyl-tRNA synthetase-encoding cDNA sequences deposited in GenBank display extensive differences. Motorin Y. Gene, 1996 May 8. PMID 8666263
    5. Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase. Hsieh SL, et al. Biochem J, 1991 Sep 15. PMID 1898367, Free PMC Article

    See all (114) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.
      Title: High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.
    2. Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease.
      Title: Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease.
    3. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.
      Title: Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.
    4. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly
      Title: Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    7. The first three-dimensional structure of the the valyl-tRNA synthetase/elongation factor-1H complex as calculated from electron microscopic images of negatively stained samples of the human ValRS/EF-1H complex was obtained.
      Title: Three-dimensional reconstruction of the valyl-tRNA synthetase/elongation factor-1H complex and localization of the delta subunit.
    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
    Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
    MedGen: C4540493 OMIM: 617802 GeneReviews: Not available
    		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)

    Genotypes

    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 aminoacyl-tRNA editing activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables valine-tRNA ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables valine-tRNA ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables valine-tRNA ligase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in aminoacyl-tRNA metabolism involved in translational fidelity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tRNA aminoacylation for protein translation TAS
    Traceable Author Statement
    more info
    		  
    involved_in valyl-tRNA aminoacylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    valine--tRNA ligase
    Names
    protein G7a
    valRS
    valine tRNA ligase 1, cytoplasmic
    valyl-tRNA synthetase 2
    NP_006286.1
    XP_005249419.1
    XP_047275252.1
    XP_047275253.1
    XP_047275254.1
    XP_054184482.1
    XP_054184483.1
    XP_054185836.1
    XP_054185837.1
    XP_054186320.1
    XP_054186321.1
    XP_054186836.1
    XP_054186837.1
    XP_054212286.1
    XP_054212287.1

    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_028229.1 RefSeqGene

      Range
      5184..23418
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006295.3 → NP_006286.1  valine--tRNA ligase

      See identical proteins and their annotated locations for NP_006286.1

      Status: REVIEWED

      Source sequence(s)
      BC012808, CX167000, CX781162, M98326
      Consensus CDS
      CCDS34412.1
      UniProtKB/Swiss-Prot
      B0V1N1, B4DZ61, P26640, Q5JQ90, Q96E77, Q9UQM2
      UniProtKB/TrEMBL
      A0A024RCN6, A0A1U9X9A0, A0A1U9X9A1, A0A1U9X9A3, A0A1U9X9C1, A0A1U9X9C4, A0A1U9X9C8, A0A1U9X9D5
      Related
      ENSP00000364815.3, ENST00000375663.8
      Conserved Domains (2) summary
      cd10294
      Location:92 → 213
      GST_C_ValRS_N; Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase
      cl26128
      Location:282 → 1264
      tRNA-synt_1g; tRNA synthetases class I (M)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      31777518..31795752 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005249362.3 → XP_005249419.1  valine--tRNA ligase isoform X1

      See identical proteins and their annotated locations for XP_005249419.1

      UniProtKB/TrEMBL
      A0A1U9X9A1, A0A1U9X9A3, A0A1U9X9C1, A0A1U9X9C4, A0A1U9X9C8, A0A1U9X9D5
      Conserved Domains (7) summary
      cd07962
      Location:939 → 1076
      Anticodon_Ia_Val; Anticodon-binding domain of valyl tRNA synthetases
      cd00817
      Location:336 → 939
      ValRS_core; catalytic core domain of valyl-tRNA synthetases
      cd10294
      Location:92 → 213
      GST_C_ValRS_N; Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase
      COG0625
      Location:56 → 203
      GstA; Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones]
      PTZ00419
      Location:283 → 1265
      PTZ00419; valyl-tRNA synthetase-like protein; Provisional
      pfam10458
      Location:1197 → 1259
      Val_tRNA-synt_C; Valyl tRNA synthetase tRNA binding arm
      pfam13603
      Location:514 → 610
      tRNA-synt_1_2; Leucyl-tRNA synthetase, Domain 2

    2. XM_047419297.1 → XP_047275253.1  valine--tRNA ligase isoform X3

      UniProtKB/Swiss-Prot
      B0V1N1, B4DZ61, P26640, Q5JQ90, Q96E77, Q9UQM2
      UniProtKB/TrEMBL
      A0A024RCN6, A0A1U9X9A0

    3. XM_047419296.1 → XP_047275252.1  valine--tRNA ligase isoform X1

    4. XM_047419298.1 → XP_047275254.1  valine--tRNA ligase isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_167244.2 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      3110129..3128363 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328507.1 → XP_054184482.1  valine--tRNA ligase isoform X1

    2. XM_054328508.1 → XP_054184483.1  valine--tRNA ligase isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      3254760..3272992 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329861.1 → XP_054185836.1  valine--tRNA ligase isoform X1

    2. XM_054329862.1 → XP_054185837.1  valine--tRNA ligase isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      3025292..3043526 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330345.1 → XP_054186320.1  valine--tRNA ligase isoform X1

    2. XM_054330346.1 → XP_054186321.1  valine--tRNA ligase isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      3119407..3137641 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330861.1 → XP_054186836.1  valine--tRNA ligase isoform X1

    2. XM_054330862.1 → XP_054186837.1  valine--tRNA ligase isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      3047436..3051579 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      3076809..3094270 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      31630565..31648800 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356311.1 → XP_054212286.1  valine--tRNA ligase isoform X1

    2. XM_054356312.1 → XP_054212287.1  valine--tRNA ligase isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P26640.4 GenPept UniProtKB/Swiss-Prot:P26640

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