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

Gene ID: 7407, updated on 3-Apr-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
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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
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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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