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    VARS2 valyl-tRNA synthetase 2, mitochondrial [ Homo sapiens (human) ]

    Gene ID: 57176, updated on 27-Nov-2024

    Summary

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    Official Symbol
    VARS2provided by HGNC
    Official Full Name
    valyl-tRNA synthetase 2, mitochondrialprovided by HGNC
    Primary source
    HGNC:HGNC:21642
    See related
    Ensembl:ENSG00000137411 MIM:612802; AllianceGenome:HGNC:21642
    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
    VALRS; VARSL; VARS2L; COXPD20
    Summary
    This gene encodes a mitochondrial aminoacyl-tRNA synthetase, which catalyzes the attachment of valine to tRNA(Val) for mitochondrial translation. Mutations in this gene cause combined oxidative phosphorylation deficiency-20, and are also associated with early-onset mitochondrial encephalopathies. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2014]
    Expression
    Ubiquitous expression in brain (RPKM 7.4), esophagus (RPKM 6.1) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See VARS2 in Genome Data Viewer
    Location:
    6p21.33
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (30914238..30926459)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (30778904..30791138)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (30882015..30894236)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene discoidin domain receptor tyrosine kinase 1 Neighboring gene microRNA 4640 Neighboring gene general transcription factor IIH subunit 4 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:30889690-30890889 Neighboring gene surfactant associated 2 Neighboring gene uncharacterized LOC124901299 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:30905665-30906166

    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. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. Taylor RW, et al. JAMA, 2014 Jul 2. PMID 25058219, Free PMC Article
    2. A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension. Chin HL, et al. J Mol Med (Berl), 2019 Nov. PMID 31529142
    3. Balancing selection is common in the extended MHC region but most alleles with opposite risk profile for autoimmune diseases are neutrally evolving. Cagliani R, et al. BMC Evol Biol, 2011 Jun 17. PMID 21682861, Free PMC Article
    4. VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype. Begliuomini C, et al. BMC Med Genet, 2019 May 7. PMID 31064326, Free PMC Article
    5. A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family. Ma K, et al. BMC Med Genet, 2018 Nov 20. PMID 30458719, Free PMC Article

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Study shows A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension
      Title: A combination of two novel VARS2 variants causes a mitochondrial disorder associated with failure to thrive and pulmonary hypertension.
    2. report two additional cases of two non-related young girls from Sardinia, born from non-consanguineous and healthy parents, carrying the aforesaid homozygous VARS2 variant. At onset both the patients presented with worsening psychomotor delay, muscle hypotonia and brisk tendon reflexes
      Title: VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.
    3. The novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) has been reported in a female infant. These heterozygous mutations were carried individually by the proband's parents and elder sister.
      Title: A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.
    4. this gene should be considered in early-onset mitochondrial encephalomyopathies or encephalocardiomyopathies.
      Title: Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease.
    5. VARS2 mutation underlies a novel autosomal recessive syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism.
      Title: Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism.
    6. VARS2 polymorphism significantly associated with chronic hepatitis B in Korean population.
      Title: Association of VARS2-SFTA2 polymorphisms with the risk of chronic hepatitis B in a Korean population.
    7. VARS2 V552V may be considered as a prognostic factor for survival in patients with early breast cancer.
      Title: VARS2 V552V variant as prognostic marker in patients with early breast cancer.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    9. Data indicate that variations in the levels of VARS2L between tissue types and patients could underlie the difference in clinical presentation between individuals homoplasmic for the 1624C>T MTTV (equivalent to mt-tRNAVal C25U) mutation.
      Title: Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation.
    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
    Combined oxidative phosphorylation defect type 20
    MedGen: C4014660 OMIM: 615917 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Common genetic variation and the control of HIV-1 in humans.
    EBI GWAS Catalog
    Genetic predictors of medically refractory ulcerative colitis.
    EBI GWAS Catalog
    Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Potential readthrough

    Included gene: GTF2H4

    Homology

    Clone Names

    • KIAA1885, MGC138259, MGC142165

    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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in aminoacyl-tRNA metabolism involved in translational fidelity IEA
    Inferred from Electronic Annotation
    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 mitochondrion HTP PubMed 

    General protein information

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    Preferred Names
    valine--tRNA ligase, mitochondrial
    Names
    valine tRNA ligase 2, mitochondrial (putative)
    valyl-tRNA synthetase like
    NP_001161205.1
    NP_001161206.1
    NP_065175.4

    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_034224.1 RefSeqGene

      Range
      5031..17252
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001167733.3 → NP_001161205.1  valine--tRNA ligase, mitochondrial isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains alternate 5' exon structure, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AK293780, AK303415, BC073838
      Consensus CDS
      CCDS54981.1
      UniProtKB/TrEMBL
      A0A140T8Y0
      Related
      ENSP00000485818.1, ENST00000625423.2
      Conserved Domains (3) summary
      cd07962
      Location:594 → 728
      Anticodon_Ia_Val; Anticodon-binding domain of valyl tRNA synthetases
      cd00817
      Location:1 → 594
      ValRS_core; catalytic core domain of valyl-tRNA synthetases
      PTZ00419
      Location:1 → 911
      PTZ00419; valyl-tRNA synthetase-like protein; Provisional

    2. NM_001167734.2 → NP_001161206.1  valine--tRNA ligase, mitochondrial isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK304807, AL669830, BC073838, BC112054
      UniProtKB/TrEMBL
      A0A140TA35, A0A1U9X992, A0A1U9X9A8, A0A1U9X9B3
      Conserved Domains (1) summary
      cl26128
      Location:116 → 1081
      tRNA-synt_1g; tRNA synthetases class I (M)

    3. NM_020442.6 → NP_065175.4  valine--tRNA ligase, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_065175.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains alternate 5' exon structure, and it thus differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AK294451, AK303415, BC073838
      Consensus CDS
      CCDS34387.1
      UniProtKB/Swiss-Prot
      A2ABL7, B4DET4, B4E3P5, F5GXJ0, F5H323, Q2M2A0, Q59FI1, Q5SQ96, Q5SS98, Q5ST30, Q6DKJ5, Q6ZV24, Q96GN2, Q96H77, Q96Q02, Q9H6R2, Q9UFH7
      UniProtKB/TrEMBL
      A0A140T8Y0
      Related
      ENSP00000502585.1, ENST00000676266.1
      Conserved Domains (3) summary
      cd07962
      Location:734 → 868
      Anticodon_Ia_Val; Anticodon-binding domain of valyl tRNA synthetases
      cd00817
      Location:137 → 734
      ValRS_core; catalytic core domain of valyl-tRNA synthetases
      PTZ00419
      Location:86 → 1051
      PTZ00419; valyl-tRNA synthetase-like protein; Provisional

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      30914238..30926459
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      2393984..2406057
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      2170542..2182776
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

      Range
      2224474..2236697
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      2258385..2270615
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      2169404..2181636
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      30778904..30791138
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5ST30.2 GenPept UniProtKB/Swiss-Prot:Q5ST30

    Gene LinkOut

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

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