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

Gene ID: 57176, updated on 2-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 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)

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

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

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