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 ... See more...

Aliases for VARS1 Gene

Aliases for VARS1 Gene

  • Valyl-TRNA Synthetase 1 2 3 5
  • Valine TRNA Ligase 1, Cytoplasmic 2 3
  • Valyl-TRNA Synthetase 2 2 3
  • Valyl-TRNA Synthetase 2 4
  • Valine--TRNA Ligase 3 4
  • Protein G7a 3 4
  • EC 6.1.1.9 4 50
  • VARS2 3 4
  • ValRS 3 4
  • VARS 3 4
  • G7A 3 4
  • EC 6.1.1 50
  • NDMSCA 3
  • VARS1 5

External Ids for VARS1 Gene

Previous HGNC Symbols for VARS1 Gene

  • VARS2
  • VARS

Previous GeneCards Identifiers for VARS1 Gene

  • GC09U990076
  • GC06M031850
  • GC06M032221
  • GC06M032379
  • GC06M032632
  • GC06M033046

Summaries for VARS1 Gene

Entrez Gene Summary for VARS1 Gene

  • 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]

GeneCards Summary for VARS1 Gene

VARS1 (Valyl-TRNA Synthetase 1) is a Protein Coding gene. Diseases associated with VARS1 include Neurodevelopmental Disorder With Microcephaly, Seizures, And Cortical Atrophy and Combined Oxidative Phosphorylation Deficiency 20. Among its related pathways are tRNA Aminoacylation and Amino Acid metabolism. An important paralog of this gene is VARS2.

Gene Wiki entry for VARS1 Gene

No data available for CIViC Summary , UniProtKB/Swiss-Prot Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for VARS1 Gene

Genomics for VARS1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for VARS1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around VARS1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for VARS1

Genomic Locations for VARS1 Gene

Latest Assembly
chr6:31,777,518-31,795,928
(GRCh38/hg38)
Size:
18,411 bases
Orientation:
Minus strand

Previous Assembly
chr6:31,745,295-31,763,529
(GRCh37/hg19 by Entrez Gene)
Size:
18,235 bases
Orientation:
Minus strand

chr6:31,745,295-31,763,730
(GRCh37/hg19 by Ensembl)
Size:
18,436 bases
Orientation:
Minus strand

Alternative Locations (GRCh38/hg38)

  • chr6(ALT_REF_LOCI_1):3,110,129-3,128,363 (-)
  • chr6(ALT_REF_LOCI_2):3,254,760-3,272,992 (-)
  • chr6(ALT_REF_LOCI_3):3,025,292-3,043,526 (-)
  • chr6(ALT_REF_LOCI_5):3,119,407-3,137,641 (-)
  • chr6(ALT_REF_LOCI_6):3,047,436-3,051,579 (-)
  • chr6(ALT_REF_LOCI_7):3,076,809-3,094,270 (-)

Genomic View for VARS1 Gene

Genes around VARS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
VARS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for VARS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Proteins for VARS1 Gene

  • Protein details for VARS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P26640-SYVC_HUMAN
    Recommended name:
    Valine--tRNA ligase
    Protein Accession:
    P26640
    Secondary Accessions:
    • B0V1N1
    • B4DZ61
    • Q5JQ90
    • Q96E77
    • Q9UQM2

    Protein attributes for VARS1 Gene

    Size:
    1264 amino acids
    Molecular mass:
    140476 Da
    Quaternary structure:
    • Forms high-molecular-mass aggregates with elongation factor 1.
    SequenceCaution:
    • Sequence=CAA41990.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for VARS1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VARS1 Gene

Selected DME Specific Peptides for VARS1 Gene

P26640:
  • KITPAHD
  • PPPNVTG
  • GRKMSKS
  • GNVIDPL
  • FWLYELCDVY
  • IYRSTRLVNW
  • WCISRQL
  • YVEAAWYPWW
  • GRDINLD
  • DHAGIATQ
  • LDTWFSS
  • RFEARKAV
  • ISRQLWWGH
  • GFFKPEY
  • AQLKKEAKKREKLEKFQQK
  • GNVIDPLD
  • DILFFWV
  • FCNKLWNA
  • MSKSLGN
  • GTDALRF
  • DVLDTWFS
  • GEKKDVS
  • SAISDIEV
  • AVTEAFVR
  • WWGHRIP
  • EKGDRIYHQLKKLGSSLDWDRACFTMDPKLS
  • EAFVRLHE
  • SDEEVVVATTRIETMLGD

Post-translational modifications for VARS1 Gene

  • Ubiquitination at Lys320, Lys418, Lys952, Lys966, and Lys1262
  • Modification sites at PhosphoSitePlus

Other Protein References for VARS1 Gene

Domains & Families for VARS1 Gene

Gene Families for VARS1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for VARS1 Gene

InterPro:
Blocks:
  • Glutathione S-transferase, N-terminal
  • Aminoacyl-tRNA synthetase, class Ia
  • tRNA synthetase, valyl/leucyl, anticodon-binding
  • Valyl-tRNA synthetase signature

Suggested Antigen Peptide Sequences for VARS1 Gene

GenScript: Design optimal peptide antigens:
  • Valyl-tRNA synthetase (A2ABF3_HUMAN)
  • Valyl-tRNA synthetase (A2ABF4_HUMAN)
  • Valyl-tRNA synthetase (A2BEY0_HUMAN)
  • Valyl-tRNA synthetase (A2BEY1_HUMAN)
  • Valyl-tRNA synthetase (B0V043_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P26640

UniProtKB/Swiss-Prot:

SYVC_HUMAN :
  • Belongs to the class-I aminoacyl-tRNA synthetase family.
Family:
  • Belongs to the class-I aminoacyl-tRNA synthetase family.
genes like me logo Genes that share domains with VARS1: view

Function for VARS1 Gene

Molecular function for VARS1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-valine + tRNA(Val) = AMP + diphosphate + L-valyl-tRNA(Val); Xref=Rhea:RHEA:10704, Rhea:RHEA-COMP:9672, Rhea:RHEA-COMP:9708, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57762, ChEBI:CHEBI:78442, ChEBI:CHEBI:78537, ChEBI:CHEBI:456215; EC=6.1.1.9;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Can be regulated by protein kinase C-dependent phosphorylation.
GENATLAS Biochemistry:
valyl-tRNA synthetase 1

Enzyme Numbers (IUBMB) for VARS1 Gene

Phenotypes From GWAS Catalog for VARS1 Gene

Gene Ontology (GO) - Molecular Function for VARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0002161 aminoacyl-tRNA editing activity IEA --
GO:0004812 aminoacyl-tRNA ligase activity IEA --
GO:0004832 valine-tRNA ligase activity IEA,TAS --
GO:0005515 protein binding IPI 24965446
genes like me logo Genes that share ontologies with VARS1: view
genes like me logo Genes that share phenotypes with VARS1: view

Human Phenotype Ontology for VARS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for research

  • Taconic Biosciences Mouse Models for VARS1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for VARS1

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for VARS1 Gene

Localization for VARS1 Gene

Subcellular locations from

COMPARTMENTS
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 VARS1 gene
Compartment Confidence
cytosol 4
mitochondrion 2
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for VARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with VARS1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for VARS1 Gene

Pathways & Interactions for VARS1 Gene

genes like me logo Genes that share pathways with VARS1: view

Pathways by source for VARS1 Gene

1 BioSystems pathway for VARS1 Gene
1 KEGG pathway for VARS1 Gene

Gene Ontology (GO) - Biological Process for VARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006412 translation IEA --
GO:0006418 tRNA aminoacylation for protein translation IEA,TAS --
GO:0006438 valyl-tRNA aminoacylation IEA,IBA 21873635
GO:0106074 aminoacyl-tRNA metabolism involved in translational fidelity IEA --
genes like me logo Genes that share ontologies with VARS1: view

No data available for SIGNOR curated interactions for VARS1 Gene

Drugs & Compounds for VARS1 Gene

(8) Drugs for VARS1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Valine Approved Nutra Target, Enzyme, substrate 43
Adenosine monophosphate Approved, Investigational Nutra 0
Phosphate Experimental Pharma 0
ATP Investigational Nutra 0

(5) Additional Compounds for VARS1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(HO)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • Pyrophosphoric acid
14000-31-8
genes like me logo Genes that share compounds with VARS1: view

Transcripts for VARS1 Gene

mRNA/cDNA for VARS1 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for VARS1

Alternative Splicing Database (ASD) splice patterns (SP) for VARS1 Gene

No ASD Table

Relevant External Links for VARS1 Gene

GeneLoc Exon Structure for
VARS1

Expression for VARS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for VARS1

SOURCE GeneReport for Unigene cluster for VARS1 Gene:

Hs.520026

Evidence on tissue expression from TISSUES for VARS1 Gene

  • Nervous system(4.7)
  • Liver(4.5)
  • Muscle(4.3)
  • Skin(3.9)
  • Intestine(3.4)
  • Pancreas(2.7)
  • Heart(2.7)
  • Eye(2.5)
  • Blood(2.4)
  • Lung(2.3)
  • Kidney(2.2)
  • Adrenal gland(2.1)
genes like me logo Genes that share expression patterns with VARS1: view

Primer products for research

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for VARS1 Gene

Orthologs for VARS1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for VARS1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia VARS 29 30
  • 99.53 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia VARS 29 30
  • 90.33 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia VARS 29 30
  • 89.77 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Vars 29
  • 87.55 (n)
Mouse
(Mus musculus)
Mammalia Vars 29 16 30
  • 87.23 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 86 (a)
OneToMany
-- 30
  • 63 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia VARS 30
  • 79 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 70 (a)
OneToMany
-- 30
  • 62 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia vars 29
  • 63.38 (n)
Str.11856 29
Zebrafish
(Danio rerio)
Actinopterygii vars 29 30
  • 64.74 (n)
OneToOne
vars2 29
Fruit Fly
(Drosophila melanogaster)
Insecta Aats-val 29 30
  • 61.25 (n)
ManyToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010420 29
  • 59.37 (n)
Worm
(Caenorhabditis elegans)
Secernentea vars-2 29 30
  • 55.07 (n)
ManyToMany
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AAR034W 29
  • 55.03 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D14971g 29
  • 53.2 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VAS1 29 30
  • 52.65 (n)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons TWN2 29
  • 54.03 (n)
Soybean
(Glycine max)
eudicotyledons Gma.16767 29
Rice
(Oryza sativa)
Liliopsida Os03g0694900 29
  • 54.02 (n)
Barley
(Hordeum vulgare)
Liliopsida Hv.3064 29
Wheat
(Triticum aestivum)
Liliopsida Ta.2835 29
Bread mold
(Neurospora crassa)
Ascomycetes NCU01965 29
  • 56.16 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes vrs1 29
  • 53.62 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.3304 29
Species where no ortholog for VARS1 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)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chicken (Gallus gallus)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for VARS1 Gene

ENSEMBL:
Gene Tree for VARS1 (if available)
TreeFam:
Gene Tree for VARS1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for VARS1: view image
Alliance of Genome Resources:
Additional Orthologs for VARS1

Paralogs for VARS1 Gene

Paralogs for VARS1 Gene

genes like me logo Genes that share paralogs with VARS1: view

Variants for VARS1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for VARS1 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
1004093 Uncertain Significance: not provided 31,791,679(-) G/C
NM_006295.3(VARS1):c.1031C>G (p.Pro344Arg)
MISSENSE
1029023 Uncertain Significance: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 31,783,111(-) T/G
NM_006295.3(VARS1):c.1747A>C (p.Met583Leu)
MISSENSE
1029024 Uncertain Significance: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 31,782,734(-) G/A
NM_006295.3(VARS1):c.1874C>T (p.Pro625Leu)
MISSENSE
1029025 Uncertain Significance: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 31,795,198(-) G/A
NM_006295.3(VARS1):c.20C>T (p.Ser7Phe)
MISSENSE
1029026 Uncertain Significance: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 31,782,098(-) G/T
NM_006295.3(VARS1):c.2230C>A (p.Pro744Thr)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for VARS1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for VARS1 Gene

Variant ID Type Subtype PubMed ID
dgv10403n54 CNV loss 21841781
dgv10404n54 CNV loss 21841781
esv3370799 CNV duplication 20981092
nsv1073969 CNV deletion 25765185
nsv1112900 CNV deletion 24896259
nsv1126749 CNV deletion 24896259
nsv601943 CNV loss 21841781
nsv601944 CNV loss 21841781

Variation tolerance for VARS1 Gene

Residual Variation Intolerance Score: 27.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 16.30; 97.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for VARS1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
VARS1
Leiden Open Variation Database (LOVD)
VARS1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VARS1 Gene

Disorders for VARS1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for VARS1 Gene - From: OMI, CVR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search VARS1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SYVC_HUMAN
  • Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA) [MIM:617802]: An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, intellectual disability, severe microcephaly, and cortical atrophy. {ECO:0000269 PubMed:26539891}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Additional Disease Information for VARS1

genes like me logo Genes that share disorders with VARS1: view

No data available for Genatlas for VARS1 Gene

Publications for VARS1 Gene

  1. Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase. (PMID: 1898367) Hsieh SL … Campbell RD (The Biochemical journal 1991) 3 4 22
  2. Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. (PMID: 26539891) Karaca E … Lupski JR (Neuron 2015) 4 72
  3. Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS. (PMID: 15779907) Bonnefond L … Sissler M (Biochemistry 2005) 2 3
  4. Three-dimensional reconstruction of the valyl-tRNA synthetase/elongation factor-1H complex and localization of the delta subunit. (PMID: 16229838) Jiang S … Norcum MT (FEBS letters 2005) 3 22
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for VARS1 Gene

Sources for VARS1 Gene