Seroatlas · Human Serome Atlas

VARS2

Valine--tRNA ligase, mitochondrial

Also known as: DKFZP434L1435, G7a, KIAA1885, SYVM_HUMAN, VARS2L, VARSL

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q5ST30
Gene: VARS2
Ensembl: ENSG00000137411
Chromosome: 6
Canonical length: 1063 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
Subcellular location: Mitochondria

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1063 residues, UniProt reviewed canonical sequence.

>Q5ST30|VARS2
     1  MPHLPLASFR PPFWGLRHSR GLPRFHSVST QSEPHGSPIS RRNREAKQKR LREKQATLEA
    61  EIAGESKSPA ESIKAWRPKE LVLYEIPTKP GEKKDVSGPL PPAYSPRYVE AAWYPWWVRE
   121  GFFKPEYQAR LPQATGETFS MCIPPPNVTG SLHIGHALTV AIQDALVRWH RMRGDQVLWV
   181  PGSDHAGIAT QAVVEKQLWK ERGVRRHELS REAFLREVWQ WKEAKGGEIC EQLRALGASL
   241  DWDRECFTMD VGSSVAVTEA FVRLYKAGLL YRNHQLVNWS CALRSAISDI EVENRPLPGH
   301  TQLRLPGCPT PVSFGLLFSV AFPVDGEPDA EVVVGTTRPE TLPGDVAVAV HPDDSRYTHL
   361  HGRQLRHPLM GQPLPLITDY AVQPHVGTGA VKVTPAHSPA DAEMGARHGL SPLNVIAEDG
   421  TMTSLCGDWL QGLHRFVARE KIMSVLSEWG LFRGLQNHPM VLPICSRSGD VIEYLLKNQW
   481  FVRCQEMGAR AAKAVESGAL ELSPSFHQKN WQHWFSHIGD WCVSRQLWWG HQIPAYLVVE
   541  DHAQGEEDCW VVGRSEAEAR EVAAELTGRP GAELTLERDP DVLDTWFSSA LFPFSALGWP
   601  QETPDLARFY PLSLLETGSD LLLFWVGRMV MLGTQLTGQL PFSKVLLHPM VRDRQGRKMS
   661  KSLGNVLDPR DIISGVEMQV LQEKLRSGNL DPAELAIVAA AQKKDFPHGI PECGTDALRF
   721  TLCSHGVQAG DLHLSVSEVQ SCRHFCNKIW NALRFILNAL GEKFVPQPAE ELSPSSPMDA
   781  WILSRLALAA QECERGFLTR ELSLVTHALH HFWLHNLCDV YLEAVKPVLW HSPRPLGPPQ
   841  VLFSCADLGL RLLAPLMPFL AEELWQRLPP RPGCPPAPSI SVAPYPSACS LEHWRQPELE
   901  RRFSRVQEVV QVLRALRATY QLTKARPRVL LQSSEPGDQG LFEAFLEPLG TLGYCGAVGL
   961  LPPGAAAPSG WAQAPLSDTA QVYMELQGLV DPQIQLPLLA ARRYKLQKQL DSLTARTPSE
  1021  GEAGTQRQQK LSSLQLELSK LDKAASHLRQ LMDEPPAPGS PEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VARS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.27
Highest tissue expression: 33 nTPM

Expression across tissuesHPA

Tissue

cerebellum: 33 nTPM
esophagus: 20 nTPM
skeletal muscle: 19 nTPM
liver: 17 nTPM
pituitary gland: 16 nTPM
cerebral cortex: 15 nTPM

Single-cell type

proximal tubule cells: 23 nCPM
astrocytes: 20 nCPM
oligodendrocyte progenitor cells: 17 nCPM
brain inhibitory neurons: 14 nCPM
ependymal cells: 12 nCPM
loop of henle epithelial cells: 11 nCPM

Immune cell

MAIT T-cell: 0.4 nTPM
gdT-cell: 0.3 nTPM
memory B-cell: 0.3 nTPM
memory CD8 T-cell: 0.3 nTPM
plasmacytoid DC: 0.3 nTPM
myeloid DC: 0.2 nTPM

Brain region

midbrain: 3.8 nTPM
cerebellum: 3.7 nTPM
cerebral cortex: 3.6 nTPM
hippocampal formation: 3.4 nTPM
pons: 3.4 nTPM
thalamus: 3.4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VARS2.

Disease | AllUniProt

Conditions VARS2 is implicated in, by any mechanism.

Combined oxidative phosphorylation deficiency 20 (COXPD20) MIM:615917

Disease | GeneticClinVar

48 pathogenic / likely-pathogenic of 648 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Combined oxidative phosphorylation defect type 20
Inborn genetic diseases
Adrenocortical carcinoma, hereditary
VARS2-related disorder
Mitochondrial disease

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.69
gnomAD pLI: 0
gnomAD missense Z: 2.39
DepMap mean gene effect: -0.51
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

valyl-tRNA aminoacylation

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads VARS2 as an antibody target. Whether an autoantibody or antibody against VARS2 could matter depends on whether native VARS2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

VARS2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label VARS2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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