Seroatlas · Human Serome Atlas

VARS1

Valine--tRNA ligase

Also known as: SYVC_HUMAN, VARS, VARS2

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

Protein identityUniProt · HPA

UniProt accession: P26640
Gene: VARS1
Ensembl: ENSG00000204394
Chromosome: 6
Canonical length: 1264 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Endoplasmic reticulum,Cytosol,Mid piece,Principal piece,End piece

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1264 residues, UniProt reviewed canonical sequence.

>P26640|VARS1
     1  MSTLYVSPHP DAFPSLRALI AARYGEAGEG PGWGGAHPRI CLQPPPTSRT PFPPPRLPAL
    61  EQGPGGLWVW GATAVAQLLW PAGLGGPGGS RAAVLVQQWV SYADTELIPA ACGATLPALG
   121  LRSSAQDPQA VLGALGRALS PLEEWLRLHT YLAGEAPTLA DLAAVTALLL PFRYVLDPPA
   181  RRIWNNVTRW FVTCVRQPEF RAVLGEVVLY SGARPLSHQP GPEAPALPKT AAQLKKEAKK
   241  REKLEKFQQK QKIQQQQPPP GEKKPKPEKR EKRDPGVITY DLPTPPGEKK DVSGPMPDSY
   301  SPRYVEAAWY PWWEQQGFFK PEYGRPNVSA ANPRGVFMMC IPPPNVTGSL HLGHALTNAI
   361  QDSLTRWHRM RGETTLWNPG CDHAGIATQV VVEKKLWREQ GLSRHQLGRE AFLQEVWKWK
   421  EEKGDRIYHQ LKKLGSSLDW DRACFTMDPK LSAAVTEAFV RLHEEGIIYR STRLVNWSCT
   481  LNSAISDIEV DKKELTGRTL LSVPGYKEKV EFGVLVSFAY KVQGSDSDEE VVVATTRIET
   541  MLGDVAVAVH PKDTRYQHLK GKNVIHPFLS RSLPIVFDEF VDMDFGTGAV KITPAHDQND
   601  YEVGQRHGLE AISIMDSRGA LINVPPPFLG LPRFEARKAV LVALKERGLF RGIEDNPMVV
   661  PLCNRSKDVV EPLLRPQWYV RCGEMAQAAS AAVTRGDLRI LPEAHQRTWH AWMDNIREWC
   721  ISRQLWWGHR IPAYFVTVSD PAVPPGEDPD GRYWVSGRNE AEAREKAAKE FGVSPDKISL
   781  QQDEDVLDTW FSSGLFPLSI LGWPNQSEDL SVFYPGTLLE TGHDILFFWV ARMVMLGLKL
   841  TGRLPFREVY LHAIVRDAHG RKMSKSLGNV IDPLDVIYGI SLQGLHNQLL NSNLDPSEVE
   901  KAKEGQKADF PAGIPECGTD ALRFGLCAYM SQGRDINLDV NRILGYRHFC NKLWNATKFA
   961  LRGLGKGFVP SPTSQPGGHE SLVDRWIRSR LTEAVRLSNQ GFQAYDFPAV TTAQYSFWLY
  1021  ELCDVYLECL KPVLNGVDQV AAECARQTLY TCLDVGLRLL SPFMPFVTEE LFQRLPRRMP
  1081  QAPPSLCVTP YPEPSECSWK DPEAEAALEL ALSITRAVRS LRADYNLTRI RPDCFLEVAD
  1141  EATGALASAV SGYVQALASA GVVAVLALGA PAPQGCAVAL ASDRCSIHLQ LQGLVDPARE
  1201  LGKLQAKRVE AQRQAQRLRE RRAASGYPVK VPLEVQEADE AKLQQTEAEL RKVDEAIALF
  1261  QKML

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VARS1 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): 0.26
Highest tissue expression: 63 nTPM

Expression across tissuesHPA

Tissue

testis: 63 nTPM
skeletal muscle: 56 nTPM
pancreas: 37 nTPM
pituitary gland: 34 nTPM
skin: 33 nTPM
esophagus: 32 nTPM

Single-cell type

late spermatids: 211 nCPM
early spermatids: 161 nCPM
erythrocyte progenitors: 41 nCPM
gastric progenitor cells: 39 nCPM
extravillous trophoblasts: 33 nCPM
late primary spermatocytes: 33 nCPM

Immune cell

plasmacytoid DC: 0.6 nTPM
memory B-cell: 0.5 nTPM
myeloid DC: 0.5 nTPM
NK-cell: 0.5 nTPM
total PBMC: 0.5 nTPM
classical monocyte: 0.3 nTPM

Brain region

hypothalamus: 23 nTPM
pons: 22 nTPM
thalamus: 22 nTPM
cerebral cortex: 22 nTPM
midbrain: 22 nTPM
basal ganglia: 22 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VARS1.

Disease | AllUniProt

Conditions VARS1 is implicated in, by any mechanism.

Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy (NDMSCA) MIM:617802

Disease | GeneticClinVar

35 pathogenic / likely-pathogenic of 364 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
Abnormal brain morphology

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): 0.51
gnomAD pLI: 0
DepMap mean gene effect: -1.66
DepMap dependency class: pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of VARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads VARS1 as an antibody target. Whether an autoantibody or antibody against VARS1 could matter depends on whether native VARS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

VARS1 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 VARS1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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