VARS1 (valyl-tRNA synthetase 1)

Gene

• Entrez ID: 7407
• Gene name: Valyl-tRNA synthetase 1
• Gene symbol: VARS1
• Synonyms (NCBI Gene): G7A, NDMSCA, VARS, VARS2
• Chromosome: 6
• Chromosome location: 6p21.33
• Summary: 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 prot

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs149378938	G>A,C	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs150882285	C>A,T	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs376864621	C>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs747824231	C>G,T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs749228986	G>A	Uncertain-significance, pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant
rs757026184	->CTGGGCCACAGCCG	Pathogenic	Genic upstream transcript variant, coding sequence variant, non coding transcript variant, frameshift variant
rs762729609	C>G,T	Pathogenic	5 prime UTR variant, missense variant, coding sequence variant, non coding transcript variant
rs763777257	G>A	Pathogenic	5 prime UTR variant, stop gained, coding sequence variant, non coding transcript variant
rs769369302	C>T	Pathogenic, likely-pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant, downstream transcript variant
rs1060499734	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1336685414	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs1401228799	G>T	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs1562293093	C>T	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant, downstream transcript variant
rs1562301511	T>C	Pathogenic	Splice acceptor variant, intron variant
rs1562303235	G>C	Pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant
rs1562303844	T>G	Pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004832	Function	Valine-tRNA ligase activity	IBA
GO:0004832	Function	Valine-tRNA ligase activity	IDA	8428657
GO:0004832	Function	Valine-tRNA ligase activity	IEA
GO:0004832	Function	Valine-tRNA ligase activity	TAS
GO:0005515	Function	Protein binding	IPI	24965446, 25416956, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006438	Process	Valyl-tRNA aminoacylation	IBA
GO:0006438	Process	Valyl-tRNA aminoacylation	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 192150
• HGNC: 12651
• e!Ensembl: ENSG00000204394

Protein

• UniProt ID: P26640
• Protein name: Valine--tRNA ligase (EC 6.1.1.9) (Protein G7a) (Valyl-tRNA synthetase) (ValRS)
• Protein function: Catalyzes the attachment of valine to tRNA(Val).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00043	GST_C	97 → 198	Glutathione S-transferase, C-terminal domain	Domain
  PF00133	tRNA-synt_1	308 → 939	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	984 → 1139	Anticodon-binding domain of tRNA ligase	Domain

• Sequence:

  MSTLYVSPHPDAFPSLRALIAARYGEAGEGPGWGGAHPRICLQPPPTSRTPFPPPRLPAL
  EQGPGGLWVWGATAVAQLLWPAGLGGPGGSRAAVLVQQWVSYADTELIPAACGATLPALG
  LRSSAQDPQAVLGALGRALSPLEEWLRLHTYLAGEAPTLADLAAVTALLLPFRYVLDPPA
  RRIWNNVTRWFVTCVRQPEFRAVLGEVVLYSGARPLSHQPGPEAPALPKTAAQLKKEAKK
  REKLEKFQQKQKIQQQQPPPGEKKPKPEKREKRDPGVITYDLPTPPGEKKDVSGPMPDSY
  SPRYVEAAWYPWWEQQGFFKPEYGRPNVSAANPRGVFMMCIPPPNVTGSLHLGHALTNAI
  QDSLTRWHRMRGETTLWNPGCDHAGIATQVVVEKKLWREQGLSRHQLGREAFLQEVWKWK
  EEKGDRIYHQLKKLGSSLDWDRACFTMDPKLSAAVTEAFVRLHEEGIIYRSTRLVNWSCT
  LNSAISDIEVDKKELTGRTLLSVPGYKEKVEFGVLVSFAYKVQGSDSDEEVVVATTRIET
  MLGDVAVAVHPKDTRYQHLKGKNVIHPFLSRSLPIVFDEFVDMDFGTGAVKITPAHDQND
  YEVGQRHGLEAISIMDSRGALINVPPPFLGLPRFEARKAVLVALKERGLFRGIEDNPMVV
  PLCNRSKDVVEPLLRPQWYVRCGEMAQAASAAVTRGDLRILPEAHQRTWHAWMDNIREWC
  ISRQLWWGHRIPAYFVTVSDPAVPPGEDPDGRYWVSGRNEAEAREKAAKEFGVSPDKISL
  QQDEDVLDTWFSSGLFPLSILGWPNQSEDLSVFYPGTLLETGHDILFFWVARMVMLGLKL
  TGRLPFREVYLHAIVRDAHGRKMSKSLGNVIDPLDVIYGISLQGLHNQLLNSNLDPSEVE
  KAKEGQKADFPAGIPECGTDALRFGLCAYMSQGRDINLDVNRILGYRHFCNKLWNATKFA
  LRGLGKGFVPSPTSQPGGHESLVDRWIRSRLTEAVRLSNQGFQAYDFPAVTTAQYSFWLY
  ELCDVYLECLKPVLNGVDQVAAECARQTLYTCLDVGLRLLSPFMPFVTEELFQRLPRRMP
  QAPPSLCVTPYPEPSECSWKDPEAEAALELALSITRAVRSLRADYNLTRIRPDCFLEVAD
  EATGALASAVSGYVQALASAGVVAVLALGAPAPQGCAVALASDRCSIHLQLQGLVDPARE
  LGKLQAKRVEAQRQAQRLRERRAASGYPVKVPLEVQEADEAKLQQTEAELRKVDEAIALF
  QKML

• Sequence length: 1264

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Abnormal brain morphology	Likely pathogenic	rs769369302	RCV000454297
Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy	Pathogenic; Likely pathogenic	rs1812931789, rs765740144, rs2151419208, rs2537589468, rs2537599374, rs2480864905, rs769369302, rs747824231, rs763777257, rs149378938, rs1336685414, rs376864621, rs1562303235, rs757026184, rs1562301511, rs1562293093, rs776596987, rs373279419, rs746631390, rs2151417852, rs764895082	RCV001333520 RCV001542283 RCV001814917 RCV003388306 RCV003493393 RCV004586241 RCV000516160 RCV000678684 RCV000678685 RCV000754486 RCV000681460 RCV000681456 RCV000681455 RCV000681459 RCV000721128 RCV000721129 RCV001095657 RCV001254051 RCV001254052 RCV001528151 RCV001528152

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs115320814	RCV005902445
Clear cell carcinoma of kidney	Benign	rs115320814	RCV005902446
Gastric cancer	Benign	rs115320814	RCV005902447
Ovarian serous cystadenocarcinoma	Uncertain significance; Benign	rs763964925, rs115320814	RCV005920722 RCV005902448
See cases	Uncertain significance	rs1401631657	RCV002253016
VARS1-related disorder	Uncertain significance; Likely benign; Benign	rs141442235, rs761105119, rs1207589918, rs369903710, rs777386611, rs145504112, rs200588763, rs577647216, rs181542871, rs150822918, rs2480951410, rs776894128, rs768271792, rs707926, rs143269038, rs35196751, rs115320814, rs148951521, rs201902100	RCV003928982 RCV003929153 RCV003964673 RCV003912216 RCV003912302 RCV003937344 RCV003929415 RCV003951836 RCV003934410 RCV003957153 RCV003944277 RCV003971710 RCV003968957 RCV003976506 RCV003926197 RCV003972850 RCV003920506 RCV003920510 RCV003920838

Associations from Text Mining
Disease Name	Relationship Type	References
Atrophy	Associate	29691655
Autosomal Recessive Primary Microcephaly	Associate	30755602
Brain Diseases	Associate	30755602
Breast Neoplasms	Associate	39940786
Diabetes Mellitus Type 2	Associate	31932636
Epilepsia Partialis Continua	Associate	29314548
Intellectual Disability	Associate	30755602
Melanoma	Associate	36303162
Microcephaly	Associate	29691655
Mitochondrial Diseases	Associate	29314548
Mitochondrial encephalopathy	Associate	31064326
Multiple Myeloma	Associate	37587064
Neoplasms	Associate	30381327, 36303162
Neurodegenerative Diseases	Associate	30755602
Ovarian Neoplasms	Associate	34793589
Pena Shokeir syndrome type 1	Associate	34636181
Psychomotor Disorders	Associate	29314548
Sarcoma Kaposi	Associate	25008864
Seizures	Associate	29691655
Tremor	Associate	34636181