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

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal brain morphology	Likely pathogenic	rs769369302	RCV000454297	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC INTERSTITIAL CYSTITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 20	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OCULAR HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATOID ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SARCOIDOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VARS1-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Astigmatism	Astigmatism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	28763374		★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	29691655	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Primary Microcephaly	Primary microcephaly	Pubtator	30755602	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	30755602	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	39940786	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Combined oxidative phosphorylation defect type 20	Combined Oxidative Phosphorylation Deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	31932636	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	30755616		★☆☆☆☆ Found in Text Mining only
Epilepsia Partialis Continua	Epilepsia Partialis Continua	BEFREE	29314548		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	30755616		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	30755602		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	29314548		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	30755602	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	36303162	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	29691655, 30755616		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	29691655	Associate	★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29314548	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial encephalopathy	Mitochondrial encephalopathy	Pubtator	31064326	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	37587064	Associate	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	30755602	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	29691655		★☆☆☆☆ Found in Text Mining only
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND CORTICAL ATROPHY	Neurodevelopmental Disorder With Microcephaly, Seizures, And Cortical Atrophy	UNIPROT_DG	26539891		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND CORTICAL ATROPHY	Neurodevelopmental Disorder With Microcephaly, Seizures, And Cortical Atrophy	GENOMICS_ENGLAND_DG	29691655, 30275004		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND CORTICAL ATROPHY	Neurodevelopmental Disorder With Microcephaly, Seizures, And Cortical Atrophy	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30370994		★☆☆☆☆ Found in Text Mining only
Neurofibromatosis 1	Neurofibromatosis	BEFREE	30381327		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	34793589	Associate	★☆☆☆☆ Found in Text Mining only
Pena Shokeir syndrome type 1	Pena-shokeir syndrome	Pubtator	34636181	Associate	★☆☆☆☆ Found in Text Mining only
Psychomotor Disorders	Psychiatric disorders	Pubtator	29314548	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	GWASDB_DG	21156761		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoidosis	Sarcoidosis	GWASCAT_DG	26651848		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma Kaposi	Sarcoma	Pubtator	25008864	Associate	★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	29691655	Associate	★☆☆☆☆ Found in Text Mining only
Tremor	Tremor	Pubtator	34636181	Associate	★☆☆☆☆ Found in Text Mining only