VARS2 (valyl-tRNA synthetase 2, mitochondrial)

Gene

• Entrez ID: 57176
• Gene name: Valyl-tRNA synthetase 2, mitochondrial
• Gene symbol: VARS2
• Synonyms (NCBI Gene): COXPD20, VALRS, VARS2L, VARSL
• Chromosome: 6
• Chromosome location: 6p21.33
• Summary: 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 e

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139515727	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs202201763	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs587777583	G>A	Pathogenic	Missense variant, coding sequence variant
rs587777584	C>A	Pathogenic	Missense variant, coding sequence variant
rs587777585	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs775439829	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs777028011	CT>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1554268077	GGG>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs1582173192	->GATG	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1482783	hsa-miR-1827	CLIP-seq
MIRT1482784	hsa-miR-3612	CLIP-seq
MIRT1482785	hsa-miR-650	CLIP-seq
MIRT1482786	hsa-miR-940	CLIP-seq
MIRT2659277	hsa-miR-2355-3p	CLIP-seq
MIRT2659278	hsa-miR-3909	CLIP-seq
MIRT2659279	hsa-miR-4646-3p	CLIP-seq
MIRT2659280	hsa-miR-4762-5p	CLIP-seq
MIRT2659281	hsa-miR-676	CLIP-seq

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	IEA
GO:0004832	Function	Valine-tRNA ligase activity	IMP	24827421
GO:0005515	Function	Protein binding	IPI	25416956, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005829	Component	Cytosol	IBA
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
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: 612802
• HGNC: 21642
• e!Ensembl: ENSG00000137411

Protein

• UniProt ID: Q5ST30
• Protein name: Valine--tRNA ligase, mitochondrial (EC 6.1.1.9) (Valyl-tRNA synthetase) (ValRS) (Valyl-tRNA synthetase-like)
• Protein function: Catalyzes the attachment of valine to tRNA(Val) in a two-step reaction: valine is first activated by ATP to form Val-AMP and then transferred to the acceptor end of tRNA(Val).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	112 → 735	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	779 → 932	Anticodon-binding domain of tRNA ligase	Domain

• Sequence:

  MPHLPLASFRPPFWGLRHSRGLPRFHSVSTQSEPHGSPISRRNREAKQKRLREKQATLEA
  EIAGESKSPAESIKAWRPKELVLYEIPTKPGEKKDVSGPLPPAYSPRYVEAAWYPWWVRE
  GFFKPEYQARLPQATGETFSMCIPPPNVTGSLHIGHALTVAIQDALVRWHRMRGDQVLWV
  PGSDHAGIATQAVVEKQLWKERGVRRHELSREAFLREVWQWKEAKGGEICEQLRALGASL
  DWDRECFTMDVGSSVAVTEAFVRLYKAGLLYRNHQLVNWSCALRSAISDIEVENRPLPGH
  TQLRLPGCPTPVSFGLLFSVAFPVDGEPDAEVVVGTTRPETLPGDVAVAVHPDDSRYTHL
  HGRQLRHPLMGQPLPLITDYAVQPHVGTGAVKVTPAHSPADAEMGARHGLSPLNVIAEDG
  TMTSLCGDWLQGLHRFVAREKIMSVLSEWGLFRGLQNHPMVLPICSRSGDVIEYLLKNQW
  FVRCQEMGARAAKAVESGALELSPSFHQKNWQHWFSHIGDWCVSRQLWWGHQIPAYLVVE
  DHAQGEEDCWVVGRSEAEAREVAAELTGRPGAELTLERDPDVLDTWFSSALFPFSALGWP
  QETPDLARFYPLSLLETGSDLLLFWVGRMVMLGTQLTGQLPFSKVLLHPMVRDRQGRKMS
  KSLGNVLDPRDIISGVEMQVLQEKLRSGNLDPAELAIVAAAQKKDFPHGIPECGTDALRF
  TLCSHGVQAGDLHLSVSEVQSCRHFCNKIWNALRFILNALGEKFVPQPAEELSPSSPMDA
  WILSRLALAAQECERGFLTRELSLVTHALHHFWLHNLCDVYLEAVKPVLWHSPRPLGPPQ
  VLFSCADLGLRLLAPLMPFLAEELWQRLPPRPGCPPAPSISVAPYPSACSLEHWRQPELE
  RRFSRVQEVVQVLRALRATYQLTKARPRVLLQSSEPGDQGLFEAFLEPLGTLGYCGAVGL
  LPPGAAAPSGWAQAPLSDTAQVYMELQGLVDPQIQLPLLAARRYKLQKQLDSLTARTPSE
  GEAGTQRQQKLSSLQLELSKLDKAASHLRQLMDEPPAPGSPEL

• Sequence length: 1063

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

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
Adrenocortical carcinoma, hereditary	Likely pathogenic; Pathogenic	rs200075594	RCV005908962	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Combined oxidative phosphorylation defect type 20	Likely pathogenic; Pathogenic	rs1794789052, rs769768815, rs2150548621, rs2150570235, rs587777583, rs587777584, rs587777585, rs2538661360, rs753139152, rs1554268192, rs1434914864, rs2538630404, rs775439829, rs1554268077, rs777028011, rs143821815, rs772718755, rs753490759, rs200075594, rs1794768738	RCV001330431 RCV001334847 RCV005395087 RCV001808112 RCV000129933 RCV000129935 RCV000129937 RCV002288233 RCV002472145 RCV003324208 RCV003332014 RCV004595400 RCV000578459 RCV000578269 RCV000987662 RCV001201407 RCV001201409 RCV001201410 RCV001201411 RCV001293011	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Germ cell tumor of testis	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND CORTICAL ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign; Likely 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
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VARS2-related disorder	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acidosis Lactic	Lactic acidosis	Pubtator	30458719	Associate	★☆☆☆☆ Found in Text Mining only
Agenesis of Corpus Callosum	Corpus callosum agenesis	Pubtator	31064326	Associate	★☆☆☆☆ Found in Text Mining only
Arrhythmias Cardiac	Cardiac arrhythmias	Pubtator	31623496	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	19116923	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	29137650	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	31623496	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	20503108		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	29314548, 30458719	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	30458719	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Abnormalities	Cardiovascular abnormalities	Pubtator	30458719	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	31064326	Associate	★☆☆☆☆ Found in Text Mining only
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	Combined Oxidative Phosphorylation Deficiency	ORPHANET_DG	24827421, 25058219		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	Combined Oxidative Phosphorylation Deficiency	UNIPROT_DG	24827421, 25058219		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	Combined Oxidative Phosphorylation Deficiency	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	Combined Oxidative Phosphorylation Deficiency	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20	Combined Oxidative Phosphorylation Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Complete atrioventricular block	Complete Atrioventricular Block	BEFREE	25404243		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	31064326	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	GWASDB_DG	17632545		★☆☆☆☆ Found in Text Mining only
Dwarfism Pituitary	Pituitary dwarfism	Pubtator	29137650	Associate	★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	21708121, 23433712, 24827421, 25058219, 27290639, 27502409		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	31064326		★☆☆☆☆ Found in Text Mining only
Epilepsia Partialis Continua	Epilepsia Partialis Continua	BEFREE	29314548		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	24827421, 29137650, 29221463		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	24827421, 29137650	Associate	★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	30755602, 31623496		★☆☆☆☆ Found in Text Mining only
Fatigue Syndrome Chronic	Fatigue syndrome	Pubtator	34403736	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	29314548		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	29137650	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	31529142		★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	30458719		★☆☆☆☆ Found in Text Mining only
Hypertrophic obstructive cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	30458719		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	BEFREE	29137650, 29221463		★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	29137650	Associate	★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	BEFREE	27502409		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	29137650	Associate	★☆☆☆☆ Found in Text Mining only
Kearns-Sayre syndrome	Kearns Sayre Syndrome	BEFREE	30925032		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	36634566	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20503108		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	24827421		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	24827421	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial cardiomyopathy	Mitochondrial Cardiomyopathy	BEFREE	30458719		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	24827421, 25058219, 29314548, 30458719	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	25058219, 29314548, 30458719, 31529142		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	BEFREE	24827421, 27502409, 29314548		★☆☆☆☆ Found in Text Mining only
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	24827421, 29314548	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial encephalopathy	Mitochondrial encephalopathy	Pubtator	24827421, 31064326	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial encephalopathy	Mitochondrial encephalopathy	BEFREE	31064326		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	21708121, 23433712, 24827421, 25058219, 27290639, 27502409		★☆☆☆☆ Found in Text Mining only
Myasthenia Gravis	Myasthenia Gravis	GWASDB_DG	23055271		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	31487037	Associate	★☆☆☆☆ Found in Text Mining only
Persistent Fetal Circulation Syndrome	Persistent Fetal Circulation	BEFREE	30458719		★☆☆☆☆ Found in Text Mining only
Psychomotor Disorders	Psychiatric disorders	Pubtator	29314548, 31064326	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	GWASDB_DG	17804836, 19503088		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	BEFREE	28238293		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	29314548	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of lung	Lung carcinoma	GWASCAT_DG	28604730		★☆☆☆☆ Found in Text Mining only