TARS2 (threonyl-tRNA synthetase 2, mitochondrial)

Gene

• Entrez ID: 80222
• Gene name: Threonyl-tRNA synthetase 2, mitochondrial
• Gene symbol: TARS2
• Synonyms (NCBI Gene): COXPD21, TARSL1, thrRS
• Chromosome: 1
• Chromosome location: 1q21.2
• Summary: This gene encodes a member of the class-II aminoacyl-tRNA synthetase family. The encoded protein is a mitochondrial aminoacyl-tRNA synthetase. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromo

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs367870620	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, stop gained, intron variant
rs587777593	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT041757	hsa-miR-484	CLASH	23622248
MIRT041757	hsa-miR-484	CLASH	23622248
MIRT2123559	hsa-miR-2278	CLIP-seq
MIRT2123560	hsa-miR-3166	CLIP-seq
MIRT2123561	hsa-miR-4433	CLIP-seq
MIRT2123562	hsa-miR-4459	CLIP-seq
MIRT2123563	hsa-miR-4468	CLIP-seq
MIRT2123564	hsa-miR-4753-3p	CLIP-seq
MIRT2123565	hsa-miR-4768-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IDA	26811336
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004829	Function	Threonine-tRNA ligase activity	IBA
GO:0004829	Function	Threonine-tRNA ligase activity	IDA	26811336
GO:0004829	Function	Threonine-tRNA ligase activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006435	Process	Threonyl-tRNA aminoacylation	IBA
GO:0006435	Process	Threonyl-tRNA aminoacylation	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	26811336
GO:0043039	Process	TRNA aminoacylation	IEA
GO:0070159	Process	Mitochondrial threonyl-tRNA aminoacylation	TAS	15779907
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 612805
• HGNC: 30740
• e!Ensembl: ENSG00000143374

Protein

• UniProt ID: Q9BW92
• Protein name: Threonine--tRNA ligase, mitochondrial (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase-like 1)
• Protein function: Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02824	TGS	61 → 121	TGS domain	Domain
  PF07973	tRNA_SAD	228 → 277	Threonyl and Alanyl tRNA synthetase second additional domain	Domain
  PF00587	tRNA-synt_2b	394 → 603	tRNA synthetase class II core domain (G, H, P, S and T)	Domain
  PF03129	HGTP_anticodon	615 → 706	Anticodon binding domain	Domain

• Sequence:

  MALYQRWRCLRLQGLQACRLHTAVVSTPPRWLAERLGLFEELWAAQVKRLASMAQKEPRT
  IKISLPGGQKIDAVAWNTTPYQLARQISSTLADTAVAAQVNGEPYDLERPLETDSDLRFL
  TFDSPEGKAVFWHSSTHVLGAAAEQFLGAVLCRGPSTEYGFYHDFFLGKERTIRGSELPV
  LERICQELTAAARPFRRLEASRDQLRQLFKDNPFKLHLIEEKVTGPTATVYGCGTLVDLC
  QGPHLRHTGQIGGLKLLSNSSSLWRSSGAPETLQRVSGISFPTTELLRVWEAWREEAELR
  DHRRIGKEQELFFFHELSPGSCFFLPRGTRVYNALVAFIRAEYAHRGFSEVKTPTLFSTK
  LWEQSGHWEHYQEDMFAVQPPGSDRPPSSQSDDSTRHITDTLALKPMNCPAHCLMFAHRP
  RSWRELPLRLADFGALHRAEASGGLGGLTRLRCFQQDDAHIFCTTDQLEAEIQSCLDFLR
  SVYAVLGFSFRLALSTRPSGFLGDPCLWDQAEQVLKQALKEFGEPWDLNSGDGAFYGPKI
  DVHLHDALGRPHQCGTIQLDFQLPLRFDLQYKGQAGALERPVLIHRAVLGSVERLLGVLA
  ESCGGKWPLWLSPFQVVVIPVGSEQEEYAKEAQQSLRAAGLVSDLDADSGLTLSRRIRRA
  QLAHYNFQFVVGQKEQSKRTVNIRTRDNRRLGEWDLPEAVQRLVELQNTRVPNAEEIF

• Sequence length: 718

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
Combined oxidative phosphorylation defect type 21	Likely pathogenic; Pathogenic	rs2102494691, rs2102510285, rs758088548, rs756855066, rs587777593, rs587777594, rs1322913410, rs2526263331, rs781477512, rs367984492, rs778133443	RCV001527459 RCV001527461 RCV001837554 RCV001837555 RCV000132557 RCV000132558 RCV003315457 RCV003315459 RCV003315461 RCV003315462 RCV003315463	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	—	CTD, HPO CTD, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital blindness	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Failure to thrive	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	CTD, ClinGen	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic hemiparesis	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TARS2-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	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
Brain Diseases	Brain disease	Pubtator	39394138	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	37956648	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Ischemic stroke	Pubtator	35862251	Associate	★☆☆☆☆ Found in Text Mining only
Combined oxidative phosphorylation defect type 21	Combined Oxidative Phosphorylation Deficiency	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Combined Oxidative Phosphorylation Deficiency 1	Combined oxidative phosphorylation deficiency	Pubtator	33153448	Associate	★☆☆☆☆ Found in Text Mining only
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	Combined Oxidative Phosphorylation Deficiency	UNIPROT_DG	24827421, 26811336		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	Combined Oxidative Phosphorylation Deficiency	ORPHANET_DG	24827421		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	Combined Oxidative Phosphorylation Deficiency	GENOMICS_ENGLAND_DG	24827421		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	Combined Oxidative Phosphorylation Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 21	Combined Oxidative Phosphorylation Deficiency	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital Abnormalities	Congenital abnormalities	Pubtator	39394138	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	24827421		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	24827421		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	39394138	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic Inflammatory Myopathies	Inflammatory Myopathy	BEFREE	16609350		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	24827421		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	24827421	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	BEFREE	24827421, 26811336		★☆☆☆☆ Found in Text Mining only
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	24827421, 26811336, 33153448, 39394138	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial encephalopathy	Mitochondrial encephalopathy	Pubtator	24827421	Associate	★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Psychomotor Disorders	Psychiatric disorders	Pubtator	24827421, 39394138	Associate	★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only