TARS1 (threonyl-tRNA synthetase 1)

Gene

• Entrez ID: 6897
• Gene name: Threonyl-tRNA synthetase 1
• Gene symbol: TARS1
• Synonyms (NCBI Gene): TARS, TTD7, ThrRS
• Chromosome: 5
• Chromosome location: 5p13.3
• 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
rs749888012	C>T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs1579584983	T>C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1579585658	A>G	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0003723	Function	RNA binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004829	Function	Threonine-tRNA ligase activity	IBA
GO:0004829	Function	Threonine-tRNA ligase activity	IDA	25824639
GO:0004829	Function	Threonine-tRNA ligase activity	IEA
GO:0004829	Function	Threonine-tRNA ligase activity	ISS
GO:0005515	Function	Protein binding	IPI	25416956, 32296183, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	IMP	25824639
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
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	IDA	25824639
GO:0006435	Process	Threonyl-tRNA aminoacylation	IEA
GO:0006435	Process	Threonyl-tRNA aminoacylation	ISS
GO:0008270	Function	Zinc ion binding	IDA	25824639
GO:0016874	Function	Ligase activity	IEA
GO:0042802	Function	Identical protein binding	IPI	25824639
GO:0043039	Process	TRNA aminoacylation	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337

Other IDs

• MIM: 187790
• HGNC: 11572
• e!Ensembl: ENSG00000113407

Protein

• UniProt ID: P26639
• Protein name: Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 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) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charg
• PDB: 1WWT, 4HWT, 4P3N, 4TTV, 5XLN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02824	TGS	83 → 143	TGS domain	Domain
  PF07973	tRNA_SAD	249 → 298	Threonyl and Alanyl tRNA synthetase second additional domain	Domain
  PF00587	tRNA-synt_2b	397 → 608	tRNA synthetase class II core domain (G, H, P, S and T)	Domain
  PF03129	HGTP_anticodon	620 → 711	Anticodon binding domain	Domain

• Sequence:

  MFEEKASSPSGKMGGEEKPIGAGEEKQKEGGKKKNKEGSGDGGRAELNPWPEYIYTRLEM
  YNILKAEHDSILAEKAEKDSKPIKVTLPDGKQVDAESWKTTPYQIACGISQGLADNTVIA
  KVNNVVWDLDRPLEEDCTLELLKFEDEEAQAVYWHSSAHIMGEAMERVYGGCLCYGPPIE
  NGFYYDMYLEEGGVSSNDFSSLEALCKKIIKEKQAFERLEVKKETLLAMFKYNKFKCRIL
  NEKVNTPTTTVYRCGPLIDLCRGPHVRHTGKIKALKIHKNSSTYWEGKADMETLQRIYGI
  SFPDPKMLKEWEKFQEEAKNRDHRKIGRDQELYFFHELSPGSCFFLPKGAYIYNALIEFI
  RSEYRKRGFQEVVTPNIFNSRLWMTSGHWQHYSENMFSFEVEKELFALKPMNCPGHCLMF
  DHRPRSWRELPLRLADFGVLHRNELSGALTGLTRVRRFQQDDAHIFCAMEQIEDEIKGCL
  DFLRTVYSVFGFSFKLNLSTRPEKFLGDIEVWDQAEKQLENSLNEFGEKWELNSGDGAFY
  GPKIDIQIKDAIGRYHQCATIQLDFQLPIRFNLTYVSHDGDDKKRPVIVHRAILGSVERM
  IAILTENYGGKWPFWLSPRQVMVVPVGPTCDEYAQKVRQQFHDAKFMADIDLDPGCTLNK
  KIRNAQLAQYNFILVVGEKEKISGTVNIRTRDNKVHGERTISETIERLQQLKEFRSKQAE
  EEF

• Sequence length: 723

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
Trichothiodystrophy 7, nonphotosensitive	Pathogenic	rs749888012, rs1579585658, rs1579584983	RCV000850111 RCV000850112 RCV000850113	★★★★☆ 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
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CYSTIC FIBROSIS ASSOCIATED MECONIUM ILEUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOSITIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATIC CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TARS1-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRICHOTHIODYSTROPHY	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRICHOTHIODYSTROPHY SYNDROMES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult T-Cell Lymphoma/Leukemia	T-Cell Lymphoma/Leukemia	BEFREE	2999237, 6323614		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune disease	Pubtator	23425968	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	34868337, 38358781	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	25163878	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Congenital Nonbullous Ichthyosiform Erythroderma	Congenital Nonbullous Ichthyosiform Erythroderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	36881401	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic Inflammatory Myopathies	Inflammatory Myopathy	BEFREE	16609350		★☆☆☆☆ Found in Text Mining only
Idiopathic Inflammatory Myopathies	Inflammatory Myopathy	CTD_human_DG	23425968		★☆☆☆☆ Found in Text Mining only
Leukemia, T-Cell	T-cell leukemia	BEFREE	6323614		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Myositis	Myositis	Pubtator	16609350, 23425968	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myositis	Myositis	CTD_human_DG	23425968		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myositis, Focal	Myositis	CTD_human_DG	23425968		★☆☆☆☆ Found in Text Mining only
Myositis, Proliferative	Myositis	CTD_human_DG	23425968		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	25163878		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	25163878	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	29328069	Associate	★☆☆☆☆ Found in Text Mining only
Phrynoderma	Phrynoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	35715770	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34159625	Stimulate	★☆☆☆☆ Found in Text Mining only
Trichothiodystrophy	Trichothiodystrophy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	18559093	Associate	★☆☆☆☆ Found in Text Mining only