WARS1 (tryptophanyl-tRNA synthetase 1)

Gene

• Entrez ID: 7453
• Gene name: Tryptophanyl-tRNA synthetase 1
• Gene symbol: WARS1
• Synonyms (NCBI Gene): GAMMA-2, HMN9, HMND9, IFI53, IFP53, NEDMSBA, WARS
• Chromosome: 14
• Chromosome location: 14q32.2
• 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
rs770003315	T>A,C	Pathogenic	Coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001525	Process	Angiogenesis	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004830	Function	Tryptophan-tRNA ligase activity	IBA
GO:0004830	Function	Tryptophan-tRNA ligase activity	IEA
GO:0004830	Function	Tryptophan-tRNA ligase activity	IMP	28369220
GO:0004830	Function	Tryptophan-tRNA ligase activity	NAS	8496617
GO:0005515	Function	Protein binding	IPI	15628863, 20010843, 21044950, 22504299, 39232006
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005634	Component	Nucleus	IDA	22504299
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	1761529, 16130169
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	IEA
GO:0006412	Process	Translation	TAS	1761529
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006436	Process	Tryptophanyl-tRNA aminoacylation	IBA
GO:0006436	Process	Tryptophanyl-tRNA aminoacylation	IEA
GO:0006436	Process	Tryptophanyl-tRNA aminoacylation	NAS	8496617
GO:0006436	Process	Tryptophanyl-tRNA aminoacylation	TAS	1761529
GO:0006469	Process	Negative regulation of protein kinase activity	IDA	22504299
GO:0008285	Process	Negative regulation of cell population proliferation	TAS	1761529
GO:0010628	Process	Positive regulation of gene expression	IDA	22504299
GO:0016874	Function	Ligase activity	IEA
GO:0019210	Function	Kinase inhibitor activity	IDA	22504299
GO:0019901	Function	Protein kinase binding	IPI	22504299
GO:0019904	Function	Protein domain specific binding	IPI	22504299
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IMP	22504299
GO:0032991	Component	Protein-containing complex	IMP	22504299
GO:0042803	Function	Protein homodimerization activity	IDA	22504299, 28369220
GO:0045765	Process	Regulation of angiogenesis	IDA	11773625, 11773626
GO:0070062	Component	Extracellular exosome	HDA	20458337, 23533145

Other IDs

• MIM: 191050
• HGNC: 12729
• e!Ensembl: ENSG00000140105

Protein

• UniProt ID: P23381
• Protein name: Tryptophan--tRNA ligase, cytoplasmic (EC 6.1.1.2) (Interferon-induced protein 53) (IFP53) (Tryptophanyl-tRNA synthetase) (TrpRS) (hWRS) [Cleaved into: T1-TrpRS; T2-TrpRS]
• Protein function: Catalyzes the attachment of tryptophan to tRNA(Trp) in a two-step reaction: tryptophan is first activated by ATP to form Trp-AMP and then transferred to the acceptor end of the tRNA(Trp). {ECO:0000269|PubMed:1373391, ECO:0000269|PubMed:1761529,
• PDB: 1O5T, 1R6T, 1R6U, 1ULH, 2AKE, 2AZX, 2DR2, 2QUH, 2QUI, 2QUJ, 2QUK, 5UJI, 5UJJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00458	WHEP-TRS	12 → 64	WHEP-TRS domain	Domain
  PF00579	tRNA-synt_1b	151 → 443	tRNA synthetases class I (W and Y)	Family

• Sequence:

  MPNSEPASLLELFNSIATQGELVRSLKAGNASKDEIDSAVKMLVSLKMSYKAAAGEDYKA
  DCPPGNPAPTSNHGPDATEAEEDFVDPWTVQTSSAKGIDYDKLIVRFGSSKIDKELINRI
  ERATGQRPHHFLRRGIFFSHRDMNQVLDAYENKKPFYLYTGRGPSSEAMHVGHLIPFIFT
  KWLQDVFNVPLVIQMTDDEKYLWKDLTLDQAYSYAVENAKDIIACGFDINKTFIFSDLDY
  MGMSSGFYKNVVKIQKHVTFNQVKGIFGFTDSDCIGKISFPAIQAAPSFSNSFPQIFRDR
  TDIQCLIPCAIDQDPYFRMTRDVAPRIGYPKPALLHSTFFPALQGAQTKMSASDPNSSIF
  LTDTAKQIKTKVNKHAFSGGRDTIEEHRQFGGNCDVDVSFMYLTFFLEDDDKLEQIRKDY
  TSGAMLTGELKKALIEVLQPLIAEHQARRKEVTDEIVKEFMTPRKLSFDFQ

• Sequence length: 471

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
Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities	Pathogenic; Likely pathogenic	rs2549306131, rs550196955, rs2139927654	RCV003223372 RCV003223373 RCV003990819	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE PRIMARY MICROCEPHALY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental delay	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DISTAL HEREDITARY MOTOR NEUROPATHY	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISTAL SPINAL MUSCULAR ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 9	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuronopathy, distal hereditary motor, type 9	Benign; Uncertain significance; Conflicting classifications of pathogenicity; no classifications from unflagged records	ClinVar ClinVar, GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID CANCER, PAPILLARY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WARS1-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	29489025		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	29485232	Associate	★☆☆☆☆ Found in Text Mining only
Arrhythmias Cardiac	Cardiac arrhythmias	Pubtator	12747836	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	37967346	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	9848077	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	33179081	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	22546478	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	23741347	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Ischemic stroke	Pubtator	39542148	Associate	★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	31069783		★☆☆☆☆ Found in Text Mining only
Chronic granulomatous disease	Granulomatous Disease	BEFREE	30260027		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	30293546		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	19383890, 25206290, 37794510	Associate	★☆☆☆☆ Found in Text Mining only
Conduct Disorder	Conduct disorder	Pubtator	23741347	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Gestational	Gestational diabetes	Pubtator	36313769	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	29139617		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	23856170		★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	23856170		★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	38274229	Associate	★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	31834547		★☆☆☆☆ Found in Text Mining only
Dyskinesias	Dyskinesia	Pubtator	22546478	Associate	★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa Junctional	Junctional epidermolysis bullosa	Pubtator	9085255, 9326326	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	23257655, 27493204	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy Absence	Absence epilepsy	Pubtator	19846749	Associate	★☆☆☆☆ Found in Text Mining only
Familial Nonmedullary Thyroid Cancer	Thyroid cancer	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	BEFREE	28871595		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	29139617		★☆☆☆☆ Found in Text Mining only
Granulomatous Disease Chronic	Granulomatous disease	Pubtator	30260027	Associate	★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	BEFREE	19363598		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	12747836	Associate	★☆☆☆☆ Found in Text Mining only
Hypertrophy	Hypertrophy	Pubtator	23741347	Associate	★☆☆☆☆ Found in Text Mining only
IgA Deficiency	Selective immunoglobulin a deficiency	Pubtator	19153537	Associate	★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	30293546		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	29120065	Associate	★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	BEFREE	29139617		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	23026198	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	21926542		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23957735, 31033497		★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	38247871	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	19363598		★☆☆☆☆ Found in Text Mining only
Microvascular Angina	Microvascular angina	Pubtator	23741347	Associate	★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth neoplasm	Pubtator	26110569	Stimulate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	9233573	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	15939065		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21926542, 23957735, 26110569, 28871595, 29489025, 31033497, 7814143		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	16616781		★☆☆☆☆ Found in Text Mining only
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IX	Neuronopathy	UNIPROT_DG	28369220		★☆☆☆☆ Found in Text Mining only
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IX	Neuronopathy	GENOMICS_ENGLAND_DG	28369220		★☆☆☆☆ Found in Text Mining only
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IX	Neuronopathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	28369220		★☆☆☆☆ Found in Text Mining only
Nonmedullary Thyroid Carcinoma	Nonmedullary thyroid carcinoma	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Osteopetrosis	Osteopetrosis	Pubtator	24336069	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	33754909	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	21926542		★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	CTD_human_DG	28030816		★☆☆☆☆ Found in Text Mining only
Parkinson Disease Secondary	Secondary parkinson disease	Pubtator	29120065	Associate	★☆☆☆☆ Found in Text Mining only
Parkinsonian Disorders	Parkinson Disease	BEFREE	29120065		★☆☆☆☆ Found in Text Mining only
Peripheral motor neuropathy	Motor nerve neuritis	BEFREE	28369220, 31069783		★☆☆☆☆ Found in Text Mining only
Proteinuria	Proteinuria	Pubtator	9233573	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	24515434, 30714436		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	Pubtator	26241350	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Seizures	Seizures	Pubtator	23257655	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	26110569, 31315917	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	31033497	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	26209610		★☆☆☆☆ Found in Text Mining only
Uveal melanoma	Uveal Melanoma	BEFREE	31694485		★★☆☆☆ Found in Text Mining + Unknown/Other Associations