YARS1 (tyrosyl-tRNA synthetase 1)

Gene

• Entrez ID: 8565
• Gene name: Tyrosyl-tRNA synthetase 1
• Gene symbol: YARS1
• Synonyms (NCBI Gene): CMTDIC, IMNEPD2, TYRRS, YARS, YRS, YTS
• Chromosome: 1
• Chromosome location: 1p35.1
• 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
rs121908833	C>T	Pathogenic, uncertain-significance	5 prime UTR variant, missense variant, intron variant, coding sequence variant
rs121908834	C>G,T	Pathogenic-likely-pathogenic, pathogenic, uncertain-significance	5 prime UTR variant, missense variant, coding sequence variant
rs149620809	T>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs201272488	C>G	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs774466323	A>G	Pathogenic, uncertain-significance	Coding sequence variant, intron variant, missense variant, 5 prime UTR variant
rs780528629	C>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, 5 prime UTR variant
rs780574093	G>A,C	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, synonymous variant
rs786200893	GCTTTACCACCT>-	Pathogenic	Coding sequence variant, inframe deletion, 5 prime UTR variant
rs786204003	TC>AT	Pathogenic	Missense variant, coding sequence variant, intron variant, 5 prime UTR variant
rs786205442	G>T	Likely-pathogenic	Missense variant, coding sequence variant
rs965890133	G>C,T	Pathogenic	5 prime UTR variant, coding sequence variant, stop gained, intron 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	HDA	22658674
GO:0003723	Function	RNA binding	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004831	Function	Tyrosine-tRNA ligase activity	IBA
GO:0004831	Function	Tyrosine-tRNA ligase activity	IDA	22291016, 25533949
GO:0004831	Function	Tyrosine-tRNA ligase activity	IEA
GO:0004831	Function	Tyrosine-tRNA ligase activity	TAS	9162081
GO:0005153	Function	Interleukin-8 receptor binding	TAS	10102815
GO:0005515	Function	Protein binding	IPI	24965446, 25533949, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005615	Component	Extracellular space	TAS	10102815
GO:0005634	Component	Nucleus	IDA	22291016, 25533949
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	25533949
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	9162081
GO:0005829	Component	Cytosol	IDA	22291016
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:0006437	Process	Tyrosyl-tRNA aminoacylation	IDA	25533949
GO:0006437	Process	Tyrosyl-tRNA aminoacylation	IDA	25533949
GO:0006437	Process	Tyrosyl-tRNA aminoacylation	IEA
GO:0006437	Process	Tyrosyl-tRNA aminoacylation	TAS	9162081
GO:0006915	Process	Apoptotic process	TAS	10102815
GO:0006950	Process	Response to stress	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0016874	Function	Ligase activity	IEA
GO:0036094	Function	Small molecule binding	IDA	25533949
GO:0042594	Process	Response to starvation	IDA	25533949
GO:0070212	Process	Protein poly-ADP-ribosylation	IDA	25043379

Other IDs

• MIM: 603623
• HGNC: 12840
• e!Ensembl: ENSG00000134684

Protein

• UniProt ID: P54577
• Protein name: Tyrosine--tRNA ligase, cytoplasmic (EC 6.1.1.1) (Tyrosyl-tRNA synthetase) (TyrRS) [Cleaved into: Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed]
• Protein function: Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts
• PDB: 1N3L, 1NTG, 1Q11, 4Q93, 4QBT, 5THH, 5THL, 7ROU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00579	tRNA-synt_1b	31 → 322	tRNA synthetases class I (W and Y)	Family
  PF01588	tRNA_bind	370 → 466	Putative tRNA binding domain	Domain

• Sequence:

  MGDAPSPEEKLHLITRNLQEVLGEEKLKEILKERELKIYWGTATTGKPHVAYFVPMSKIA
  DFLKAGCEVTILFADLHAYLDNMKAPWELLELRVSYYENVIKAMLESIGVPLEKLKFIKG
  TDYQLSKEYTLDVYRLSSVVTQHDSKKAGAEVVKQVEHPLLSGLLYPGLQALDEEYLKVD
  AQFGGIDQRKIFTFAEKYLPALGYSKRVHLMNPMVPGLTGSKMSSSEEESKIDLLDRKED
  VKKKLKKAFCEPGNVENNGVLSFIKHVLFPLKSEFVILRDEKWGGNKTYTAYVDLEKDFA
  AEVVHPGDLKNSVEVALNKLLDPIREKFNTPALKKLASAAYPDPSKQKPMAKGPAKNSEP
  EEVIPSRLDIRVGKIITVEKHPDADSLYVEKIDVGEAEPRTVVSGLVQFVPKEELQDRLV
  VVLCNLKPQKMRGVESQGMLLCASIEGINRQVEPLDPPAGSAPGEHVFVKGYEKGQPDEE
  LKPKKKVFEKLQADFKISEECIAQWKQTNFMTKLGSISCKSLKGGNIS

• Sequence length: 528

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
Charcot-Marie-Tooth disease	Pathogenic; Likely pathogenic	rs121908833, rs121908834	RCV000789620 RCV000789621	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Charcot-Marie-Tooth disease dominant intermediate C	Pathogenic; Likely pathogenic	rs786204003, rs121908833, rs121908834, rs786200893, rs376054085, rs1279417718	RCV000167583 RCV000006565 RCV000006566 RCV000006567 RCV000235060 RCV000687751 RCV000819906	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Corpus callosum, agenesis of	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hepatic steatosis	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset	Likely pathogenic	rs1638772305, rs2148614935	RCV002274456 RCV002274457	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2	Likely pathogenic; Pathogenic	rs121908834, rs1553123702, rs1553122256, rs376054085, rs1279417718, rs1653248260	RCV003328123 RCV000515957 RCV000516098 RCV002226737 RCV001533215 RCV001533214	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary amenorrhea	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
recessive ARS-related multisystem disease	Likely pathogenic; Pathogenic	rs376054085	RCV001264808	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinal degeneration	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Severe hearing impairment	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT INTERMEDIATE CHARCOT-MARIE-TOOTH DISEASE TYPE C	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE C	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth, Intermediate	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLESTATIC LIVER DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERINSULINEMIC HYPOGLYCEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEUKODYSTROPHY, METACHROMATIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER FAILURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental delay	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
YARS1-related disorder	Likely benign; Benign; Uncertain significance; 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
Asthma	Asthma	BEFREE	30145544		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	30774629		★☆☆☆☆ Found in Text Mining only
Autosomal dominant intermediate Charcot-Marie-Tooth disease type C	Charcot-Marie-Tooth Disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33239070	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	35306563	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	16429158, 17545306, 21732632, 24807208, 26138142, 27633801, 31501329, 31695036		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Charcot-Marie-Tooth Disease, Dominant Intermediate C	Charcot-Marie-Tooth Disease	CLINVAR_DG	14606043, 16429158, 19561293, 26138142, 26257172, 26975778		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth Disease, Dominant Intermediate C	Charcot-Marie-Tooth Disease	ORPHANET_DG	16429158		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth Disease, Dominant Intermediate C	Charcot-Marie-Tooth Disease	UNIPROT_DG	16429158		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth Disease, Dominant Intermediate C	Charcot-Marie-Tooth Disease	GENOMICS_ENGLAND_DG	16429158, 19561293		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth Disease, Dominant Intermediate C	Charcot-Marie-Tooth Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic Disease	Chronic disease	Pubtator	30304524	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	36154909	Associate	★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	31685661	Associate	★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	30304524	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24510587		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of testis	Malignant Neoplasm Of Testis	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
Malignant Testicular Germ Cell Tumor	Malignant testicular germ cell tumor	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	31054264		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	30214071	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	24344687	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	33239070	Stimulate	★☆☆☆☆ Found in Text Mining only
Myopathy with lactic acidosis and sideroblastic anemia	Mitochondrial myopathy with sideroblastic anemia	Pubtator	24344687	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	21052085		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	21052085	Associate	★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	16429158		★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular disease	Pubtator	36307205	Associate	★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	16429158, 24807208, 28469666		★☆☆☆☆ Found in Text Mining only
Nystagmus Pathologic	Nystagmus	Pubtator	30304524	Associate	★☆☆☆☆ Found in Text Mining only
Optic Atrophy Hereditary Leber	Leber hereditary optic neuropathy	Pubtator	34156427	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	21384131, 27633801, 30304524		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	28531329, 36307205	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	21384131, 27633801, 30304524		★☆☆☆☆ Found in Text Mining only
Porphyrias	Porphyria	Pubtator	24894379	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	10533904		★☆☆☆☆ Found in Text Mining only
Proteinuria	Proteinuria	Pubtator	30304524	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31315917	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of mouth	Oral cavity carcinoma	BEFREE	31315917		★☆☆☆☆ Found in Text Mining only
T-Cell Lymphoma	T-Cell Lymphoma	BEFREE	26499190		★☆☆☆☆ Found in Text Mining only