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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Charcot-Marie-Tooth disease	Pathogenic; Likely pathogenic	rs121908833, rs121908834	RCV000789620 RCV000789621
Charcot-Marie-Tooth disease dominant intermediate C	Pathogenic; Likely pathogenic	rs786204003, rs121908833, rs121908834, rs786200893, rs376054085, rs1279417718	RCV000167583 RCV000006565 RCV000006566 RCV000006567 RCV000235060 RCV000687751 RCV000819906
Corpus callosum, agenesis of	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417
Hepatic steatosis	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset	Likely pathogenic	rs1638772305, rs2148614935	RCV002274456 RCV002274457
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2	Likely pathogenic; Pathogenic	rs121908834, rs1553123702, rs1553122256, rs376054085, rs1279417718, rs1653248260	RCV003328123 RCV000515957 RCV000516098 RCV002226737 RCV001533215 RCV001533214
Primary amenorrhea	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417
recessive ARS-related multisystem disease	Likely pathogenic; Pathogenic	rs376054085	RCV001264808
Retinal degeneration	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417
Severe hearing impairment	Likely pathogenic; Pathogenic	rs1653248260	RCV001291417

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Charcot-Marie-Tooth, Intermediate	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	rs201272488, rs372462149, rs1057515512, rs762551221, rs142185532	RCV000377682 RCV000405036 RCV000389284 RCV000343052 RCV000292800
Hepatocellular carcinoma	Likely benign	rs76862302	RCV005929989
Neurodevelopmental delay	Conflicting classifications of pathogenicity	rs1360212575, rs774466323	RCV002274437 RCV002274090
See cases	Uncertain significance	rs1653652616	RCV001196090
Thyroid cancer, nonmedullary, 1	Uncertain significance	rs763115155	RCV005934665
YARS1-related disorder	Likely benign; Benign; Uncertain significance; Conflicting classifications of pathogenicity	rs779620591, rs372082251, rs76862302, rs751440666, rs151227410, rs763115155, rs949689567, rs2523373241, rs2523359284, rs149620809, rs61737106, rs149741618	RCV003973300 RCV003938868 RCV003973354 RCV003927858 RCV003949992 RCV004758284 RCV003921493 RCV003982574 RCV003934303 RCV003915550 RCV003905389 RCV003965661

Associations from Text Mining
Disease Name	Relationship Type	References
AIDS Associated Nephropathy	Associate	30304524
Breast Neoplasms	Associate	33239070
Carcinoma Hepatocellular	Associate	35306563
Charcot Marie Tooth Disease	Associate	17545306, 31501329
Chronic Disease	Associate	30304524
Colorectal Neoplasms	Associate	36154909
Deafness	Associate	31685661
Disease	Associate	30304524
Liver Diseases	Associate	30304524
Microcephaly	Associate	30214071
Mitochondrial Diseases	Associate	24344687
Mitochondrial Diseases	Stimulate	33239070
Muscular Diseases	Associate	24344687
Myopathy with lactic acidosis and sideroblastic anemia	Associate	24344687
Nasopharyngeal Carcinoma	Associate	21052085
Neuromuscular Diseases	Associate	36307205
Noninsulin dependent diabetes mellitus with deafness	Associate	31685661
Nystagmus Pathologic	Associate	30304524
Optic Atrophy Hereditary Leber	Associate	34156427
Peripheral Nervous System Diseases	Associate	28531329, 36307205
Porphyrias	Associate	24894379
Proteinuria	Associate	30304524
Squamous Cell Carcinoma of Head and Neck	Associate	31315917
X linked sideroblastic anemia	Associate	24344687