IARS1 (isoleucyl-tRNA synthetase 1)

Gene

• Entrez ID: 3376
• Gene name: Isoleucyl-tRNA synthetase 1
• Gene symbol: IARS1
• Synonyms (NCBI Gene): GRIDHH, IARS, ILERS, ILRS, IRS, PRO0785
• Chromosome: 9
• Chromosome location: 9q22.31
• 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
rs34737051	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant
rs747311061	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant, intron variant
rs764500338	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs886037873	A>T	Pathogenic	Coding sequence variant, missense variant, intron variant, non coding transcript variant
rs886037874	G>A	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs886037875	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs886037876	A>C	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs886037877	T>C	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs1057520159	CT>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1554728327	A>G	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1587725422	T>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1587880332	GTAG>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0001649	Process	Osteoblast differentiation	HDA	16210410
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004822	Function	Isoleucine-tRNA ligase activity	IBA
GO:0004822	Function	Isoleucine-tRNA ligase activity	IDA	8052601
GO:0004822	Function	Isoleucine-tRNA ligase activity	IEA
GO:0004822	Function	Isoleucine-tRNA ligase activity	TAS
GO:0005515	Function	Protein binding	IPI	9556618, 10913161, 11142386, 30021884, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	8052601, 22424946
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	7721108
GO:0005829	Component	Cytosol	IDA	19289464
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IBA
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IDA	8052601
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IDA	8052601
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IEA
GO:0016020	Component	Membrane	HDA	16210410, 19946888
GO:0016874	Function	Ligase activity	IEA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0051020	Function	GTPase binding	IPI	24337748
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 600709
• HGNC: 5330
• e!Ensembl: ENSG00000196305

Protein

• UniProt ID: P41252
• Protein name: Isoleucine--tRNA ligase, cytoplasmic (EC 6.1.1.5) (Isoleucyl-tRNA synthetase) (IRS) (IleRS)
• Protein function: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	17 → 639	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	693 → 852	Anticodon-binding domain of tRNA ligase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in liver and muscle (at protein level). {ECO:0000269|PubMed:27426735}.
• Sequence:

  MLQQVPENINFPAEEEKILEFWTEFNCFQECLKQSKHKPKFTFYDGPPFATGLPHYGHIL
  AGTIKDIVTRYAHQSGFHVDRRFGWDCHGLPVEYEIDKTLGIRGPEDVAKMGITEYNNQC
  RAIVMRYSAEWKSTVSRLGRWIDFDNDYKTLYPQFMESVWWVFKQLYDKGLVYRGVKVMP
  FSTACNTPLSNFESHQNYKDVQDPSVFVTFPLEEDETVSLVAWTTTPWTLPSNLAVCVNP
  EMQYVKIKDVARGRLLILMEARLSALYKLESDYEILERFPGAYLKGKKYRPLFDYFLKCK
  ENGAFTVLVDNYVKEEEGTGVVHQAPYFGAEDYRVCMDFNIIRKDSLPVCPVDASGCFTT
  EVTDFAGQYVKDADKSIIRTLKEQGRLLVATTFTHSYPFCWRSDTPLIYKAVPSWFVRVE
  NMVDQLLRNNDLCYWVPELVREKRFGNWLKDARDWTISRNRYWGTPIPLWVSDDFEEVVC
  IGSVAELEELSGAKISDLHRESVDHLTIPSRCGKGSLHRISEVFDCWFESGSMPYAQVHY
  PFENKREFEDAFPADFIAEGIDQTRGWFYTLLVLATALFGQPPFKNVIVNGLVLASDGQK
  MSKRKKNYPDPVSIIQKYGADALRLYLINSPVVRAENLRFKEEGVRDVLKDVLLPWYNAY
  RFLIQNVLRLQKEEEIEFLYNENTVRESPNITDRWILSFMQSLIGFFETEMAAYRLYTVV
  PRLVKFVDILTNWYVRMNRRRLKGENGMEDCVMALETLFSVLLSLCRLMAPYTPFLTELM
  YQNLKVLIDPVSVQDKDTLSIHYLMLPRVREELIDKKTESAVSQMQSVIELGRVIRDRKT
  IPIKYPLKEIVVIHQDPEALKDIKSLEKYIIEELNVRKVTLSTDKNKYGIRLRAEPDHMV
  LGKRLKGAFKAVMTSIKQLSSEELEQFQKTGTIVVEGHELHDEDIRLMYTFDQATGGTAQ
  FEAHSDAQALVLLDVTPDQSMVDEGMAREVINRIQKLRKKCNLVPTDEITVYYKAKSEGT
  YLNSVIESHTEFIFTTIKAPLKPYPVSPSDKVLIQEKTQLKGSELEITLTRGSSLPGPAC
  AYVNLNICANGSEQGGVLLLENPKGDNRLDLLKLKSVVTSIFGVKNTELAVFHDETEIQN
  QTDLLSLSGKTLCVTAGSAPSLINSSSTLLCQYINLQLLNAKPQECLMGTVGTLLLENPL
  GQNGLTHQGLLYEAAKVFGLRSRKLKLFLNETQTQEITEDIPVKTLNMKTVYVSVLPTTA
  DF

• Sequence length: 1262

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Global developmental delay	Likely pathogenic	rs2133977803	RCV001728188
Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy	Pathogenic	rs765771535, rs764500338, rs886037873, rs886037874, rs886037875, rs886037876, rs886037877, rs2490952104, rs1554728327, rs747311061	RCV001332096 RCV000239971 RCV000240276 RCV000240495 RCV000239978 RCV000240257 RCV000240569 RCV003388560 RCV000677203 RCV000677204
Microcephaly	Likely pathogenic	rs2133977803	RCV001728188

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign; Likely benign	rs2273861, rs375225411	RCV005926984 RCV005903014
Cervical cancer	Benign; Uncertain significance	rs2273861, rs144595445	RCV005926986 RCV005926522
Familial pancreatic carcinoma	Benign	rs2273861	RCV005926987
Gastric cancer	Benign	rs2273861	RCV005926990
Hepatocellular carcinoma	Benign	rs2273861, rs73653050	RCV005926985 RCV005904513
IARS1-related disorder	Benign; Likely benign; Uncertain significance	rs556155, rs534075085, rs777991533, rs2230405, rs148687253, rs2230404, rs147625263, rs147022743, rs1830279061, rs188980731, rs751540743, rs370770912, rs2490715050, rs34737051, rs2070053, rs77245714, rs79939916, rs115825549, rs114279476, rs139382751, rs144102700	RCV003976031 RCV003936572 RCV003963683 RCV003973496 RCV003936343 RCV003963380 RCV003403954 RCV003906339 RCV003420716 RCV003901994 RCV003941916 RCV003932264 RCV003976860 RCV003915437 RCV003913280 RCV003962895 RCV003960756 RCV003906046 RCV003906047 RCV003950650 RCV003923177
Lung cancer	Uncertain significance	rs144595445	RCV005926523
Malignant lymphoma, large B-cell, diffuse	Benign	rs2273861	RCV005926988
Malignant tumor of esophagus	Benign	rs73653050	RCV005904514
Sarcoma	Benign	rs2273861	RCV005926989

Associations from Text Mining
Disease Name	Relationship Type	References
Anemia	Associate	29875423
Behcet Syndrome	Associate	27123441
Breast Neoplasms	Associate	17043687, 30229539
Carcinogenesis	Associate	31666286
Carcinoma Hepatocellular	Associate	36550445
Developmental Disabilities	Associate	27891590, 38014478
Diabetic Retinopathy	Associate	39348384
Epilepsy	Associate	38014478
Growth Disorders	Associate	27891590
HEM dysplasia	Associate	30419932
Hypervitaminosis A	Associate	27891590
Hypoalbuminemia	Associate	29875423
Hypokalemia Familial	Associate	29875423
Infant Newborn Diseases	Associate	27891590
Infantile Epileptic Dyskinetic Encephalopathy	Associate	38014478
Insulin Resistance	Associate	11779863
Learning Disabilities	Associate	27891590
Liver Diseases	Associate	27891590
Lung Diseases	Associate	29875423
Neoplasms	Associate	11438664, 32296029
Squamous Cell Carcinoma of Head and Neck	Associate	31315917