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

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
Global developmental delay	Likely pathogenic	rs2133977803	RCV001728188	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microcephaly	Likely pathogenic	rs2133977803	RCV001728188	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Uncertain significance	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
GROWTH RETARDATION, IMPAIRED INTELLECTUAL DEVELOPMENT, HYPOTONIA, AND HEPATOPATHY	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IARS1-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Uncertain significance	ClinVar	★★☆☆☆ 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
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Antisocial Personality Disorder	Antisocial Personality Disorder	BEFREE	29778051		★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Abdominal	Aortic Aneurysm	BEFREE	30905780		★☆☆☆☆ Found in Text Mining only
Behcet Syndrome	Behcet disease	Pubtator	27123441	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	15509777, 17361103, 17956604, 23562473, 29685905, 30229539		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	17043687, 30229539	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	31666286	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	17956604		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	36550445	Associate	★☆☆☆☆ Found in Text Mining only
Clear-cell metastatic renal cell carcinoma	Renal Carcinoma	BEFREE	17443497		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	29185229		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	19201454		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	27891590, 38014478	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	22869320, 28065675, 31404179, 9726601		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	22869320, 28065675, 31404179, 9726601		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	11256583, 11641236, 12213887, 16603055, 30773997, 31404179		★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	39348384	Associate	★☆☆☆☆ Found in Text Mining only
Embryonal Rhabdomyosarcoma	Embryonal Rhabdomyosarcoma	BEFREE	8410116		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	38014478	Associate	★☆☆☆☆ Found in Text Mining only
Fibroadenoma	Fibroadenoma	BEFREE	17956604		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	26892260		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	26892260		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Graves Disease	Graves Disease	BEFREE	30504400		★☆☆☆☆ Found in Text Mining only
Growth delay-intellectual disability-hepatopathy syndrome	Growth Delay-Intellectual Disability-Hepatopathy Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	27891590	Associate	★☆☆☆☆ Found in Text Mining only
GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY	Growth Retardation, Intellectual Developmental Disorder, Hypotonia, And Hepatopathy	GENOMICS_ENGLAND_DG	27426735, 29903433		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY	Growth Retardation, Intellectual Developmental Disorder, Hypotonia, And Hepatopathy	ORPHANET_DG	27426735, 29052218		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY	Growth Retardation, Intellectual Developmental Disorder, Hypotonia, And Hepatopathy	UNIPROT_DG	27426735		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY	Growth Retardation, Intellectual Developmental Disorder, Hypotonia, And Hepatopathy	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY	Growth Retardation, Intellectual Developmental Disorder, Hypotonia, And Hepatopathy	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hematologic Neoplasms	Hematologic Neoplasms	BEFREE	30328953		★☆☆☆☆ Found in Text Mining only
Hematological Disease	Hematological Disease	BEFREE	30328953		★☆☆☆☆ Found in Text Mining only
Hydronephrosis	Hydronephrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperandrogenism	Hyperandrogenism	BEFREE	29719598		★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	30285704		★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	BEFREE	23483710		★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	21945886		★☆☆☆☆ Found in Text Mining only
Hypertrophic obstructive cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	21945886		★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	11779863	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial Aneurysm	BEFREE	30233292		★☆☆☆☆ Found in Text Mining only
Learning Disabilities	Learning disorders	Pubtator	27891590	Associate	★☆☆☆☆ Found in Text Mining only
Lipid Metabolism Disorders	Lipid Metabolism Disorders	BEFREE	31468392		★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	27891590	Associate	★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	15509777, 17361103, 23562473, 29685905, 30229539		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	14604996		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	21387109, 25267499		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19920186, 20648017, 23562473, 28234626		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	22869320		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	GENOMICS_ENGLAND_DG	27426735		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neoplasms	Neoplasms	BEFREE	11526511, 23053896, 26758558, 28600491, 29533008, 30064461, 30675236, 30883338, 8410116		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	27207326		★☆☆☆☆ Found in Text Mining only
Nodular Goiter	Nodular Goiter	BEFREE	30504400		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	27825546, 28600491		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	8620344		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	14604996		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic Ovary Syndrome	BEFREE	15665022, 16603055, 22523112		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	19055661		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	21387109, 25267499		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	BEFREE	31062065		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	29778051		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31315917	Associate	★☆☆☆☆ Found in Text Mining only