LARS1 (leucyl-tRNA synthetase 1)

Gene

• Entrez ID: 51520
• Gene name: Leucyl-tRNA synthetase 1
• Gene symbol: LARS1
• Synonyms (NCBI Gene): HSPC192, ILFS1, LARS, LEURS, LEUS, LFIS, LRS, PIG44, RNTLS, cLRS, hr025Cl
• Chromosome: 5
• Chromosome location: 5q32
• Summary: This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase c

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139648263	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs201861847	T>C	Pathogenic	Missense variant, coding sequence variant
rs369437593	G>A,C,T	Likely-pathogenic	Missense variant, coding sequence variant, synonymous variant, stop gained
rs757195926	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs863224047	AAATA>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant
rs863224048	TC>-	Pathogenic	Coding sequence variant, intron variant, frameshift variant, 5 prime UTR variant
rs1057523128	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1057523129	C>G	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IDA	25051973
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004819	Function	Glutamine-tRNA ligase activity	IDA	26869582
GO:0004823	Function	Leucine-tRNA ligase activity	IBA
GO:0004823	Function	Leucine-tRNA ligase activity	IDA	25051973
GO:0004823	Function	Leucine-tRNA ligase activity	IEA
GO:0004823	Function	Leucine-tRNA ligase activity	TAS
GO:0005096	Function	GTPase activator activity	IMP	22424946
GO:0005515	Function	Protein binding	IPI	16055448, 22424946, 28514442, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	22424946
GO:0005737	Component	Cytoplasm	IEA
GO:0005764	Component	Lysosome	IMP	22424946
GO:0005783	Component	Endoplasmic reticulum	IDA	22424946
GO:0005829	Component	Cytosol	IDA	19289464
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:0006425	Process	Glutaminyl-tRNA aminoacylation	IDA	26869582
GO:0006429	Process	Leucyl-tRNA aminoacylation	IBA
GO:0006429	Process	Leucyl-tRNA aminoacylation	IDA	25051973
GO:0006429	Process	Leucyl-tRNA aminoacylation	IEA
GO:0008361	Process	Regulation of cell size	IMP	22424946
GO:0012505	Component	Endomembrane system	IDA	22424946
GO:0016604	Component	Nuclear body	IDA
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:0032008	Process	Positive regulation of TOR signaling	IMP	22424946
GO:0034198	Process	Cellular response to amino acid starvation	IMP	22424946
GO:0043547	Process	Positive regulation of GTPase activity	IMP	22424946
GO:0071230	Process	Cellular response to amino acid stimulus	IMP	22424946
GO:0071233	Process	Cellular response to L-leucine	IMP	22424946
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA
GO:1904263	Process	Positive regulation of TORC1 signaling	IMP	22424946
GO:1990253	Process	Cellular response to leucine starvation	IMP	22424946

Other IDs

• MIM: 151350
• HGNC: 6512
• e!Ensembl: ENSG00000133706

Protein

• UniProt ID: Q9P2J5
• Protein name: Leucine--tRNA ligase, cytoplasmic (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) (cLRS)
• Protein function: Aminoacyl-tRNA synthetase that catalyzes the specific attachment of leucine to its cognate tRNA (tRNA(Leu)) (PubMed:25051973, PubMed:32232361). It performs tRNA aminoacylation in a two-step reaction: Leu is initially activated by ATP to form a l
• PDB: 2WFD, 6KID, 6KIE, 6KQY, 6KR7, 6LPF, 6LR6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	19 → 110	tRNA synthetases class I (I, L, M and V)	Family
  PF00133	tRNA-synt_1	164 → 756	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	794 → 928	Anticodon-binding domain of tRNA ligase	Domain

• Sequence:

  MAERKGTAKVDFLKKIEKEIQQKWDTERVFEVNASNLEKQTSKGKYFVTFPYPYMNGRLH
  LGHTFSLSKCEFAVGYQRLKGKCCLFPFGLHCTGMPIKACADKLKREIELYGCPPDFPDE
  EEEEEETSVKTEDIIIKDKAKGKKSKAAAKAGSSKYQWGIMKSLGLSDEEIVKFSEAEHW
  LDYFPPLAIQDLKRMGLKVDWRRSFITTDVNPYYDSFVRWQFLTLRERNKIKFGKRYTIY
  SPKDGQPCMDHDRQTGEGVGPQEYTLLKLKVLEPYPSKLSGLKGKNIFLVAATLRPETMF
  GQTNCWVRPDMKYIGFETVNGDIFICTQKAARNMSYQGFTKDNGVVPVVKELMGEEILGA
  SLSAPLTSYKVIYVLPMLTIKEDKGTGVVTSVPSDSPDDIAALRDLKKKQALRAKYGIRD
  DMVLPFEPVPVIEIPGFGNLSAVTICDELKIQSQNDREKLAEAKEKIYLKGFYEGIMLVD
  GFKGQKVQDVKKTIQKKMIDAGDALIYMEPEKQVMSRSSDECVVALCDQWYLDYGEENWK
  KQTSQCLKNLETFCEETRRNFEATLGWLQEHACSRTYGLGTHLPWDEQWLIESLSDSTIY
  MAFYTVAHLLQGGNLHGQAESPLGIRPQQMTKEVWDYVFFKEAPFPKTQIAKEKLDQLKQ
  EFEFWYPVDLRVSGKDLVPNHLSYYLYNHVAMWPEQSDKWPTAVRANGHLLLNSEKMSKS
  TGNFLTLTQAIDKFSADGMRLALADAGDTVEDANFVEAMADAGILRLYTWVEWVKEMVAN
  WDSLRSGPASTFNDRVFASELNAGIIKTDQNYEKMMFKEALKTGFFEFQAAKDKYRELAV
  EGMHRELVFRFIEVQTLLLAPFCPHLCEHIWTLLGKPDSIMNASWPVAGPVNEVLIHSSQ
  YLMEVTHDLRLRLKNYMMPAKGKKTDKQPLQKPSHCTIYVAKNYPPWQHTTLSVLRKHFE
  ANNGKLPDNKVIASELGSMPELKKYMKKVMPFVAMIKENLEKMGPRILDLQLEFDEKAVL
  MENIVYLTNSLELEHIEVKFASEAEDKIREDCCPGKPLNVFRIEPGVSVSLVNPQPSNGH
  FSTKIEIRQGDNCDSIIRRLMKMNRGIKDLSKVKLMRFDDPLLGPRRVPVLGKEYTEKTP
  ISEHAVFNVDLMSKKIHLTENGIRVDIGDTIIYLVH

• Sequence length: 1176

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
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Likely pathogenic; Pathogenic	rs2532935153, rs758363727, rs369437593	RCV002302561 RCV002308639 RCV002469057	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Infantile liver failure syndrome 1	Pathogenic; Likely pathogenic	rs770802595, rs369437593, rs1238073820, rs201861847	RCV001353059 RCV001723769 RCV003489384 RCV000055666	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
LARS1-related disorder	Likely pathogenic; Pathogenic	rs369437593	RCV003335191	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENERALIZED SEIZURES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Generalized-onset seizure	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
LIVER FAILURE, INFANTILE, TRANSIENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	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	Likely benign; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROCYTIC NORMOCHROMIC ANEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Normochromic microcytic anemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural hearing loss disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute infantile liver failure-multisystemic involvement syndrome	Liver Failure-Multisystemic Involvement Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Adenomatous Polyposis Coli	Multiple polyposis syndrome	BEFREE	30710880		★☆☆☆☆ Found in Text Mining only
AICARDI-GOUTIERES SYNDROME	Aicardi Goutieres Syndrome	BEFREE	7873876		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	26830138		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia, Macrocytic	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood Coagulation Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Burkitt Lymphoma	Burkitt lymphoma	Pubtator	9525618	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	18446061	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	18446061		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37096225	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	15919814	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	28143555		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	15919814		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Gonadal dysgenesis XX type deafness	Gonadal dysgenesis	Pubtator	23541342, 26657938	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	23541342	Associate	★☆☆☆☆ Found in Text Mining only
INFANTILE LIVER FAILURE SYNDROME 1	Liver failure	GENOMICS_ENGLAND_DG	22607940		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
INFANTILE LIVER FAILURE SYNDROME 1	Liver failure	ORPHANET_DG	22607940		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
INFANTILE LIVER FAILURE SYNDROME 1	Liver failure	UNIPROT_DG	22607940		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
INFANTILE LIVER FAILURE SYNDROME 1	Liver failure	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
INFANTILE LIVER FAILURE SYNDROME 1	Liver failure	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Liver Failure, Acute	Liver failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung Neoplasms	LHGDN	18446061		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	18446061, 37096225	Associate	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	37096225	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	18446061		★☆☆☆☆ Found in Text Mining only
MELAS Syndrome	Melas syndrome	Pubtator	12822890	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neoplasms	Neoplasms	BEFREE	18446061		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	31205503		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	35962451	Associate	★☆☆☆☆ Found in Text Mining only
Rectal Carcinoma	Rectal Carcinoma	BEFREE	29313107		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Synovitis	Synovitis	BEFREE	30406813		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	30710880		★☆☆☆☆ Found in Text Mining only