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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	Likely pathogenic; Pathogenic	rs2532935153, rs758363727, rs369437593	RCV002302561 RCV002308639 RCV002469057
Infantile liver failure syndrome 1	Pathogenic; Likely pathogenic	rs770802595, rs369437593, rs1238073820, rs201861847	RCV001353059 RCV001723769 RCV003489384 RCV000055666
LARS1-related disorder	Likely pathogenic; Pathogenic	rs369437593	RCV003335191

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Likely benign; Benign	rs199826165, rs17104268, rs67107752	RCV005911503 RCV005890901 RCV005868077
Cervical cancer	Benign; Likely benign	rs73315769, rs141790396	RCV005918868 RCV005893506
Cholangiocarcinoma	Likely benign; Benign	rs199826165, rs67107752	RCV005911506 RCV005868078
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	rs17104268	RCV005890910
Familial cancer of breast	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	rs199826165, rs373591577, rs139456270, rs3763373, rs17104268, rs141790396, rs373663096	RCV005911502 RCV005916272 RCV005922782 RCV005890899 RCV005890900 RCV005893504 RCV005898841
Familial pancreatic carcinoma	Benign	rs17104268	RCV005890905
Gastric cancer	Conflicting classifications of pathogenicity	rs139456270	RCV005922783
Generalized-onset seizure	Uncertain significance	rs759215928	RCV001250473
Global developmental delay	Uncertain significance	rs759215928	RCV001250473
Lung cancer	Likely benign	rs199826165	RCV005911507
Lymphoma	Benign	rs17104268	RCV005890906
Malignant lymphoma, large B-cell, diffuse	Benign	rs61732382	RCV005890911
Malignant tumor of esophagus	Likely benign; Uncertain significance; Benign	rs199826165, rs373591577, rs141790396	RCV005911504 RCV005916273 RCV005893505
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	rs762913390	RCV005893503
Microcephaly	Likely benign	rs200109165	RCV001252834
Nonpapillary renal cell carcinoma	Benign	rs17104268	RCV005890902
Normochromic microcytic anemia	Uncertain significance	rs759215928	RCV001250473
Ovarian cancer	Likely benign; Benign	rs199826165, rs17104268	RCV005911505 RCV005890903
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity; Benign; Likely benign	rs139456270, rs141790396	RCV005922784 RCV005893508
Sarcoma	Benign; Likely benign	rs73315769, rs141790396, rs181291967	RCV005918869 RCV005893507 RCV005900837
Sensorineural hearing loss disorder	Uncertain significance	rs759215928	RCV001250473
Thymoma	Benign	rs17104268	RCV005890908
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	rs141790396	RCV005893509
Uterine carcinosarcoma	Benign	rs17104268	RCV005890907
Uterine corpus endometrial carcinoma	Benign	rs73315769, rs17104268, rs67107752	RCV005918870 RCV005890909 RCV005868079
Uveal melanoma	Benign	rs17104268	RCV005890904

Associations from Text Mining
Disease Name	Relationship Type	References
Anemia	Associate	29875423
Burkitt Lymphoma	Associate	9525618
Carcinogenesis	Associate	18446061
Colorectal Neoplasms	Associate	37096225
Diabetes Mellitus Type 2	Associate	15919814
Gonadal dysgenesis XX type deafness	Associate	23541342, 26657938
Hearing Loss	Associate	23541342
Hypoalbuminemia	Associate	29875423
Hypokalemia Familial	Associate	29875423
Lung Diseases	Associate	29875423
Lung Neoplasms	Associate	18446061, 37096225
Lymphatic Metastasis	Associate	37096225
MELAS Syndrome	Associate	12822890
Noninsulin dependent diabetes mellitus with deafness	Associate	12822890
Osteosarcoma	Associate	35962451
Primary Ovarian Insufficiency	Associate	23541342