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 complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in af... See more...

Aliases for LARS1 Gene

Aliases for LARS1 Gene

  • Leucyl-TRNA Synthetase 1 2 3 5
  • Leucine TRNA Ligase 1, Cytoplasmic 2 3
  • Leucine--TRNA Ligase, Cytoplasmic 3 4
  • Leucyl-TRNA Synthetase 2 4
  • EC 6.1.1.4 4 50
  • HSPC192 2 3
  • RNTLS 2 3
  • LARS 3 4
  • LEUS 2 3
  • Cytoplasmic Leucyl-TRNA Synthetase 3
  • Cytosolic Leucyl-TRNA Synthetase 3
  • Proliferation-Inducing Gene 44 3
  • Leucine Translase 3
  • FLJ10595 2
  • FLJ21788 2
  • KIAA1352 4
  • EC 6.1.1 50
  • Hr025Cl 3
  • ILFS1 3
  • LEURS 3
  • PIG44 3
  • LARS1 5
  • LeuRS 4
  • LFIS 3
  • LRS 3

External Ids for LARS1 Gene

Previous HGNC Symbols for LARS1 Gene

  • LARS

Summaries for LARS1 Gene

Entrez Gene Summary for LARS1 Gene

  • 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 complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]

GeneCards Summary for LARS1 Gene

LARS1 (Leucyl-TRNA Synthetase 1) is a Protein Coding gene. Diseases associated with LARS1 include Infantile Liver Failure Syndrome 1 and Infantile Liver Failure Syndrome. Among its related pathways are Viral mRNA Translation and tRNA Aminoacylation. An important paralog of this gene is VARS2.

UniProtKB/Swiss-Prot Summary for LARS1 Gene

  • Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two 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. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs.

Gene Wiki entry for LARS1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LARS1 Gene

Genomics for LARS1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LARS1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LARS1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LARS1

Genomic Locations for LARS1 Gene

Latest Assembly
chr5:146,110,566-146,182,731
(GRCh38/hg38)
Size:
72,166 bases
Orientation:
Minus strand

Previous Assembly
chr5:145,492,597-145,562,213
(GRCh37/hg19 by Entrez Gene)
Size:
69,617 bases
Orientation:
Minus strand

chr5:145,492,601-145,562,223
(GRCh37/hg19 by Ensembl)
Size:
69,623 bases
Orientation:
Minus strand

Genomic View for LARS1 Gene

Genes around LARS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LARS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LARS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LARS1 Gene

Proteins for LARS1 Gene

  • Protein details for LARS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P2J5-SYLC_HUMAN
    Recommended name:
    Leucine--tRNA ligase, cytoplasmic
    Protein Accession:
    Q9P2J5
    Secondary Accessions:
    • A2RRR4
    • A7E266
    • B4DJ10
    • Q2TU79
    • Q9NSE1

    Protein attributes for LARS1 Gene

    Size:
    1176 amino acids
    Molecular mass:
    134466 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAA92590.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for LARS1 Gene

    Alternative splice isoforms for LARS1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LARS1 Gene

Selected DME Specific Peptides for LARS1 Gene

Q9P2J5:
  • ATLRPET
  • EFEFWYP
  • KGTGVVTSVPSDSPDD
  • PYMNGRLHLGHTFS
  • KFSADGMRL
  • HCTGMPIKACADKLK
  • DECVVALCDQWYL
  • ADAGDTVEDANF
  • KMSKSTGN
  • ALKTGFFE
  • KDGQPCMDHDR
  • SLSDSTIY
  • MVLPFEPVP

Post-translational modifications for LARS1 Gene

  • Ubiquitination at Lys716, Lys719, Lys39, Lys733, Lys45, Lys155, Lys814, Lys193, Lys832, Lys278, Lys341, and Lys659
  • Modification sites at PhosphoSitePlus

Domains & Families for LARS1 Gene

Gene Families for LARS1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for LARS1 Gene

InterPro:
Blocks:
  • Aminoacyl-tRNA synthetase, class Ia
  • Cysteinyl-tRNA synthetase signature

Suggested Antigen Peptide Sequences for LARS1 Gene

GenScript: Design optimal peptide antigens:
  • LARS protein (A2RRR4_HUMAN)
  • cDNA FLJ58157, highly similar to Leucyl-tRNA synthetase, cytoplasmic (EC 6.1.1.4) (B4DER1_HUMAN)
  • cDNA FLJ58533, highly similar to Leucyl-tRNA synthetase, cytoplasmic (EC 6.1.1.4) (B4DJ10_HUMAN)
  • LARS protein (Q0VGM8_HUMAN)
  • LARS protein (Q6NVI4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P2J5

UniProtKB/Swiss-Prot:

SYLC_HUMAN :
  • Belongs to the class-I aminoacyl-tRNA synthetase family.
Family:
  • Belongs to the class-I aminoacyl-tRNA synthetase family.
genes like me logo Genes that share domains with LARS1: view

Function for LARS1 Gene

Molecular function for LARS1 Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two 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. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu); Xref=Rhea:RHEA:11688, Rhea:RHEA-COMP:9613, Rhea:RHEA-COMP:9622, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57427, ChEBI:CHEBI:78442, ChEBI:CHEBI:78494, ChEBI:CHEBI:456215; EC=6.1.1.4;.
UniProtKB/Swiss-Prot EnzymeRegulation:
5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole inhibits LARS1 by forming a covalent adduct with the 3' adenosine of tRNA(Leu) at the editing site, thus locking the enzyme in an inactive conformation.

Enzyme Numbers (IUBMB) for LARS1 Gene

Phenotypes From GWAS Catalog for LARS1 Gene

Gene Ontology (GO) - Molecular Function for LARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0002161 aminoacyl-tRNA editing activity IEA --
GO:0004812 aminoacyl-tRNA ligase activity IEA --
GO:0004819 glutamine-tRNA ligase activity IDA 26869582
GO:0004823 leucine-tRNA ligase activity TAS --
genes like me logo Genes that share ontologies with LARS1: view
genes like me logo Genes that share phenotypes with LARS1: view

Human Phenotype Ontology for LARS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for LARS1 Gene

MGI Knock Outs for LARS1:
  • Lars Lars<tm1b(KOMP)Wtsi>

Animal Models for research

  • Taconic Biosciences Mouse Models for LARS1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LARS1

No data available for Transcription Factor Targets and HOMER Transcription for LARS1 Gene

Localization for LARS1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LARS1 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LARS1 gene
Compartment Confidence
nucleus 5
cytosol 5
endoplasmic reticulum 4
lysosome 4
mitochondrion 2
endosome 2
golgi apparatus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 22424946
GO:0005764 lysosome IMP 22424946
GO:0005783 endoplasmic reticulum IDA 22424946
GO:0005829 cytosol TAS --
GO:0012505 endomembrane system IDA 22424946
genes like me logo Genes that share ontologies with LARS1: view

Pathways & Interactions for LARS1 Gene

genes like me logo Genes that share pathways with LARS1: view

Pathways by source for LARS1 Gene

1 Cell Signaling Technology pathway for LARS1 Gene

Gene Ontology (GO) - Biological Process for LARS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006412 translation IEA --
GO:0006418 tRNA aminoacylation for protein translation TAS --
GO:0006425 glutaminyl-tRNA aminoacylation IDA 26869582
GO:0006429 leucyl-tRNA aminoacylation IBA 21873635
GO:0008361 regulation of cell size IMP 22424946
genes like me logo Genes that share ontologies with LARS1: view

No data available for SIGNOR curated interactions for LARS1 Gene

Drugs & Compounds for LARS1 Gene

(4) Drugs for LARS1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine monophosphate Approved, Investigational Nutra 0
Phosphate Experimental Pharma 0
Leucine Investigational Nutra Target 184
ATP Investigational Nutra 0

(6) Additional Compounds for LARS1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Cer(d18:1/16:0)
  • (2S,3R,4E)-2-Acylamino-1,3-octadec-4-enediol
  • (2S,3R,4E)-2-Acylaminooctadec-4-ene-1,3-diol
  • C16 Cer
  • C16 Ceramide
  • C16-0(Palmitoyl)ceramide
24696-26-2
pyrophosphate
  • [(HO)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • Pyrophosphoric acid
14000-31-8
genes like me logo Genes that share compounds with LARS1: view

Transcripts for LARS1 Gene

mRNA/cDNA for LARS1 Gene

4 REFSEQ mRNAs :
30 NCBI additional mRNA sequence :
32 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LARS1

Alternative Splicing Database (ASD) splice patterns (SP) for LARS1 Gene

No ASD Table

Relevant External Links for LARS1 Gene

GeneLoc Exon Structure for
LARS1

Expression for LARS1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LARS1

SOURCE GeneReport for Unigene cluster for LARS1 Gene:

Hs.432674

Evidence on tissue expression from TISSUES for LARS1 Gene

  • Nervous system(5)
  • Liver(4.7)
  • Heart(3.1)
  • Skin(3)
  • Intestine(2.9)
  • Muscle(2.7)
  • Pancreas(2.5)
  • Kidney(2.4)
  • Blood(2.3)
  • Eye(2.3)
  • Lung(2.3)
  • Spleen(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LARS1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • head
  • skull
Abdomen:
  • liver
General:
  • blood
  • coagulation system
  • red blood cell
genes like me logo Genes that share expression patterns with LARS1: view

Primer products for research

No data available for mRNA expression in normal human tissues , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for LARS1 Gene

Orthologs for LARS1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for LARS1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LARS 29 30
  • 99.35 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LARS 29 30
  • 92.38 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LARS 29 30
  • 91.01 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Lars 29
  • 86.9 (n)
Mouse
(Mus musculus)
Mammalia Lars 29 16 30
  • 85.97 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia LARS 30
  • 85 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia LARS 30
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LARS 29 30
  • 79.11 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LARS 30
  • 85 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lars 29
  • 75.88 (n)
Str.5585 29
Zebrafish
(Danio rerio)
Actinopterygii larsa 30 30
  • 79 (a)
OneToMany
larsb 29 30
  • 71.02 (n)
OneToMany
wufb36b12 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG33123 29 30
  • 59.98 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008297 29
  • 58.48 (n)
Worm
(Caenorhabditis elegans)
Secernentea lars-1 29 30
  • 59.57 (n)
OneToOne
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AAL088W 29
  • 54.2 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D06105g 29
  • 53.83 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CDC60 29 30 32
  • 53.43 (n)
OneToOne
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT1G09620 29
  • 56.22 (n)
Soybean
(Glycine max)
eudicotyledons Gma.978 29
Rice
(Oryza sativa)
Liliopsida Os09g0503400 29
  • 57.78 (n)
Os.24539 29
Barley
(Hordeum vulgare)
Liliopsida Hv.6307 29
Wheat
(Triticum aestivum)
Liliopsida Ta.7517 29
Corn
(Zea mays)
Liliopsida Zm.12595 29
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9718 30
  • 63 (a)
OneToOne
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes lrs1 29
  • 56.88 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU09463 29
  • 51.34 (n)
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.11019 29
Species where no ortholog for LARS1 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for LARS1 Gene

ENSEMBL:
Gene Tree for LARS1 (if available)
TreeFam:
Gene Tree for LARS1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LARS1: view image
Alliance of Genome Resources:
Additional Orthologs for LARS1

Paralogs for LARS1 Gene

Paralogs for LARS1 Gene

genes like me logo Genes that share paralogs with LARS1: view

Variants for LARS1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LARS1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
1028641 Uncertain Significance: Infantile liver failure syndrome 1 146,149,686(-) T/C
NM_020117.11(LARS1):c.1439A>G (p.Asp480Gly)
MISSENSE
1029737 Uncertain Significance: Infantile liver failure syndrome 1 146,172,715(-) C/T
NM_020117.11(LARS1):c.185G>A (p.Gly62Glu)
MISSENSE
1029738 Uncertain Significance: Infantile liver failure syndrome 1 146,157,498(-) A/C
NM_020117.11(LARS1):c.970T>G (p.Phe324Val)
MISSENSE
1033930 Pathogenic: Infantile liver failure syndrome 1 146,143,476(-) TG/T
NM_020117.11(LARS1):c.1812del (p.Phe603_Tyr604insTer)
NONSENSE
1048520 Pathogenic: Infantile liver failure syndrome 1 146,130,142(-) T/C
NM_020117.11(LARS1):c.2504A>G (p.Tyr835Cys)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LARS1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for LARS1 Gene

Variant ID Type Subtype PubMed ID
esv1264154 CNV insertion 17803354
nsv1137533 CNV deletion 24896259
nsv1153535 CNV duplication 26484159
nsv428128 CNV loss 18775914
nsv969002 CNV duplication 23825009

Variation tolerance for LARS1 Gene

Residual Variation Intolerance Score: 24.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.85; 93.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LARS1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
LARS1
Leiden Open Variation Database (LOVD)
LARS1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LARS1 Gene

Disorders for LARS1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for LARS1 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
infantile liver failure syndrome 1
  • ilfs1
infantile liver failure syndrome
  • infantile liver failure
supine hypotensive syndrome
  • antepartum maternal hypotension syndrome
microcytic anemia
  • iron-refractory iron deficiency anemia
robinow syndrome, autosomal recessive 1
  • rrs1
- elite association - COSMIC cancer census association via MalaCards
Search LARS1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SYLC_HUMAN
  • Infantile liver failure syndrome 1 (ILFS1) [MIM:615438]: A life-threatening disorder of hepatic function that manifests with acute liver failure in the first few months of life. Clinical features include anemia, renal tubulopathy, developmental delay, seizures, failure to thrive, and liver steatosis and fibrosis. {ECO:0000269 PubMed:22607940}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for LARS1

genes like me logo Genes that share disorders with LARS1: view

No data available for Genatlas for LARS1 Gene

Publications for LARS1 Gene

  1. Identification of a mutation in LARS as a novel cause of infantile hepatopathy. (PMID: 22607940) Casey JP … Ennis S (Molecular genetics and metabolism 2012) 3 4 72
  2. Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles. (PMID: 19426743) Seiradake E … Cusack S (Journal of molecular biology 2009) 3 4 22
  3. A paradigm shift for the amino acid editing mechanism of human cytoplasmic leucyl-tRNA synthetase. (PMID: 19702327) Pang YL … Martinis SA (Biochemistry 2009) 3 22
  4. Implication of leucyl-tRNA synthetase 1 (LARS1) over-expression in growth and migration of lung cancer cells detected by siRNA targeted knock-down analysis. (PMID: 18446061) Shin SH … Chung YJ (Experimental & molecular medicine 2008) 3 22
  5. A single residue in leucyl-tRNA synthetase affecting amino acid specificity and tRNA aminoacylation. (PMID: 17378584) Lue SW … Kelley SO (Biochemistry 2007) 3 22

Products for LARS1 Gene

Sources for LARS1 Gene