LARS1 Gene - Leucyl-tRNA Synthetase 1
Essential enzyme for protein synthesis and mitochondrial function
Gene Information Card
| Symbol | LARS1 |
|---|---|
| Full Name | leucyl-tRNA synthetase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q32 |
| NCBI Gene ID | 51520 ncbi.nlm.nih.gov/gene/51520 |
| Ensembl ID | ENSG00000133706 |
| UniProt ID | Q9P2J5 |
| OMIM ID | 604307 |
| HGNC ID | 6512 |
| Aliases | LARS, LEURS, FLJ20551, KIAA1352 |
Description
The LARS1 gene encodes leucyl-tRNA synthetase 1, a cytoplasmic enzyme that catalyzes the attachment of leucine to its cognate tRNA during protein synthesis. This enzyme belongs to the class I aminoacyl-tRNA synthetase family and is essential for accurate translation. Mutations in LARS1 are associated with autosomal recessive disorders including infantile hepatopathy and Charcot-Marie-Tooth disease type 2.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2 | Loss-of-function mutations impair mitochondrial protein synthesis leading to peripheral neuropathy | ClinVar, OMIM |
| Infantile hepatopathy with lactic acidosis | Defective leucylation disrupts mitochondrial translation causing energy deficiency | OMIM, PubMed |
| Leukodystrophy | Hypomorphic LARS1 variants reduce tRNA charging in oligodendrocytes | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 28.5 | High |
| Heart | 22.3 | High |
| Skeletal muscle | 18.7 | High |
| Brain | 12.1 | Medium |
| Kidney | 15.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 32.1 | Hepatocellular carcinoma cell line |
| K562 | 19.8 | Leukemia cell line |
| HeLa | 24.5 | Cervical adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1565G>A (p.Arg522His) | Missense | Rare | Reduced catalytic activity; associated with Charcot-Marie-Tooth disease |
| c.2000T>C (p.Leu667Pro) | Missense | Rare | Impaired tRNA binding; infantile hepatopathy |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of function; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most reported LARS1 mutations are loss-of-function, reducing leucyl-tRNA synthetase activity and impairing protein synthesis.
Gain of Function (GOF)
No gain-of-function mutations have been described for LARS1.
Dominant Negative (DN)
No dominant-negative mutations have been reported; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • leucine-tRNA ligase activity (GO:0004823) | • translation (GO:0006412) |
| • leucyl-tRNA aminoacylation (GO:0006429) | • cytoplasm (GO:0005737) |
| • mitochondrion (GO:0005739) |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• Cytoplasmic translation (Reactome: R-HSA-72766)
• Mitochondrial translation (Reactome: R-HSA-5389840)
Protein Summary
Leucyl-tRNA synthetase 1 (LARS1) is a 1176-amino acid cytoplasmic enzyme that ligates leucine to the 3' end of tRNA(Leu) in an ATP-dependent reaction. The protein contains an N-terminal catalytic domain, a tRNA-binding domain, and a C-terminal domain involved in dimerization. LARS1 also localizes to mitochondria where it supports organellar translation. Defects in LARS1 cause tissue-specific disorders due to impaired protein synthesis in energy-demanding cells.
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