KARS1: Lysyl-tRNA Synthetase 1
A key enzyme in protein synthesis and mitochondrial function, implicated in Charcot-Marie-Tooth disease and other disorders.
Gene Information Card
| Symbol | KARS1 |
|---|---|
| Full Name | Lysyl-tRNA Synthetase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 3735 ncbi.nlm.nih.gov/gene/3735 |
| Ensembl ID | ENSG00000065427 |
| UniProt ID | Q15046 |
| OMIM ID | 601421 |
| HGNC ID | 6215 |
| Aliases | KARS, KRS, LysRS, DFNB89, CMTRIB |
Description
The KARS1 gene encodes lysyl-tRNA synthetase, an enzyme that catalyzes the attachment of lysine to its cognate tRNA during protein synthesis. This enzyme is a homodimer and belongs to the class II aminoacyl-tRNA synthetase family. KARS1 is essential for both cytoplasmic and mitochondrial translation, as it is imported into mitochondria to charge mitochondrial tRNAs. Mutations in KARS1 are associated with Charcot-Marie-Tooth disease, deafness, and mitochondrial encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease, recessive intermediate B (CMTRIB) | Impaired aminoacylation of mitochondrial and cytoplasmic tRNAs leads to defective protein synthesis in neurons | ClinVar, OMIM |
| Deafness, autosomal recessive 89 (DFNB89) | Reduced lysyl-tRNA charging in cochlear cells disrupts protein synthesis required for hearing | OMIM, ClinVar |
| Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) | Mitochondrial tRNA charging deficiency impairs oxidative phosphorylation | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 18.5 | Medium |
| Kidney | 14.1 | Medium |
| Testis | 20.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.7 | Ubiquitous expression |
| HEK293 | 14.5 | Ubiquitous expression |
| K562 | 12.3 | Ubiquitous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1178G>A (p.Arg393His) | Missense | Rare | Impaired catalytic activity; associated with CMTRIB |
| c.1499C>T (p.Thr500Ile) | Missense | Rare | Reduced tRNA binding; associated with DFNB89 |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of translation initiation; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg393His) reduce aminoacylation activity, leading to protein synthesis defects.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported; KARS1 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • lysine-tRNA ligase activity (GO:0004824) | • mitochondrion (GO:0005739) |
| • cytoplasm (GO:0005737) | • tRNA aminoacylation for protein translation (GO:0006418) |
| • ATP binding (GO:0005524) |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• Mitochondrial translation (Reactome: R-HSA-5389840)
Protein Summary
Lysyl-tRNA synthetase (KARS1) is a 597-amino acid protein that forms a homodimer. It catalyzes the ATP-dependent ligation of lysine to tRNA(Lys). The enzyme has both cytoplasmic and mitochondrial isoforms due to alternative translation start sites. It interacts with the multisynthetase complex (MSC) in the cytoplasm and is imported into mitochondria via its N-terminal mitochondrial targeting sequence. Defects in KARS1 lead to tissue-specific protein synthesis deficiencies, particularly affecting neurons and sensory cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
