DARS1 Gene (Aspartyl-tRNA Synthetase 1)
A key enzyme in protein synthesis, implicated in Charcot-Marie-Tooth disease and other neurological disorders.
Gene Information Card
| Symbol | DARS1 |
|---|---|
| Full Name | aspartyl-tRNA synthetase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q21.3 |
| NCBI Gene ID | 1615 ncbi.nlm.nih.gov/gene/1615 |
| Ensembl ID | ENSG00000115875 |
| UniProt ID | P14868 |
| OMIM ID | 603084 |
| HGNC ID | 2706 |
| Aliases | AspRS, DARS, HBSL, MGC:117861 |
Description
The DARS1 gene encodes the cytoplasmic aspartyl-tRNA synthetase, an enzyme that catalyzes the attachment of aspartic acid to its cognate tRNA during protein synthesis. It is a member of the class II aminoacyl-tRNA synthetase family. Mutations in DARS1 are associated with Charcot-Marie-Tooth disease type 2O (CMT2O) and hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2O (CMT2O) | Mutations in DARS1 impair aminoacylation activity, leading to peripheral neuropathy. | ClinVar, OMIM |
| Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) | Biallelic mutations cause reduced enzyme function, affecting central nervous system myelination. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Liver | 12.8 | Medium |
| Heart | 10.5 | Medium |
| Skeletal Muscle | 9.1 | Low |
| Kidney | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression |
| HeLa | 14.2 | Medium expression |
| SH-SY5Y | 12.1 | Medium expression |
| HepG2 | 11.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1142G>A (p.Arg381His) | Missense | Rare | Reduced catalytic activity; associated with CMT2O |
| c.1483C>T (p.Arg495Trp) | Missense | Rare | Impaired tRNA binding; associated with HBSL |
| c.1210G>A (p.Glu404Lys) | Missense | Rare | Dominant negative effect; associated with CMT2O |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense mutations (e.g., p.Arg495Trp) reduce enzyme activity, leading to HBSL.
Gain of Function (GOF)
No evidence of gain-of-function mutations in DARS1.
Dominant Negative (DN)
Heterozygous mutations (e.g., p.Arg381His) can exert a dominant-negative effect, causing CMT2O.
View complete mutation data：
Gene Ontology (GO)
| • aspartate-tRNA ligase activity | • ATP binding |
| • tRNA binding | • protein biosynthesis |
| • cytoplasm |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• tRNA Aminoacylation (Reactome: R-HSA-379716)
Protein Summary
The DARS1 protein is a homodimeric enzyme that catalyzes the ATP-dependent ligation of aspartate to tRNA(Asp). It is essential for accurate protein translation. The protein contains an N-terminal anticodon-binding domain and a C-terminal catalytic domain. Mutations affecting these domains disrupt tRNA charging and are linked to neurodegenerative diseases.
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