WARS1: Tryptophanyl-tRNA Synthetase 1
A key enzyme in protein synthesis with roles in angiogenesis and immune regulation
Gene Information Card
| Symbol | WARS1 |
|---|---|
| Full Name | Tryptophanyl-tRNA Synthetase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 7453 ncbi.nlm.nih.gov/gene/7453 |
| Ensembl ID | ENSG00000140105 |
| UniProt ID | P23381 |
| OMIM ID | 191050 |
| HGNC ID | 12729 |
| Aliases | WARS, IFI53, GAMMA-2, HMNJ, TrpRS |
Description
WARS1 encodes tryptophanyl-tRNA synthetase, a class I aminoacyl-tRNA synthetase that catalyzes the attachment of tryptophan to its cognate tRNA. The enzyme is essential for protein synthesis and also has non-canonical functions in angiogenesis, inflammation, and immune response. Alternative splicing generates multiple isoforms, including a truncated form with angiostatic properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease, axonal, type 2J | Loss-of-function mutations impair tRNA charging, leading to peripheral neuropathy | OMIM #606461 |
| Hereditary motor and sensory neuropathy, type VI | Dominant-negative mutations disrupt dimerization and catalytic activity | OMIM #614489 |
| Distal hereditary motor neuropathy, type J | Missense mutations cause progressive motor neuron degeneration | OMIM #608627 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 45.2 | High |
| Salivary gland | 38.1 | High |
| Liver | 32.7 | High |
| Kidney | 28.5 | High |
| Lung | 22.3 | Medium |
| Brain | 15.6 | Medium |
| Heart | 12.4 | Medium |
| Skeletal muscle | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 35.1 | Cervical adenocarcinoma |
| HepG2 | 42.3 | Hepatocellular carcinoma |
| A549 | 28.7 | Lung carcinoma |
| K562 | 19.4 | Chronic myeloid leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.833G>A (p.Arg278His) | Missense | Rare | Impaired catalytic activity; associated with CMT2J |
| c.1249C>T (p.Arg417Cys) | Missense | Rare | Dominant-negative effect; causes HMNJ |
| c.1463G>A (p.Arg488Gln) | Missense | Rare | Reduced tRNA charging; linked to neuropathy |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous loss-of-function mutations are not viable; heterozygous missense mutations reduce catalytic efficiency.
Gain of Function (GOF)
Not reported for WARS1.
Dominant Negative (DN)
Mutations such as p.Arg417Cys disrupt dimerization and inhibit wild-type enzyme activity, leading to dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • tryptophan-tRNA ligase activity (GO:0004812) | • ATP binding (GO:0005524) |
| • tryptophanyl-tRNA aminoacylation (GO:0006436) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • aminoacyl-tRNA synthetase multienzyme complex (GO:0017101) |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• Cytoplasmic tRNA aminoacylation (Reactome: R-HSA-379716)
Protein Summary
Tryptophanyl-tRNA synthetase 1 (TrpRS) is a 471-amino acid protein that forms a homodimer. It catalyzes the ATP-dependent attachment of tryptophan to tRNA(Trp). The full-length enzyme (T1-TrpRS) is involved in protein synthesis, while an alternative splice variant (T2-TrpRS) lacks the N-terminal domain and exhibits anti-angiogenic activity. The protein is also secreted under inflammatory conditions and modulates immune responses.
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