NARS1: Asparaginyl-tRNA Synthetase 1
A key enzyme in protein synthesis and a potential target in neurological disorders and cancer
Gene Information Card
| Symbol | NARS1 |
|---|---|
| Full Name | asparaginyl-tRNA synthetase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q21.31 |
| NCBI Gene ID | 4677 ncbi.nlm.nih.gov/gene/4677 |
| Ensembl ID | ENSG00000134352 |
| UniProt ID | O43776 |
| OMIM ID | 108410 |
| HGNC ID | 7643 |
| Aliases | NARS, ASNS, NARS1 |
Description
NARS1 encodes the cytoplasmic asparaginyl-tRNA synthetase, an enzyme that catalyzes the attachment of asparagine to its cognate tRNA during protein synthesis. As part of the aminoacyl-tRNA synthetase family, NARS1 is essential for accurate translation. Mutations in NARS1 have been linked to neurodevelopmental disorders and are somatically altered in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities | Loss-of-function mutations impair asparaginyl-tRNA charging, reducing translation fidelity and neuronal protein synthesis | ClinVar, OMIM |
| Colorectal cancer | Somatic missense mutations may alter enzyme activity or substrate specificity, contributing to tumorigenesis | COSMIC |
| Lung adenocarcinoma | Recurrent somatic mutations observed; potential impact on tRNA charging and cell proliferation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Testis | 20.1 | High |
| Pancreas | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression in embryonic kidney cells |
| HeLa | 14.2 | Moderate expression in cervical cancer cells |
| A549 | 11.0 | Moderate expression in lung adenocarcinoma cells |
| HepG2 | 9.5 | Low expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Trp) | Missense | <0.01% | Reduced enzyme activity; associated with neurodevelopmental disorder |
| c.1456G>A (p.Glu486Lys) | Missense | 0.02% | Gain-of-function?; observed in colorectal cancer |
| c.789_790del (p.Glu264fs) | Frameshift | <0.01% | Loss-of-function; likely pathogenic in neurodevelopmental cases |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations reduce or abolish asparaginyl-tRNA charging, impairing protein synthesis.
Gain of Function (GOF)
Some missense variants (e.g., p.Glu486Lys) may increase catalytic activity or alter substrate specificity, potentially driving oncogenesis.
Dominant Negative (DN)
Not clearly established; some missense mutations may interfere with dimerization or complex formation.
View complete mutation data：
Gene Ontology (GO)
| • asparagine-tRNA ligase activity | • ATP binding |
| • tRNA binding | • protein biosynthesis |
| • cytoplasm |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• tRNA charging (Reactome: R-HSA-379716)
Protein Summary
NARS1 is a 548-amino acid cytoplasmic enzyme that forms homodimers and catalyzes the ATP-dependent ligation of asparagine to tRNA-Asn. It belongs to the class II aminoacyl-tRNA synthetase family. The protein contains an N-terminal catalytic domain and a C-terminal anticodon-binding domain. Structural studies show that mutations in the catalytic domain can disrupt substrate binding and reduce enzyme activity.
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