QARS1: Glutaminyl-tRNA Synthetase 1
A critical enzyme for protein translation and mitochondrial function, associated with neurodegenerative disorders.
Gene Information Card
| Symbol | QARS1 |
|---|---|
| Full Name | Glutaminyl-tRNA Synthetase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 5859 ncbi.nlm.nih.gov/gene/5859 |
| Ensembl ID | ENSG00000172053 |
| UniProt ID | P47897 |
| OMIM ID | 603727 |
| HGNC ID | 9751 |
| Aliases | QARS, GLNRS, PRO2195 |
Description
The QARS1 gene encodes glutaminyl-tRNA synthetase, a class I aminoacyl-tRNA synthetase that catalyzes the attachment of glutamine to its cognate tRNA during protein synthesis. The enzyme is essential for both cytoplasmic and mitochondrial translation. Mutations in QARS1 cause progressive microcephaly, seizures, and cerebral atrophy, often with mitochondrial dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive microcephaly with seizures and cerebral atrophy | Loss-of-function mutations impair tRNA charging, leading to defective protein synthesis and mitochondrial dysfunction | ClinVar, OMIM |
| Mitochondrial respiratory chain deficiency | Reduced QARS1 activity disrupts mitochondrial translation, causing complex I and IV deficiencies | PubMed, OMIM |
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Biallelic missense variants affect enzyme stability and catalytic efficiency | ClinVar, HGNC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 10.5 | Medium |
| Kidney | 11.3 | Medium |
| Testis | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.1 | High expression |
| HeLa | 12.5 | Moderate expression |
| SH-SY5Y | 13.0 | Neuronal model, relevant for disease studies |
| HepG2 | 11.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.43G>A (p.Gly15Arg) | Missense | Rare | Reduced catalytic activity; associated with microcephaly |
| c.1286G>A (p.Arg429His) | Missense | Rare | Impaired tRNA binding; reported in epilepsy |
| c.1690C>T (p.Arg564Trp) | Missense | Rare | Loss of function; compound heterozygotes cause severe phenotype |
| c.2023C>T (p.Arg675*) | Nonsense | Rare | Premature truncation; loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most QARS1 mutations are loss-of-function, reducing tRNA charging efficiency and impairing protein synthesis, especially in mitochondria.
Gain of Function (GOF)
No gain-of-function mutations have been reported for QARS1.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with dimerization or complex formation, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • glutamine-tRNA ligase activity | • ATP binding |
| • tRNA binding | • protein biosynthesis |
| • mitochondrial translation | • cytoplasmic translation |
Pathways
• Aminoacyl-tRNA biosynthesis (KEGG: hsa00970)
• Mitochondrial translation (Reactome: R-HSA-5389840)
• Cytoplasmic translation (Reactome: R-HSA-72766)
Protein Summary
QARS1 encodes a 775-amino acid protein that functions as a homodimer. It contains a catalytic domain, an anticodon-binding domain, and a mitochondrial targeting sequence. The enzyme is essential for accurate protein synthesis in both the cytoplasm and mitochondria. Defects in QARS1 lead to impaired mitochondrial translation, resulting in respiratory chain deficiencies and severe neurological phenotypes.
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