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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
QARS1
glutaminyl-tRNA synthetase 1
Chromosome 3 Β· 3p21.31
NCBI Gene: 5859Ensembl: ENSG00000172053.19HGNC: HGNC:9751UniProt: B7Z840
202PubMed Papers
21Diseases
0Drugs
69Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of apoptotic signaling pathwaycytoplasmnegative regulation of DNA-templated transcriptioncytosolDiffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndromediffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndromegenetic disorderintellectual disability, autosomal dominant 43
✦AI Summary

QARS1 encodes glutaminyl-tRNA synthetase 1, which catalyzes the aminoacylation of tRNA with glutamine, a critical step in protein translation 1. QARS1 plays a crucial role in brain development 2 and functions as a component of the human multi-tRNA synthetase complex, where it associates with arginyl-tRNA synthetase 1 and ARS-interacting multifunctional proteins through leucine zipper motifs 3. Beyond canonical translation, QARS1 interacts with antiviral proteins and transcriptional regulators in response to interferon signaling 4. Pathogenic QARS1 variants cause progressive microcephaly with seizures and cerebral/cerebellar atrophy (MSCCA), characterized by a clinical pentad of microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation, and severe muscle hypotonia 56. Most reported patients exhibit severe, drug-resistant neonatal-onset seizures 6; however, milder phenotypes with later-onset focal seizures or nonepileptic presentations have been documented, associated with preserved tRNA aminoacylation activity or reduced protein solubility 678. Additionally, QARS1 may influence breast cancer cell proliferation through amino acid metabolism 9. Early genetic diagnosis is essential for QARS1-related encephalopathy to enable personalized treatment strategies and genetic counseling 8.

Sources cited
1
QARS1 encodes glutamine-tRNA ligase (glutaminyl-tRNA synthetase)
PMID: 26869582
2
QARS1 plays a critical role in brain development
PMID: 24656866
3
QARS1 is a component of the human multi-tRNA synthetase complex interacting with RARS1, AIMP1, and AIMP2 through leucine zipper motifs
PMID: 39542129
4
QARS1 interacts with antiviral proteins (IFIT1, IFIT3) and transcriptional regulators in cytoplasm during interferon response
PMID: 40894660
5
QARS1 mutations cause progressive microcephaly with seizures and cerebral atrophy characterized by severe global developmental retardation, intractable early-onset epileptic encephalopathy, and severe muscle hypotonia
PMID: 33256324
6
QARS1 variants associated with epilepsy, developmental regression, progressive microcephaly, and cerebral atrophy; most patients have drug-resistant epilepsy
PMID: 34774383
7
Homozygous missense QARS1 variants may lead to milder phenotypes with nonepileptic presentation and severe intellectual disability
PMID: 40448856
8
Milder QARS1-related encephalopathies present with childhood-onset focal seizures, developmental delay, and short stature; early genetic diagnosis enables personalized treatment
PMID: 39715963
9
QARS1 may influence breast cancer cell proliferation through methionine metabolism
PMID: 40493339
Disease Associationsβ“˜21
Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndromeOpen Targets
0.79Strong
diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndromeOpen Targets
0.73Strong
genetic disorderOpen Targets
0.42Moderate
intellectual disability, autosomal dominant 43Open Targets
0.34Weak
microcephalyOpen Targets
0.30Weak
Abnormality of the skeletal systemOpen Targets
0.15Weak
attention deficit hyperactivity disorderOpen Targets
0.12Weak
hypertensionOpen Targets
0.11Weak
glaucomaOpen Targets
0.06Suggestive
smoking cessationOpen Targets
0.04Suggestive
nicotine dependenceOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.04Suggestive
Isolated anophthalmia - microphthalmiaOpen Targets
0.04Suggestive
microphthalmiaOpen Targets
0.04Suggestive
microphthalmia, isolated, with coloboma 10Open Targets
0.04Suggestive
X-linked retinoschisisOpen Targets
0.03Suggestive
exudative vitreoretinopathy 2, X-linkedOpen Targets
0.03Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.03Suggestive
microphthalmia, isolated, with coloboma 5Open Targets
0.03Suggestive
X-linked retinal dysplasiaOpen Targets
0.03Suggestive
Microcephaly, progressive, with seizures and cerebral and cerebellar atrophyUniProt
Pathogenic Variants69
NM_005051.3(QARS1):c.1543C>T (p.Arg515Trp)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome|not provided|Intellectual disability, autosomal dominant 43
β˜…β˜…β˜†β˜†2026β†’ Residue 515
NM_005051.3(QARS1):c.1758+1G>TLikely pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2025
NM_005051.3(QARS1):c.477G>A (p.Trp159Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 159
NM_005051.3(QARS1):c.1362_1365del (p.Leu455fs)Pathogenic
not provided|Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 455
NM_005051.3(QARS1):c.1272_1279del (p.His426fs)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 426
NM_005051.3(QARS1):c.134G>T (p.Gly45Val)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome|not provided|QARS1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 45
NM_005051.3(QARS1):c.1451del (p.Tyr484fs)Pathogenic
not provided|Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 484
NM_005051.3(QARS1):c.1009_1012del (p.Asp337fs)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 337
NM_005051.3(QARS1):c.1387C>T (p.Arg463Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 463
NM_005051.3(QARS1):c.1164+1G>CLikely pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome|not provided
β˜…β˜…β˜†β˜†2024
NM_005051.3(QARS1):c.1567C>T (p.Arg523Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 523
NM_005051.3(QARS1):c.1758+1G>CLikely pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025
NM_005051.3(QARS1):c.1930dup (p.Val644fs)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 644
NM_005051.3(QARS1):c.14_35del (p.Asp5fs)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 5
NM_005051.3(QARS1):c.1657dup (p.Leu553fs)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 553
NM_005051.3(QARS1):c.585del (p.Arg195_Leu196insTer)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 195
NM_005051.3(QARS1):c.1896G>A (p.Trp632Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 632
NM_005051.3(QARS1):c.972G>A (p.Trp324Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 324
NM_005051.3(QARS1):c.1345G>T (p.Glu449Ter)Pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 449
NM_005051.3(QARS1):c.2084+1G>ALikely pathogenic
Diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome
β˜…β˜†β˜†β˜†2024
View on ClinVar β†—
Related Genes
AARS1Protein interaction100%CARS1Protein interaction100%DARS1Protein interaction100%GARS1Protein interaction100%IARS1Protein interaction100%KARS1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
98%
Ovary
91%
Lung
85%
Liver
70%
Brain
33%
Gene Interaction Network
Click a node to explore
QARS1AARS1CARS1DARS1GARS1IARS1KARS1
PROTEIN STRUCTURE
Preparing viewer…
PDB4YE6 Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.59–0.85]
RankingsWhere QARS1 stands among ~20K protein-coding genes
  • #2,086of 20,598
    Most Researched202 Β· top quartile
  • #1,050of 5,498
    Most Pathogenic Variants69 Β· top quartile
  • #7,434of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedQARS1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Assembly of the Human Multi-tRNA Synthetase Complex Through Leucine Zipper Motifs.
PMID: 39542129
J Mol Biol Β· 2024
1.00
2
[QARS1 gene related glutaminyl-tRNA synthetase deficiency syndrome: report of three cases and a review of literature].
PMID: 33256324
Zhonghua Er Ke Za Zhi Β· 2020
0.90
3
Molecular biomarkers for the prognosis of breast cancer: role of amino acid metabolism genes.
PMID: 40493339
J Physiol Biochem Β· 2025
0.80
4
A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders.
PMID: 34774383
Brain Dev Β· 2022
0.70
5
QARS1 associated developmental epileptic encephalopathy: first report of a rare homozygous missense variant from Pakistan causing nonepileptic phenotype in a family of seven patients and a comprehensive review of the literature.
PMID: 40448856
Mol Biol Rep Β· 2025
0.60