QARS1

Chr 3AR

glutaminyl-tRNA synthetase 1

Also known as: GLNRS, MSCCA, PRO2195, QARS

NCBI Gene: 5859ENSG00000172053UniProt: P47897

Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. In metazoans, 9 aminoacyl-tRNA synthetases specific for glutamine (gln), glutamic acid (glu), and 7 other amino acids are associated within a multienzyme complex. Although present in eukaryotes, glutaminyl-tRNA synthetase (QARS) is absent from many prokaryotes, mitochondria, and chloroplasts, in which Gln-tRNA(Gln) is formed by transamidation of the misacylated Glu-tRNA(Gln). Glutaminyl-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

Microcephaly, progressive, seizures, and cerebral and cerebellar atrophyMIM #615760
AR
0
Active trials
29
Pathogenic / LP
473
ClinVar variants
7
Pubs (1 yr)
0.2
Missense Z
0.81
LOEUF
Clinical Summary— QARS1
🧬
Gene-Disease Validity (ClinGen)
diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 146 VUS of 473 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.64
OE 0.59 (0.43–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.97 (0.90–1.05)
438 obs / 451.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.43–0.81)
0≤0.351.4
Missense OE0.97 (0.90–1.05)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 28 / 47.6Missense obs/exp: 438 / 451.2Syn Z: -1.03
DN
DN
0.6259th %ile
GOF
0.5464th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

473 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic10
VUS146
Likely Benign294
Benign4
19
Pathogenic
10
Likely Pathogenic
146
VUS
294
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
9
0
19
Likely Pathogenic
8
0
2
0
10
VUS
0
128
17
1
146
Likely Benign
0
4
176
114
294
Benign
0
0
4
0
4
Total17133208115473

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

QARS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

QARS1-related microcephaly, progressive, seizures, and cerebral and cerebellar atrophy

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
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.
Ahmad R et al.·Mol Biol Rep
2025Review
[QARS1 gene related glutaminyl-tRNA synthetase deficiency syndrome: report of three cases and a review of literature].
Shen YW et al.·Zhonghua Er Ke Za Zhi
2020Review
A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders.
Chan DL et al.·Brain Dev
2022Case report
Childhood-onset focal epilepsy and acute para-infectious encephalopathy in a patient with biallelic QARS1 variants.
Yahya V et al.·Neurol Sci
2025Case report
Previously defined variants of uncertain significance may play an important role in epilepsy and interactions between certain variants may become pathogenic.
Hussein Y et al.·Epilepsia Open
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients