QARS1

Chr 3AR

glutaminyl-tRNA synthetase 1

Also known as: GLNRS, MSCCA, PRO2195, QARS

NCBI Gene: 5859ENSG00000172053UniProt: P47897OMIM: 603727

Glutaminyl-tRNA synthetase catalyzes the attachment of glutamine to its cognate tRNA molecules, playing a critical role in brain development. Biallelic mutations cause autosomal recessive microcephaly with progressive seizures and cerebral and cerebellar atrophy. The gene shows minimal constraint against loss-of-function variants (very low pLI), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.811 OMIM phenotype
Clinical Summary— QARS1
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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.
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ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 59 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongQARS1-related microcephaly, progressive, seizures, and cerebral and cerebellar atrophyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6259th %ile
GOF
0.5464th %ile
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic6
VUS59
Likely Benign123
Benign1
11
Pathogenic
6
Likely Pathogenic
59
VUS
123
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
2
0
11
Likely Pathogenic
5
0
1
0
6
VUS
0
51
8
0
59
Likely Benign
0
4
71
48
123
Benign
0
0
1
0
1
Total14558348200

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

View in ClinVar →

Protein Context — Lollipop Plot

QARS1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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
2025Open AccessReview
Homozygous Mutation in the QARS1 Gene Causing Developmental Epileptic Encephalopathy in Siblings in the Southeast Asian Region: An Interesting Case Report and Discussion.
Srivastava P et al.·Cureus
2025Open AccessCase report
Third trimester diagnosis of a compound heterozygous QARS1 mutation based upon microcephaly and abnormal placenta.
Hackelöer M et al.·Case Rep Perinat Med
2025Open Access
Childhood-onset focal epilepsy and acute para-infectious encephalopathy in a patient with biallelic QARS1 variants.
Yahya V et al.·Neurol Sci
2025
A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders.
Chan DL et al.·Brain Dev
2022Review
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