QRSL1

Chr 6AR

glutaminyl-tRNA amidotransferase subunit QRSL1

Also known as: COXPD40, GatA

NCBI Gene: 55278ENSG00000130348UniProt: Q9H0R6

Contributes to glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 40. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 40MIM #618835
AR
204
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— QRSL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 88 VUS of 204 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.89LOEUF
pLI 0.000
Z-score 1.99
OE 0.59 (0.40–0.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.07Z-score
OE missense 0.82 (0.73–0.91)
228 obs / 278.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.40–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.73–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 16 / 27.2Missense obs/exp: 228 / 278.4Syn Z: -0.59

ClinVar Variant Classifications

204 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic5
VUS88
Likely Benign50
Benign32
Conflicting5
24
Pathogenic
5
Likely Pathogenic
88
VUS
50
Likely Benign
32
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
19
0
24
Likely Pathogenic
3
1
1
0
5
VUS
1
73
13
1
88
Likely Benign
0
5
12
33
50
Benign
0
4
22
6
32
Conflicting
—5
Total7856740204

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

View in ClinVar →

Protein Context — Lollipop Plot

QRSL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 40

MIM #618835

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.
Kohda M et al.·PLoS Genet
2016
Genetic defects in mtDNA-encoded protein translation cause pediatric, mitochondrial cardiomyopathy with early-onset brain disease.
Kamps R et al.·Eur J Hum Genet
2018Case report
Germline Exome Sequencing for Men with Testicular Germ Cell Tumor Reveals Coding Defects in Chromosomal Segregation and Protein-targeting Genes.
Pyle LC et al.·Eur Urol
2024
Recent topics: the diagnosis, molecular genesis, and treatment of mitochondrial diseases.
Murayama K et al.·J Hum Genet
2019Review
Muscle fat replacement and modified ragged red fibers in two patients with reversible infantile respiratory chain deficiency.
Cotta A et al.·Neuromuscul Disord
2021Case report
Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations.
Dursun F et al.·Eur J Endocrinol
2022Case report
Pathogenic variants in glutamyl-tRNA(Gln) amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.
Friederich MW et al.·Nat Commun
2018
Overexpression of SLC2A1, ALDOC, and PFKFB4 in the glycolysis pathway drives strong drug resistance in 3D HeLa tumor cell spheroids.
Wang T et al.·Biotechnol J
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools