QRSL1

protein-coding

glutaminyl-tRNA amidotransferase subunit QRSL1, the group of Glutamyl-tRNA amidotransferase subunits

Gene summary

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]

MANE transcript

NM_018292.5

Inheritance

ClinVar variants

P:12U:86B:49

Top phenotype

Combined oxidative phosphorylation deficiency 4

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr6:106,629,578-106,668,417

External References & Databases

Ensembl (ENSG00000130348)

Transcript & Mutation Effects

hg38 • Region Span ~38.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

combined oxidative phosphorylation deficiency 40LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030006

Submitter: Ambry Genetics

combined oxidative phosphorylation deficiency 40STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030006

Submitter: PanelApp Australia

combined oxidative phosphorylation deficiency 40STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030006

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Combined oxidative phosphorylation deficiency 4AR

Manifestation: Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26741492; 29440775; 30283131

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to QRSL1 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 105

Inborn genetic diseasesTotal: 55

not specifiedTotal: 17

QRSL1-related disorderTotal: 12

Combined oxidative phosphorylation deficiency 40Total: 11

Cardiomyopathy, mitochondrialTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018292.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	38 clinvar	2 clinvar	42
missense	2 clinvar	2 clinvar	77 clinvar	9 clinvar		90
nonsense	2 clinvar		2 clinvar			4
start loss						0
frameshift	3 clinvar	2 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	7	5	86	47	2	147

Highest pathogenic variant AF is 0.000031818534

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018292.5	RefSeq	NP_060762.3	11	MANE Select
ENST00000369046.8	Ensembl	ENSP00000358042.4	11	MANE Select
ENST00000369044.1	Ensembl	ENSP00000358040.1	7	Standard
ENST00000369044.2	Ensembl	ENSP00000358040.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aminoacyl-tRNA biosynthesis - Homo sapiens (human)
L-glutamine tRNA biosynthesis

Biological Process

regulation of protein stability
mitochondrial translation
glutaminyl-tRNAGln biosynthesis via transamidation

Molecular Function

amidase activity
protein binding
ATP binding
glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity

Cellular Component

mitochondrion
glutamyl-tRNA(Gln) amidotransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369046
Coding exons: 11
Length: 38840
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125748
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	228	278	0.819	0.0000134	3410
Missense (PolyPhen)		67	109.81	0.61014		1388
Synonymous	-0.586	111	103	1.07	0.00000519	1043
Loss of Function	1.99	16	27.2	0.588	0.00000143	338

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.00039	0.00039	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu- tRNA(Gln). {ECO:0000255|HAMAP-Rule:MF_03150, ECO:0000269|PubMed:19805282}.;
Disease: DISEASE: Note=Defects in QRSL1 may play a role in mitochondrial disorders characterized by combined respiratory chain complex deficiencies. {ECO:0000269|PubMed:26741492}.;

Recessive Scores

pRec: 0.193

Intolerance Scores

LoFtool: 0.797
RVIS EVS: 0.42
RVIS percentile EVS: 77.16

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.483

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium