QRSL1

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

Basic information

Region (hg38): 6:106629578-106668417

Links

ENSG00000130348 ∙ NCBI:55278 ∙ OMIM:617209 ∙ HGNC:21020 ∙ Uniprot:Q9H0R6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 40 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 40 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 4	AR	General	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	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic	26741492; 29440775; 30283131

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the QRSL1 gene.

• Combined oxidative phosphorylation deficiency 40 (2 variants)
• Cardiomyopathy, mitochondrial (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the QRSL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	26	5	32
missense	1	1	45	6	3	56
nonsense	1		1			2
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1		2	2	1	6
non coding				5	20	25
Total	2	2	48	37	28

Highest pathogenic variant AF is 0.0000197

Variants in QRSL1

This is a list of pathogenic ClinVar variants found in the QRSL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-106629627-G-A			Benign (May 14, 2021)
6-106629675-G-A			Benign (May 15, 2021)
6-106629691-C-A			Likely benign (Aug 22, 2022)
6-106629691-C-T			Uncertain significance (Jul 04, 2022)
6-106629697-C-T		Combined oxidative phosphorylation deficiency 40 • Inborn genetic diseases	Uncertain significance (Aug 19, 2023)
6-106629702-A-C			Likely benign (Jan 08, 2024)
6-106629703-G-C			Uncertain significance (Nov 08, 2022)
6-106629722-C-T			Benign (Jan 26, 2024)
6-106629725-T-A			Likely benign (Nov 01, 2023)
6-106640356-C-T			Benign (Jan 29, 2024)
6-106640357-G-A			Likely benign (Mar 02, 2023)
6-106640370-G-A		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
6-106640399-A-G			Likely benign (May 16, 2022)
6-106640465-G-A			Likely benign (Oct 26, 2023)
6-106640497-G-T		Combined oxidative phosphorylation deficiency 40	Uncertain significance (Mar 25, 2024)
6-106640501-T-C			Likely benign (Aug 10, 2023)
6-106640505-A-G			Uncertain significance (Feb 09, 2022)
6-106640710-T-A			Benign (May 14, 2021)
6-106640861-G-A			Uncertain significance (Oct 03, 2023)
6-106640862-T-C			Uncertain significance (Aug 22, 2022)
6-106640893-G-A		QRSL1-related disorder	Benign (Jan 18, 2024)
6-106640924-A-G			Uncertain significance (Jul 19, 2022)
6-106641052-TG-T			Benign (May 25, 2021)
6-106642983-A-T			Likely benign (May 30, 2023)
6-106642994-G-A		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
QRSL1	protein_coding	protein_coding	ENST00000369046	11	38840

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.88e-8	0.957	125692	0	56	125748	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	228	278	0.819	0.0000134	3410
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000474	0.000474
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000394	0.000392
Other	0.000489	0.000489

dbNSFP

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}.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);L-glutamine tRNA biosynthesis (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.797
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.16

Haploinsufficiency Scores

• pHI: 0.0990
• hipred: N
• hipred_score: 0.331
• ghis: 0.500

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.483

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Qrsl1

Gene ontology

• Biological process: regulation of protein stability;mitochondrial translation;glutaminyl-tRNAGln biosynthesis via transamidation
• Cellular component: mitochondrion;glutamyl-tRNA(Gln) amidotransferase complex
• Molecular function: amidase activity;protein binding;ATP binding;glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity