UQCRQ

ubiquinol-cytochrome c reductase complex III subunit VII, the group of Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Basic information

Region (hg38): 5:132866630-132868847

Links

ENSG00000164405 ∙ NCBI:27089 ∙ OMIM:612080 ∙ HGNC:29594 ∙ Uniprot:O14949 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex III deficiency nuclear type 4 (Strong), mode of inheritance: AR
• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 4 (Limited), mode of inheritance: Unknown
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex III deficiency, nuclear type 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	Biochemical; Neurologic	18439546
Individuals may suffer acute episodes of metabolic crisis; Treatment with "Mitochondrial cocktail" type therapy may be beneficial

ClinVar

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

• Mitochondrial complex III deficiency nuclear type 4 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UQCRQ 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				6		6
missense	1		14			15
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			35	7	8	50
Total	1	0	50	13	8

Highest pathogenic variant AF is 0.00000656

Variants in UQCRQ

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

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

Position	Type	Phenotype	Significance	ClinVar
5-132866668-TG-T		Mitochondrial complex III deficiency nuclear type 1	Uncertain significance (Jun 14, 2016)
5-132866678-G-C		not specified	Likely benign (Mar 31, 2017)
5-132866683-G-C		Mitochondrial complex III deficiency nuclear type 4	Uncertain significance (Jan 13, 2018)
5-132866685-C-T		Mitochondrial complex III deficiency nuclear type 4	Conflicting classifications of pathogenicity (Jan 12, 2018)
5-132866707-T-C			Benign (Mar 03, 2015)
5-132866719-C-G			Benign (Jun 23, 2018)
5-132866847-C-T			Likely benign (Jul 15, 2018)
5-132866851-C-T		not specified	Likely benign (Jul 25, 2017)
5-132866891-G-A		Mitochondrial complex III deficiency nuclear type 4 • UQCRQ-related disorder	Conflicting classifications of pathogenicity (Dec 05, 2023)
5-132866903-C-A		Mitochondrial complex III deficiency nuclear type 4	Uncertain significance (Jan 27, 2018)
5-132866926-C-T		Mitochondrial complex III deficiency nuclear type 4 • UQCRQ-related disorder	Conflicting classifications of pathogenicity (Dec 13, 2023)
5-132866941-A-G			Likely benign (Aug 04, 2023)
5-132866962-T-C			Likely benign (Dec 11, 2023)
5-132866965-G-T		UQCRQ-related disorder	Likely benign (Feb 23, 2021)
5-132866971-C-G		not specified	Likely benign (Jul 07, 2018)
5-132866971-C-T		Mitochondrial complex III deficiency nuclear type 4	Conflicting classifications of pathogenicity (Jun 03, 2023)
5-132866976-C-T		not specified	Conflicting classifications of pathogenicity (Jul 05, 2022)
5-132866982-G-T		not specified	Uncertain significance (Mar 16, 2022)
5-132866989-C-G		not specified • Mitochondrial complex III deficiency nuclear type 4	Conflicting classifications of pathogenicity (Dec 11, 2023)
5-132866991-A-C			Uncertain significance (Oct 13, 2023)
5-132866991-A-G		not specified	Uncertain significance (May 28, 2024)
5-132866994-T-A		not specified	Uncertain significance (Jun 24, 2022)
5-132866997-T-G			Uncertain significance (Apr 14, 2022)
5-132867015-C-T		Mitochondrial complex III deficiency nuclear type 4	Pathogenic (Jun 16, 2015)
5-132867023-C-T		not specified	Uncertain significance (Jan 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UQCRQ	protein_coding	protein_coding	ENST00000378670	2	1472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0483	0.698	125736	0	4	125740	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.416	42	50.3	0.835	0.00000230	534
Missense in Polyphen		17	15.737	1.0803		176
Synonymous	-0.429	22	19.6	1.12	9.33e-7	159
Loss of Function	0.632	2	3.22	0.620	1.45e-7	33

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This subunit, together with cytochrome b, binds to ubiquinone.
• Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 4 (MC3DN4) [MIM:615159]: A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. {ECO:0000269|PubMed:18439546}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.0550

Intolerance Scores

• loftool: 0.371
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

• pHI: 0.0176
• hipred: Y
• hipred_score: 0.587
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uqcrq

Gene ontology

• Biological process: mitochondrial electron transport, ubiquinol to cytochrome c;subthalamus development;pons development;cerebellar Purkinje cell layer development;hippocampus development;thalamus development;hypothalamus development;pyramidal neuron development;midbrain development
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex III
• Molecular function: ubiquinol-cytochrome-c reductase activity