UQCRC2

ubiquinol-cytochrome c reductase core protein 2, the group of M16 metallopeptidases|Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Basic information

Region (hg38): 16:21953288-21983660

Links

ENSG00000140740 ∙ NCBI:7385 ∙ OMIM:191329 ∙ HGNC:12586 ∙ Uniprot:P22695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 5 (Strong), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex III deficiency, nuclear type 5	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	23281071; 33865955

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UQCRC2 gene.

• Mitochondrial complex III deficiency nuclear type 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UQCRC2 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				16		16
missense	1	1	38	1	3	44
nonsense			1			1
start loss						0
frameshift		1	2			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region				8	2	10
non coding			1	28	10	39
Total	1	3	43	45	13

Variants in UQCRC2

This is a list of pathogenic ClinVar variants found in the UQCRC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-21953389-C-T		not specified	Likely benign (May 01, 2017)
16-21953392-G-T		not specified	Benign (Oct 03, 2016)
16-21953402-T-C		not specified	Likely benign (Oct 28, 2016)
16-21953446-G-A		not specified	Uncertain significance (Mar 25, 2024)
16-21953455-C-T			Uncertain significance (Feb 24, 2022)
16-21957058-C-T			Likely benign (Aug 17, 2018)
16-21957068-C-A			Likely benign (Aug 21, 2019)
16-21957068-CA-C			Likely benign (Dec 24, 2019)
16-21957068-C-CA			Benign (Dec 24, 2019)
16-21957215-C-T			Likely benign (Dec 13, 2023)
16-21957227-A-G			Likely benign (Feb 09, 2023)
16-21957253-G-A		not specified	Uncertain significance (Jan 17, 2024)
16-21957263-A-G		not specified	Uncertain significance (Sep 16, 2021)
16-21957281-C-T		not specified	Uncertain significance (Oct 27, 2022)
16-21957296-C-T			Uncertain significance (Aug 16, 2022)
16-21957297-G-A			Likely benign (Dec 22, 2021)
16-21957319-G-T		Mitochondrial complex III deficiency nuclear type 5	Uncertain significance (Apr 04, 2024)
16-21957325-C-T			Likely benign (Mar 22, 2022)
16-21957328-A-G		not specified	Benign/Likely benign (Aug 17, 2023)
16-21957463-A-C			Uncertain significance (Mar 24, 2022)
16-21957505-G-A		Mitochondrial complex III deficiency nuclear type 5	Uncertain significance (Apr 03, 2020)
16-21957526-A-G			Uncertain significance (Nov 24, 2022)
16-21957541-A-G			Uncertain significance (Sep 13, 2022)
16-21957549-C-T		UQCRC2-related disorder	Uncertain significance (Mar 16, 2023)
16-21957550-G-A			Uncertain significance (Feb 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UQCRC2	protein_coding	protein_coding	ENST00000268379	14	31001

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000286	0.984	125714	0	32	125746	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	207	249	0.830	0.0000128	2928
Missense in Polyphen		27	47.131	0.57287		564
Synonymous	0.639	81	88.7	0.914	0.00000452	911
Loss of Function	2.19	13	24.8	0.524	0.00000123	303

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000436	0.000435
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.000436	0.000435
South Asian	0.000131	0.000131
Other	0.000163	0.000163

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. The core protein 2 is required for the assembly of the complex.
• Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 5 (MC3DN5) [MIM:615160]: 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:23281071}. 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: 0.281

Intolerance Scores

• loftool: 0.681
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.27

Haploinsufficiency Scores

• pHI: 0.367
• hipred: Y
• hipred_score: 0.704
• ghis: 0.562

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uqcrc2

Gene ontology

• Biological process: oxidative phosphorylation;protein processing involved in protein targeting to mitochondrion;aerobic respiration
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex III;mitochondrial respiratory chain complex IV;mitochondrial processing peptidase complex;myelin sheath
• Molecular function: endopeptidase activity;protein binding;protein-containing complex binding;metal ion binding