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
mitochondrial complex III deficiency nuclear type 5 (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.

not_provided (97 variants)
not_specified (54 variants)
Mitochondrial_complex_III_deficiency_nuclear_type_5 (14 variants)
UQCRC2-related_disorder (7 variants)
Mitochondrial_disease (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. These statistics are base on transcript: NM_000003366.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				24 clinvar		24
missense	2 clinvar	2 clinvar	69 clinvar	3 clinvar	2 clinvar	78
nonsense			1 clinvar			1
start loss						0
frameshift		3 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)		3 clinvar	2 clinvar			5
Total	2	8	73	27	2

Highest pathogenic variant AF is 0.000008675445

Loading clinvar variants...

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
Phenotype

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