UQCRFS1

ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1, the group of Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Basic information

Region (hg38): 19:29205320-29213151

Links

ENSG00000169021 ∙ NCBI:7386 ∙ OMIM:191327 ∙ HGNC:12587 ∙ Uniprot:P47985 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 3 deficiency, nuclear type 10 (Limited), mode of inheritance: AR
• mitochondrial complex 3 deficiency, nuclear type 10 (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 10	AR	Biochemical; Cardiovascular	Individuals have been described as benefitting from medical management (with coenzyme Q10 supplementation); Individuals have been described with cardiomyopathy, and awareness may allow early detection and management	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Neurologic	31883641

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UQCRFS1 gene.

• Mitochondrial complex 3 deficiency, nuclear type 10 (3 variants)
• Propionic acidemia;Lactic acidosis;Cardiomyopathy (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UQCRFS1 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				2	2	4
missense	1		7	2	1	11
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding						0
Total	3	0	7	4	3

Variants in UQCRFS1

This is a list of pathogenic ClinVar variants found in the UQCRFS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-29207587-C-T			Likely benign (Nov 01, 2022)
19-29207588-G-A		not specified	Uncertain significance (Dec 14, 2021)
19-29207742-C-G		not specified	Uncertain significance (Feb 13, 2024)
19-29207763-G-A		Propionic acidemia;Lactic acidosis;Cardiomyopathy • Mitochondrial complex 3 deficiency, nuclear type 10	Pathogenic (Feb 27, 2019)
19-29207854-G-C			Likely benign (Mar 01, 2022)
19-29207902-G-A			Benign (May 16, 2018)
19-29207964-C-T		not specified	Likely benign (Oct 14, 2023)
19-29207997-C-G		not specified	Uncertain significance (Jan 26, 2022)
19-29208059-T-C		not specified	Uncertain significance (Mar 20, 2024)
19-29208140-T-A		not specified	Uncertain significance (Feb 17, 2023)
19-29208159-C-G		Propionic acidemia;Lactic acidosis;Cardiomyopathy • Mitochondrial complex 3 deficiency, nuclear type 10	Pathogenic (Feb 27, 2019)
19-29212968-T-A		not specified	Likely benign (Apr 12, 2022)
19-29212994-A-T		not specified	Uncertain significance (Feb 28, 2023)
19-29213078-A-T		Propionic acidemia;Lactic acidosis;Cardiomyopathy • Mitochondrial complex 3 deficiency, nuclear type 10	Pathogenic (Feb 27, 2019)
19-29213082-G-C		not specified	Uncertain significance (Jan 25, 2023)
19-29213095-T-C		Mitochondrial complex 3 deficiency, nuclear type 10	Benign (Dec 05, 2021)
19-29213103-A-C		Mitochondrial complex 3 deficiency, nuclear type 10	Benign (Dec 05, 2021)
19-29213114-A-G		not specified	Uncertain significance (Mar 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UQCRFS1	protein_coding	protein_coding	ENST00000304863	2	6276

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.189	0.766	125357	0	2	125359	0.00000798

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	75	135	0.556	0.00000721	1718
Missense in Polyphen		27	66.207	0.40781		779
Synonymous	0.0250	55	55.2	0.996	0.00000315	590
Loss of Function	1.67	2	6.63	0.302	3.44e-7	99

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000645	0.0000623
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochrome b-c1 complex subunit Rieske, mitochondrial: Component of the mitochondrial ubiquinol-cytochrome c reductase complex dimer (complex III dimer), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis (PubMed:28673544). Incorporation of UQCRFS1 is the penultimate step in complex III assembly (PubMed:28673544). {ECO:0000269|PubMed:28673544}.
• 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: 0.220

Intolerance Scores

• loftool: 0.249
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.616
• hipred: Y
• hipred_score: 0.656
• ghis: 0.631

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uqcrfs1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: mitochondrial electron transport, ubiquinol to cytochrome c;response to hormone;response to drug;response to antibiotic
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex III;mitochondrial respiratory chain complex IV;integral component of membrane
• Molecular function: protein binding;ubiquinol-cytochrome-c reductase activity;protein-containing complex binding;metal ion binding;2 iron, 2 sulfur cluster binding