MT-CYB

mitochondrially encoded cytochrome b, the group of Mitochondrially encoded protein coding genes|Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Basic information

Region (hg38): M:14747-15887

Previous symbols: [ "MTCYB" ]

Links

ENSG00000198727 ∙ NCBI:4519 ∙ OMIM:516020 ∙ HGNC:7427 ∙ Uniprot:P00156 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoglobinuria, recurrent; Leber hereditary optic neuropathy; Cardiomyopathy, infantile histiocytoid	Maternal	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; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal	6093033; 1732158; 1764087; 9894887; 10502593; 10960495

ClinVar

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

Variants pathogenicity by type

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

Variants in MT-CYB

This is a list of pathogenic ClinVar variants found in the MT-CYB region.

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

Position	Type	Phenotype	Significance	ClinVar
M-14748-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14750-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-14750-A-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-14751-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-14753-C-T		Ovarian neoplasm • not specified	Benign (May 04, 2022)
M-14757-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-14760-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14765-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14766-C-T		Familial cancer of breast • Leigh syndrome • Venous thromboembolism	Benign (Oct 17, 2019)
M-14768-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14769-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-14771-C-A		Autosomal recessive spinocerebellar ataxia 20	Uncertain significance (Dec 22, 2016)
M-14778-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14780-AAATT-A		Parkinsonism/MELAS overlap syndrome • Mitochondrial disease	Likely pathogenic (Dec 11, 2023)
M-14783-T-C		Familial cancer of breast	Benign (Aug 29, 2023)
M-14784-T-C		Ovarian neoplasm • not specified	Benign (May 04, 2022)
M-14786-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14790-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-14792-C-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14793-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-14795-T-C		Leigh syndrome • Leber optic atrophy	Uncertain significance (Sep 27, 2022)
M-14798-T-C		Leigh syndrome	Benign (Oct 17, 2019)
M-14800-C-T		Familial cancer of breast • not specified	Benign (May 04, 2022)
M-14804-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-14813-A-T		Leigh syndrome	Uncertain significance (Oct 17, 2019)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000250|UniProtKB:P00157}.
• Disease: DISEASE: Note=Defects in MT-CYB are a rare cause of mitochondrial dysfunction underlying different myopathies. They include mitochondrial encephalomyopathy, hypertrophic cardiomyopathy (HCM), and sporadic mitochondrial myopathy (MM). In mitochondrial myopathy, exercise intolerance is the predominant symptom. Additional features include lactic acidosis, muscle weakness and/or myoglobinuria. Defects in MTCYB are also found in cases of exercise intolerance accompanied by deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, epilepsy (multisystem disorder). {ECO:0000269|PubMed:11047755, ECO:0000269|PubMed:11601507}.; DISEASE: Cardiomyopathy, infantile histiocytoid (CMIH) [MIM:500000]: A heart disease characterized by the presence of pale granular foamy histiocyte-like cells within the myocardium. It usually affects children younger than 2 years of age, with a clear predominance of females over males. Infants present with dysrhythmia or cardiac arrest. The clinical course is usually fulminant, sometimes simulating sudden infant death syndrome. {ECO:0000269|PubMed:10960495}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. {ECO:0000269|PubMed:1732158}. Note=The disease is caused by mutations affecting distinct genetic loci, including 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)

Haploinsufficiency Scores

• pHI: 0.0907
• ghis: 0.455

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Mouse Genome Informatics

• Gene name: mt-Cytb

Gene ontology

• Biological process: response to hypoxia;mitochondrial electron transport, ubiquinol to cytochrome c;response to heat;electron transport coupled proton transport;animal organ regeneration;response to cobalamin;response to glucagon;hyperosmotic salinity response;response to ethanol;response to cadmium ion;response to copper ion;response to mercury ion;response to calcium ion;response to hyperoxia
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex III;integral component of mitochondrial inner membrane
• Molecular function: ubiquinol-cytochrome-c reductase activity;protein-containing complex binding;metal ion binding