MT-CYB
protein-codingmitochondrially encoded cytochrome b, the group of Mitochondrially encoded protein coding genes|Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits
Gene summary
Predicted to enable electron transfer activity; metal ion binding activity; and oxidoreductase activity. Predicted to contribute to quinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrial inner membrane. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Jun 2026]
- MTCYB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Mitochondrial
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *MT-CYB* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of March 4, 2024. The *MT-CYB* gene encodes cytochrome b, the core catalytic subunit of respiratory chain complex III (ubiquinone: cytochrome c oxidoreductase). Defects in this gene lead to isolated complex III deficiency. The *MT-CYB* gene was first reported in relation to maternally inherited primary mitochondrial disease in 1996 (PMID: 8910895), in an adult male with a childhood onset of progressive exercise intolerance. Subsequent publications reported additional individuals with a progressive exercise as well as progressive multisystem disease manifestations (encephalopathy, headaches, ataxia, hearing loss, cataracts, retinal dystrophy, ophthalmoplegia, epilepsy, nausea, vomiting, Wolff-Parkinson-White arrhythmia). In most cases, affected individuals had elevated lactate levels with muscle biopsies revealing an isolated complex III deficiency and ragged red fibers. While various names have been given to the constellation of features seen in those with *MT-CYB*-related disease, pathogenic variants in this gene cause a primary mitochondrial disease. Therefore, the *MT-CYB* phenotype has been lumped into one disease entity according to the ClinGen Lumping and Splitting Framework. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included 12 unique variants reported in 12 cases from eight publications (PMIDs: 8910895, 11047755, 12686403, 11464242, 10502593, 9894887, 11601507, 9894888). Variants included six nonsense (m.15059G>A, m.15150G>A, m.15168G>A, m.15242G>A, m.15761G>A, m.15084G>A), one frameshift (m.14787_14790delTTAA), one in-frame deletion (m.15498-15521del24), and four missense variants (m.14846G>A, m.15197T>C , m.15579A>G, m.15615G>A). Cybrids studies (PMIDs: 24863938, 11601507) and single fiber testing (PMIDs: 9894887, 10502593, 11047755) further supported the pathogenicity of several of these variants. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416). In summary, there is definitive evidence to support the relationship between *MT-CYB* and primary mitochondrial disease. This relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on March 4, 2024, (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0015448
Submitter: Orphanet
Inheritance Pattern: Mitochondrial
Disease ID:MONDO:0010788
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic; Renal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MT-CYB variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 0 | 0 | 0 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| Ensembl | ENSP00000354554.2 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- response to hypoxia
- mitochondrial electron transport, ubiquinol to cytochrome c
- response to heat
- electron transport coupled proton transport
- animal organ regeneration
Molecular Function
- ubiquinol-cytochrome-c reductase activity
- protein-containing complex binding
- metal ion binding
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- mitochondrial respiratory chain complex III
- integral component of mitochondrial inner membrane
dbNSFP Gene Annotations
Source:
- 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.;
Essentials
- Indispensability pred.
- N
- Indispensability score
- 0.114