MT-CYB

Chr MT

cytochrome b

Also known as: MTCYB

Cytochrome b is the only mitochondrial DNA-encoded subunit of Complex III of the respiratory chain, serving as the catalytic core for ubiquinol:cytochrome c oxidoreductase activity. Mutations cause Complex III deficiency presenting with exercise intolerance, cardiomyopathy, or MELAS-like syndrome. Inheritance is maternal through the mitochondrial genome, with phenotypic severity depending on the degree of heteroplasmy.

GeneReviewsOMIMResearchSummary from Curated mito context
Multiplemechanism
Clinical SummaryMT-CYB
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Gene-Disease Validity (ClinGen)
mitochondrial disease · MTDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants
51 VUS of 100 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MT-CYB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

Constraint data not available from gnomAD.

DN
0.80top 10%
GOF
0.72top 25%
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

VUS51
Likely Benign16
Benign33
51
VUS
16
Likely Benign
33
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
Likely Pathogenic
0
VUS
51
Likely Benign
16
Benign
33
Total100

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MT-CYB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗