MT-CYB

Chr MT

cytochrome b

Also known as: MTCYB

NCBI Gene: 4519 ENSG00000198727 UniProt: P00156 OMIM: 516020

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.

GeneReviews OMIM ResearchSummary from Curated mito context

Predicted to enable metal ion binding activity. Predicted to contribute to ubiquinol-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, Apr 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— MT-CYB

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Gene-Disease Validity (ClinGen)

mitochondrial disease · MTDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 138 VUS of 331 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MT-CYB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

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

331 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic5

VUS138

Likely Benign67

Benign113

Conflicting1

Likely Pathogenic

138

VUS

Likely Benign

113

Benign

Conflicting

Curated Variants Distribution

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

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	0
Likely Pathogenic	—	—	—	—	5
VUS	—	—	—	—	138
Likely Benign	—	—	—	—	67
Benign	—	—	—	—	113
Conflicting	—				1
Total	—				324

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap MT-CYB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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.

MITOMAP Disease Variants — MT-CYB

MITOMAP ↗

Variant	AA	Disease	Status	GenBank
m.14783T>C	L13L	Possible role in high altitude sickness	Reported	2109.640%
m.14787TTAA>-	frameshift	PD / MELAS	Cfrm [LP]	0.000%
m.14831G>A	A29T	LHON	Reported	18.380%
m.14841A>G	N32S	LHON helper mut.	Reported	3.220%
m.14846G>A	G34S	EXIT / possibly antiatherogenic, poss. myocardial infarction association	Reported [VUS]	0.000%
m.14849T>C	S35P	EXIT / Septo-Optic Dysplasia	Cfrm [VUS*]	0.000%
m.14864T>C	C40R	MELAS	Reported	0.460%
m.14894T>C	F50L	LHON	Reported	1.840%
m.14924T>C	S60P	Mitochondrial neuromuscular disease	Reported	1.070%
m.14970A>G	Y75C	LHON	Reported	1.070%
m.15024G>A	C93Y	Possible DEAF modifier	Reported	6.130%
m.15043G>A	G99G	MDD-associated / possible factor in high altitude sickness / PCOS patient	Reported	2340.620%
m.15059G>A	G105Term	MM / carotid atherosclerosis risk / essential hypertension	Reported	0.000%
m.15060G>A	G105E	Mitochondrial Respiratory Chain Disorder	Reported	0.000%
m.15077G>A	E111K	DEAF / LHON / helper mutation for maternally inherited hypertension / PCOS patient	Reported	24.970%
m.15084G>A	W113Term	EXIT	Reported	0.000%
m.15092G>A	G116S	MELAS	Reported	0.000%
m.15150G>A	W135Term	EXIT	Cfrm [LP]	0.000%
m.15153G>A	G136D	Suspected mito disease	Reported	0.920%
m.15158A>G	M138V	Suspected mito disease	Reported	0.000%
m.15168G>A	W141Term	EXIT	Reported	0.000%
m.15170G>A	G142Term	EXIT	Reported	0.000%
m.15197T>C	S151P	EXIT	Reported [VUS]	0.000%
m.15200G>T	A152S	Possible factor in sepsis	Reported	0.000%
m.15209T>C	Y155H	Prader-Willi syndrome	Reported	1.230%
m.15215G>A	G157Term	MELAS	Reported	0.000%
m.15218A>G	T158A	Possible LHON modulator	Reported	174.160%
m.15234G>A	W163Term	Leigh stroke-like leukodystrophy	Reported	0.000%
m.15236A>G	I164V	Possible LHON helper (one 11778 patient)	Reported	144.750%
m.15237T>C	I164T	Potentially functional variant cosegregating with LHON3635A	Reported	1.070%
m.15242G>A	G166Term	Mitochondrial Encephalomyopathy	Cfrm [LP]	0.000%
m.15243G>A	G166E	HCM	Reported	0.000%
m.15246G>A	G167D	Mitochondrial Respiratory Chain Disorder	Reported	0.000%
m.15256A>G	V170V	Peripheral neuropathy of T2 diabetes	Reported	0.460%
m.15257G>A	D171N	LHON	Conflicting reports	147.660%
m.15287T>C	F181L	Possible DEAF helper mut.	Reported; hg I6a & H10c marker	18.380%
m.15301G>A	L185L	Possible factor in high altitude sickness, LHON	Reported	2814.540%
m.15324C>G	A193G	Possible LHON helper (one 11778 patient)	Reported	0.000%
m.15347C>T	H201Y	HCM +LA +elevated CSF lactate	Reported	0.000%
m.15350G>A	E202K	Possible sepsis factor	Reported	0.000%
m.15395A>G	K217E	Possible LHON factor	Reported	0.460%
m.15436C>A	L230L	Possible role in high altitude sickness	Reported	0.460%
m.15453T>C	L236P	Isolated complex III deficiency	Reported	1.840%
m.15485C>T	P247S	Suspected mitochondrial disorder	Reported	0.000%
m.15497G>A	G251S	EXIT / Obesity	Reported	52.690%
m.1549824bp_deletion>	GDPDNYTL-del	EXIT	Reported	0.000%
m.15498G>A	G251D	DEAF / Infantile histiocytoid cardiomyopathy	Reported	5.360%
m.15579A>G	Y278C	Multisystem Disorder, EXIT	Cfrm [VUS*]	0.000%
m.15615G>A	G290D	EXIT / Antimycin resistance	Reported [VUS]	0.000%
m.15620C>A	L292I	Leigh Syndrome helper mut	Reported	0.000%
m.15635T>C	S297P	Polyvisceral failure / adult Leigh syndrome	Reported	0.310%
m.1564918bp_deletion>	ILAMIP-del	Multisystem Disorder, EXIT	Reported	0.000%
m.15662A>G	I306V	Complex mitochondriopathy-associated	Reported	32.470%
m.15674T>C	S310P	LHON	Reported	29.560%
m.15693T>C	M316T	Possibly LVNC cardiomyopathy-associated	Reported	118.560%
m.15699G>C	R318P	Muscle Weakness SNHL and Migraine	Reported	0.000%
m.15723G>A	W326Term	EXIT	Reported	0.000%
m.15761G>A	G339Term	MM	Reported	0.000%
m.15762G>A	G339E	MM	Reported	0.000%
m.15773G>A	V343M	LHON	Reported - possibly synergistic	12.710%
m.15784T>C	P346P	POAG - potential for association	Reported	334.830%
m.15800C>T	Q352Term	EXIT / Myopathy	Reported	0.000%
m.15804T>C	V353A	Fibromyalgia	Reported	5.970%
m.15812G>A	V356M	LHON	Reported / Secondary	80.720%