MT-CYB

Summary

MT-CYB (mitochondrially encoded cytochrome b, HGNC:7427) is a protein-coding gene on chromosome mitochondria, encoding Cytochrome b (P00156). Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain.

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.

Source: NCBI Gene 4519 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 334 total — 5 likely-pathogenic
• Phenotypes (HPO): 91

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7427
Approved symbol	MT-CYB
Name	mitochondrially encoded cytochrome b
Location	mitochondria
Locus type	gene with protein product
Status	Approved
Aliases	COB, CYTB, UQCR3
Ensembl gene	ENSG00000198727
Ensembl biotype	protein_coding
OMIM	516020
Entrez	4519

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361789

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000361789 — 1 exons

Exon	Start	End
ENSE00001436074	14747	15887

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 653.7413 / max 177422.2063, expressed in 1822 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195035	225.4915	1804
195042	151.9996	1787
195032	151.1108	1795
195034	62.7783	1776
195033	16.0138	1617
195039	12.8447	1468
195036	10.1428	1442
195041	7.5448	1086
195040	6.3710	1128
195037	5.0124	1143

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.99	gold quality
pituitary gland	UBERON:0000007	99.98	gold quality
zone of skin	UBERON:0000014	99.98	gold quality
adult mammalian kidney	UBERON:0000082	99.98	gold quality
endocervix	UBERON:0000458	99.98	gold quality
adipose tissue	UBERON:0001013	99.98	gold quality
rectum	UBERON:0001052	99.98	gold quality
right lobe of liver	UBERON:0001114	99.98	gold quality
right lobe of thyroid gland	UBERON:0001119	99.98	gold quality
smooth muscle tissue	UBERON:0001135	99.98	gold quality
transverse colon	UBERON:0001157	99.98	gold quality
fundus of stomach	UBERON:0001160	99.98	gold quality
mucosa of stomach	UBERON:0001199	99.98	gold quality
cortex of kidney	UBERON:0001225	99.98	gold quality
right adrenal gland	UBERON:0001233	99.98	gold quality
left adrenal gland	UBERON:0001234	99.98	gold quality
right uterine tube	UBERON:0001302	99.98	gold quality
left uterine tube	UBERON:0001303	99.98	gold quality
gastrocnemius	UBERON:0001388	99.98	gold quality
skin of abdomen	UBERON:0001416	99.98	gold quality
skin of leg	UBERON:0001511	99.98	gold quality
right coronary artery	UBERON:0001625	99.98	gold quality
left coronary artery	UBERON:0001626	99.98	gold quality
temporal lobe	UBERON:0001871	99.98	gold quality
caudate nucleus	UBERON:0001873	99.98	gold quality
putamen	UBERON:0001874	99.98	gold quality
amygdala	UBERON:0001876	99.98	gold quality
nucleus accumbens	UBERON:0001882	99.98	gold quality
hypothalamus	UBERON:0001898	99.98	gold quality
Ammon’s horn	UBERON:0001954	99.98	gold quality

Single-cell (SCXA)

Detected in 66 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	42678.60
E-CURD-122	yes	31418.44
E-GEOD-149689	yes	30731.99
E-HCAD-36	yes	29421.52
E-CURD-98	yes	22463.13
E-MTAB-6701	yes	22140.56
E-MTAB-8322	yes	21022.68
E-MTAB-6505	yes	18972.68
E-HCAD-6	yes	18873.36
E-MTAB-8884	yes	16127.57
E-MTAB-8207	yes	15650.88
E-GEOD-124472	yes	13336.22
E-MTAB-7407	yes	12813.66
E-MTAB-8221	yes	12588.34
E-MTAB-8142	yes	12577.67

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 22)

• The other proband had a non-synonymous G15221A mutation in the cytochrome b gene. (PMID:12031626)
• In a mitochondrial myopathy patient, a novel stop-codon mutation (G15761A) was found in the mitochondrial DNA (mtDNA)-encoded cytochrome b gene, resulting in loss of the last 41 amino acids of the protein and complex III deficiency (PMID:12686403)
• clinical/phenotypic variability of the G15498A mutation in mitochondrial DNA (PMID:14735157)
• biochemical and molecular genetic studies of a patient with both muscle and brain involvement and a severe reduction in the activities of both complexes I and III in skeletal muscle due to a novel mutation in the MTCYB gene (PMID:16008558)
• caspase 8-dependent cleavage of mitochondrial Cyt b and translocation of its C-terminal half into the cytoplasm occurred during FAS-induced apoptosis in both chicken and human cells (PMID:18796602)
• mitocryptide-2 (MCT-2) and its human homolog hMCT-2 are cryptides that activate neutrophils (PMID:19342687)
• CytbI7T has a role in longevity related to caloric restriction (PMID:19503808)
• The m.15635T>C transition (S297P) was carried by a newborn who presented with a polyvisceral failure. (PMID:19563916)
• cytochrome B gene mutation induces mitochondrial proliferation and prevents apoptosis in human uroepithelial SV-HUC-1 cells. (PMID:19569044)
• Trx2 overexpression modulates the mRNA levels of the COX1 (cytochrome oxidase subunit I) and Cytb (cytochrome b), which are known to be regulated by GR and NF-kappaB. (PMID:19570036)
• Data show that homoplasmic G6709A (MT-CO1) and G14804A (MT-CYB) alterations cause amino acid changes in the highly conserved residues. (PMID:21389643)
• Significant elevation of ERalpha and MTCYB transcript levels in premenopausal leiomyomas and its association with ERalpha, -397 CC genotype suggests the mitochondrial-mediated role of estrogen as the promoter of leiomyoma tumorigenesis. (PMID:21506659)
• This study suggests that, in part, polymorphisms in the MT-ATP6 and MT-CYB genes may contribute to the unexpected fertilization failure. (PMID:24102627)
• The polymorphisms of CYTB as a very useful DNA marker were significantly different between different geographical Uyghur (PMID:24103151)
• Mitochondrial mutation m.15804T>C in the mtCYB gene in a family with fibromyalgia is associated with NLRP3-inflammasome activation. (PMID:26566881)
• These results indicate that miR-151a-5p may participate in the regulation of cellular respiration and ATP production through targeting Cytb. (PMID:26626315)
• The effects of mutation in mitochondrially encoded cytochrome b are reviewed. (PMID:28132468)
• The heteroplasmy level of some mutations in gene MT-CYB among women with asymptomatic atherosclerosis (PMID:29368910)
• Liver mitochondrial DNA damage and genetic variability of Cytochrome b - a key component of the respirasome - drive the severity of fatty liver disease. (PMID:32634278)
• Association between the single nucleotide variants of the mitochondrial cytochrome B gene (MT-CYB) and the male infertility. (PMID:35118571)
• Mitochondrial Genome-Encoded Long Noncoding RNA Cytochrome B and Mitochondrial Dysfunction in Diabetic Retinopathy. (PMID:37464864)
• Single nucleotide polymorphism rs527236194 of the cytochrome B gene (MT-CYB) is associated with alterations in sperm parameters. (PMID:37921983)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt-cyb	ENSDARG00000063924
mus_musculus	mt-Cytb	ENSMUSG00000064370
rattus_norvegicus	Mt-cyb	ENSRNOG00000031766
drosophila_melanogaster	mt:Cyt-b	FBGN0013678
caenorhabditis_elegans		WBGENE00000829

Protein

Protein identifiers

Cytochrome b — P00156 (reviewed: P00156)

Alternative names: Complex III subunit 3, Complex III subunit III, Cytochrome b-c1 complex subunit 3, Ubiquinol-cytochrome-c reductase complex cytochrome b subunit

All UniProt accessions (2): P00156, Q0ZFD6

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. The cytochrome bc1 complex contains 11 subunits: 3 respiratory subunits (MT-CYB, CYC1 and UQCRFS1), 2 core proteins (UQCRC1 and UQCRC2) and 6 low-molecular weight proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of UQCRFS1). This cytochrome bc1 complex then forms a dimer.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. 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, intellectual disability, retinitis pigmentosa, cataract, growth retardation, epilepsy (multisystem disorder). 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. The disease is caused by variants affecting the gene represented in this entry. Leber hereditary optic neuropathy (LHON) [MIM:535000] A maternally inherited form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. Cardiac conduction defects and neurological defects have also been described in some LHON patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

Cofactor. Binds 2 heme b groups non-covalently.

Miscellaneous. Heme 1 (or BL or b562) is low-potential and absorbs at about 562 nm, and heme 2 (or BH or b566) is high-potential and absorbs at about 566 nm.

Similarity. Belongs to the cytochrome b family.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005797	Cyt_b/b6_N	Domain
IPR005798	Cyt_b/b6_C	Domain
IPR016174	Di-haem_cyt_TM	Homologous_superfamily
IPR027387	Cytb/b6-like_sf	Homologous_superfamily
IPR030689	Cytochrome_b	Family
IPR036150	Cyt_b/b6_C_sf	Homologous_superfamily
IPR048259	Cytochrome_b_N_euk/bac	Domain
IPR048260	Cytochrome_b_C_euk/bac	Domain

Pfam: PF00032, PF00033

UniProt features (85 total): sequence variant 41, helix 21, transmembrane region 8, strand 6, binding site 5, turn 3, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9HZL	ELECTRON MICROSCOPY	2.52
9CG3	ELECTRON MICROSCOPY	2.96
5XTE	ELECTRON MICROSCOPY	3.4
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00156-F1	97.77	0.99

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 97 (axial binding residue); 182 (axial binding residue); 196 (axial binding residue); 201; 83 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5419276	Mitochondrial translation termination
R-HSA-611105	Respiratory electron transport
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 308 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGENERATION, GOBP_RESPONSE_TO_COPPER_ION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_RESPONSE_TO_GLUCAGON, GOBP_MITOCHONDRIAL_ELECTRON_TRANSPORT_UBIQUINOL_TO_CYTOCHROME_C, GOBP_RESPONSE_TO_INCREASED_OXYGEN_LEVELS, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_ELECTRON_TRANSPORT_CHAIN, KEGG_HUNTINGTONS_DISEASE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (20): response to hypoxia (GO:0001666), mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122), response to xenobiotic stimulus (GO:0009410), response to toxic substance (GO:0009636), electron transport coupled proton transport (GO:0015990), animal organ regeneration (GO:0031100), response to cobalamin (GO:0033590), response to glucagon (GO:0033762), cellular respiration (GO:0045333), response to ethanol (GO:0045471), response to cadmium ion (GO:0046686), response to copper ion (GO:0046688), response to mercury ion (GO:0046689), response to calcium ion (GO:0051592), response to hyperoxia (GO:0055093), response to D-galactosamine (GO:1904421), response to nutrient (GO:0007584), response to hormone (GO:0009725), electron transport chain (GO:0022900), respiratory electron transport chain (GO:0022904)

GO Molecular Function (5): quinol-cytochrome-c reductase activity (GO:0008121), oxidoreductase activity (GO:0016491), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), electron transfer activity (GO:0009055)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), respiratory chain complex III (GO:0045275), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	1
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	4
response to metal ion	4
response to stress	2
response to oxygen-containing compound	2
response to decreased oxygen levels	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
energy coupled proton transmembrane transport, against electrochemical gradient	1
regeneration	1
animal organ development	1
response to vitamin	1
response to nitrogen compound	1
response to peptide hormone	1
energy derivation by oxidation of organic compounds	1
response to alcohol	1
response to increased oxygen levels	1
response to nutrient levels	1
response to endogenous stimulus	1
generation of precursor metabolites and energy	1
electron transport chain	1
cellular respiration	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on diphenols and related substances as donors	1
active monoatomic ion transmembrane transporter activity	1
catalytic activity	1
binding	1
cation binding	1
molecular_function	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1
cellular_component	1

Protein interactions and networks

STRING

3260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT-CYB	UQCRFS1	P47985	999
MT-CYB	CYC1	P08574	999
MT-CYB	CYCS	P00001	992
MT-CYB	UQCRB	P14927	984
MT-CYB	BFSP2	Q13515	976
MT-CYB	MT-ATP6	P00846	973
MT-CYB	MT-ND5	P03915	972
MT-CYB	MT-ND4L	P03901	971
MT-CYB	MT-CO1	P00395	970
MT-CYB	MB	P02144	968
MT-CYB	UQCRQ	O14949	968
MT-CYB	MT-ND4	P03905	963
MT-CYB	MT-CO3	P00414	960
MT-CYB	MT-ND2	P03891	960
MT-CYB	MT-ND6	P03923	959

IntAct

26 interactions, top by confidence:

A	B	Type	Score
UQCRQ	COX7A2L	psi-mi:“MI:0914”(association)	0.640
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS8	psi-mi:“MI:0914”(association)	0.530
MRPL50	GTPBP10	psi-mi:“MI:0914”(association)	0.530
UQCRH	DCTN6	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MT-CYB	E6	psi-mi:“MI:0915”(physical association)	0.370
MVP	MT-CYB	psi-mi:“MI:0915”(physical association)	0.370
KRAS	MT-CYB	psi-mi:“MI:0915”(physical association)	0.370
CLDND1	MAN1A2	psi-mi:“MI:0914”(association)	0.350
UQCRH	SSC5D	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
CCR6	GPR89A	psi-mi:“MI:0914”(association)	0.350
KDSR	ACOT7	psi-mi:“MI:0914”(association)	0.350
UQCR10	COX7A2L	psi-mi:“MI:0914”(association)	0.350
PTGES2	COX7A2L	psi-mi:“MI:0914”(association)	0.350
UQCRC2	COX7A2L	psi-mi:“MI:0914”(association)	0.350
BORCS6	UQCRQ	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): CYTB (Affinity Capture-MS), CYTB (Co-fractionation), CYTB (Co-fractionation), CYTB (Two-hybrid), CYTB (Affinity Capture-MS), CYTB (Affinity Capture-MS), CYTB (Affinity Capture-MS), CYTB (Affinity Capture-MS), CYTB (Affinity Capture-MS), CYTB (Affinity Capture-MS), CYTB (Proximity Label-MS), CYTB (Proximity Label-MS), CYTB (Proximity Label-MS), CYTB (Proximity Label-MS), CYTB (Affinity Capture-MS)

ESM2 similar proteins: O03812, O47890, O47892, O47893, O48321, P00156, P41290, P92657, Q20FQ1, Q20FQ2, Q20FQ7, Q20FR3, Q20FR8, Q20K40, Q20K43, Q2Y060, Q597C7, Q597E3, Q597E4, Q597E6, Q597E8, Q5VJ41, Q5VJ46, Q5VJ49, Q5VJ50, Q5VJ61, Q6KF39, Q6KF53, Q70RT7, Q70RW3, Q7Y8J5, Q8LWN0, Q8SJK5, Q8SJK6, Q8SJK8, Q8SJK9, Q8SJL1, Q8SJL2, Q8SJL3, Q95711

Diamond homologs: A0PH66, O03363, O21411, O21416, O21804, O47421, O47557, O47560, O47561, O47890, O47892, O47893, O48321, O63699, O78742, O78773, O78785, O78789, O78927, O78928, O78934, O79360, O79445, O79447, O79450, P00156, P92701, Q1XIK9, Q1XIM5, Q2TVN1, Q2Y060, Q2Y067, Q33500, Q34101, Q34900, Q35438, Q35614, Q35677, Q3ZED1, Q4VWH4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MT-CYB	“form complex”	“CoQ-cytochrome c reductase-Mitochondrial respiratory chain complex III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex III assembly	6	131.8×	2e-10
Respiratory electron transport	9	42.8×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
cellular respiration	5	98.2×	8e-08
aerobic respiration	5	56.3×	9e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

334 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	5
Uncertain significance	139
Likely benign	57
Benign	115

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2687510	NC_012920.1(MT-CYB):m.15215G>A	Likely pathogenic
4795908	NC_012920.1(MT-CYB):m.15041G>A	Likely pathogenic
9680	NC_012920.1(MT-CYB):m.15242G>A	Likely pathogenic
9681	NC_012920.1(MT-CYB):m.15150G>A	Likely pathogenic
9686	NC_012920.1(MT-CYB):m.14783TTAA[1]	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2427 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
M:15128:T:C	F128L	0.992
M:15130:C:A	F128L	0.992
M:15130:C:G	F128L	0.992
M:15560:T:C	W272R	0.989
M:14868:T:C	L41P	0.987
M:14933:T:C	F63L	0.986
M:14935:T:A	F63L	0.986
M:14935:T:G	F63L	0.986
M:15591:G:C	R282P	0.986
M:15045:G:C	R100P	0.985
M:15167:T:C	W141R	0.985
M:15169:A:C	W141C	0.985
M:15169:A:T	W141C	0.985
M:14837:T:C	W31R	0.984
M:15290:C:G	H182D	0.984
M:15023:T:C	C93R	0.982
M:15170:G:T	G142W	0.982
M:15588:T:A	L281H	0.982
M:14888:G:T	G48W	0.981
M:15083:T:C	W113R	0.980
M:15555:C:A	P270H	0.979
M:15427:A:C	K227N	0.978
M:15427:A:T	K227N	0.978
M:15276:G:C	R177P	0.976
M:15293:T:C	F183L	0.976
M:15295:C:A	F183L	0.976
M:15295:C:G	F183L	0.976
M:14864:T:C	C40R	0.975
M:15162:C:G	S139W	0.975
M:15588:T:C	L281P	0.975

dbSNP variants (sampled 300 via entrez): RS1057516069 (MT:14563 C>T), RS1057516070 (MT:14706 A>G), RS1057516071 (MT:14854 C>T), RS1057516072 (MT:15060 G>A), RS1057516073 (MT:15096 T>C), RS1057516074 (MT:15127 C>T), RS1057516075 (MT:15246 G>A), RS1057518823 (MT:15446 C>T), RS1057518882 (MT:14598 T>C), RS1057520097 (MT:15262 T>C), RS1057520103 (MT:14476 G>A,T), RS1057520206 (MT:15848 A>G), RS1131692063 (MT:13051 G>A,T), RS117017250 (MT:16360 C>T), RS117565943 (MT:16051 A>G)

Disease associations

OMIM: gene MIM:516020 | disease phenotypes: MIM:535000, MIM:540000, MIM:256000, MIM:114480, MIM:545000, MIM:530000, MIM:551500, MIM:616354, MIM:500009, MIM:500000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber hereditary optic neuropathy	Supportive	Mitochondrial
mitochondrial complex III deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Definitive	MT

Mondo (23): Leber hereditary optic neuropathy (MONDO:0010788), MELAS syndrome (MONDO:0010789), venous thromboembolism (MONDO:0005399), Leigh syndrome (MONDO:0009723), hereditary breast carcinoma (MONDO:0016419), mitochondrial disease (MONDO:0044970), ovarian neoplasm (MONDO:0021068), MERRF syndrome (MONDO:0010790), progressive external ophthalmoplegia (MONDO:0005181), Kearns-Sayre syndrome (MONDO:0010787), NARP syndrome (MONDO:0010794), epilepsy (MONDO:0005027), inborn mitochondrial myopathy (MONDO:0009637), sensorineural hearing loss disorder (MONDO:0020678), hearing loss disorder (MONDO:0005365)

Orphanet (15): Leber hereditary optic neuropathy (Orphanet:104), MELAS (Orphanet:550), Hereditary breast cancer (Orphanet:227535), Leigh syndrome (Orphanet:506), Mitochondrial disease (Orphanet:68380), MERRF (Orphanet:551), Kearns-Sayre syndrome (Orphanet:480), Progressive external ophthalmoplegia (Orphanet:520820), NARP syndrome (Orphanet:644), Mitochondrial myopathy (Orphanet:206966), Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome (Orphanet:397709), Mitochondrial myopathy with reversible cytochrome C oxidase deficiency (Orphanet:254864), Histiocytoid cardiomyopathy (Orphanet:137675), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

91 total (30 of 91 shown, HPO-id order):

HPO	Term
HP:0000107	Renal cyst
HP:0000147	Polycystic ovaries
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000408	Progressive sensorineural hearing impairment
HP:0000485	Megalocornea
HP:0000512	Abnormal electroretinogram
HP:0000519	Developmental cataract
HP:0000529	Progressive visual loss
HP:0000551	Color vision defect
HP:0000568	Microphthalmia
HP:0000572	Visual loss
HP:0000576	Centrocecal scotoma
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000622	Blurred vision
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000726	Dementia
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000961	Cyanosis
HP:0000980	Pallor
HP:0001112	Leber optic atrophy
HP:0001138	Optic neuropathy
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001254	Lethargy
HP:0001269	Hemiparesis
HP:0001271	Polyneuropathy

GWAS associations

0 associations (top):

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D007625	Kearns-Sayre Syndrome	C05.651.460.700.500; C10.292.562.750.250.500; C10.597.622.447.511.500; C10.668.491.500.700.500; C11.590.472.250.500; C11.768.585.658.500.627; C14.280.238.510; C18.452.660.560.700.500; C23.550.291.500.688.500; C23.888.592.636.447.511.500
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
D017241	MELAS Syndrome	C05.651.460.620.520; C10.228.140.163.100.535; C10.228.140.300.275.500; C10.668.491.500.500.500; C14.907.253.329.500; C16.320.565.189.535; C18.452.132.100.535; C18.452.648.189.535; C18.452.660.560.620.520
D017243	MERRF Syndrome	C05.651.460.620.530; C10.228.140.163.100.545; C10.228.140.490.375.130.650.700; C10.228.140.490.493.063.650.700; C10.668.491.500.500.550; C16.320.565.189.545; C18.452.132.100.545; C18.452.648.189.545; C18.452.660.560.620.530
D017237	Mitochondrial Encephalomyopathies	C05.651.460.620; C10.228.140.163.540; C10.668.491.500.500; C18.452.132.540; C18.452.660.560.620
D017240	Mitochondrial Myopathies	C05.651.460; C10.668.491.500; C18.452.660.560
D017246	Ophthalmoplegia, Chronic Progressive External	C05.651.460.700; C10.292.562.750.250; C10.597.622.447.511; C10.668.491.500.700; C11.590.472.250; C18.452.660.560.700; C23.550.291.500.688; C23.888.592.636.447.511
D029242	Optic Atrophy, Hereditary, Leber	C10.292.700.225.500.400; C10.574.500.662.400; C11.270.564.400; C11.640.451.451.400; C16.320.290.564.400; C16.320.400.630.400; C18.452.660.670
D054556	Venous Thromboembolism	C14.907.355.590.700
C562840	Breast Cancer, Familial (supp.)
C535584	Cardiomyopathy, infantile histiocytoid (supp.)
C537396	Neuropathy ataxia and retinitis pigmentosa (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PubChem BioAssay actives

19 with measured affinity, of 106 total; 19 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(2R,3S,6S,7R)-3-[(3-formamido-2-hydroxybenzoyl)amino]-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl] 3-methylbutanoate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	0.0070	uM
methyl 2-[3-[5-(3-cyclohexylpropoxy)-2-fluorophenyl]-7-methylindazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	0.7902	uM
methyl 2-[3-[3-(cyclohexylmethoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	0.8890	uM
methyl 2-[3-[2-fluoro-5-(trifluoromethyl)phenyl]-7-methylindazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	1.0440	uM
methyl 2-[3-[3-[2-(1-adamantyl)ethoxy]phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	1.0800	uM
methyl 2-[3-[3-(2-phenylethyl)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	1.1730	uM
methyl 2-[3-(2-fluoro-5-phenylmethoxyphenyl)indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	1.6640	uM
3-[4-(4-chlorophenyl)cyclohexyl]-4-hydroxynaphthalene-1,2-dione	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	1.8800	uM
methyl 2-[3-[5-(3-cyclohexylpropoxy)-2-fluorophenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	2.4300	uM
3-[5-(3-cyclohexylpropoxy)-2-fluorophenyl]-7-methyl-1-[(2-methyltetrazol-5-yl)methyl]indazole	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	2.9170	uM
methyl 2-[3-[3-(2-cyclohexylethoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	3.2340	uM
methyl 2-[3-[2-fluoro-5-(trifluoromethyl)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	4.6220	uM
methyl 2-[3-[3-(3,3-dimethylbutoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	4.7150	uM
methyl 2-[3-[3-(3-methylbutoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	4.7680	uM
methyl 2-[3-[3-(3-cyclohexylpropoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	5.4650	uM
3-[2-fluoro-5-(trifluoromethyl)phenyl]-7-methyl-1-[(2-methyltetrazol-5-yl)methyl]indazole	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	6.5070	uM
methyl 2-[3-[3-(trifluoromethyl)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	8.6550	uM
methyl 2-[3-[3-(2-methylpropoxy)phenyl]indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	9.2320	uM
methyl 2-[3-(3-phenoxyphenyl)indazol-1-yl]acetate	1801889: Cytochrome b Enzyme Assay from Article 10.1016/j.chembiol.2016.06.016: “A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.”	ic50	9.9740	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	5
Particulate Matter	decreases expression, increases abundance	4
bisphenol A	decreases expression, decreases reaction, increases abundance	2
enniatins	decreases expression	2
Atrazine	decreases expression	2
1-Methyl-4-phenylpyridinium	decreases reaction, decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
beauvericin	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
versicolorin A	decreases expression	1
2-chloroethyl ethyl sulfide	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
fialuridine	decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
sarpogrelate	decreases reaction, increases reaction, decreases expression	1
azoxystrobin	decreases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	decreases reaction, decreases expression	1
MitoTEMPO	decreases expression, decreases reaction	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbon Tetrachloride	decreases expression, decreases reaction, increases reaction, affects reaction	1
Clorgyline	decreases expression, decreases reaction, increases reaction	1
Doxorubicin	decreases expression	1
Dust	decreases expression, increases abundance	1
Ethidium	decreases expression	1

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 2 finite cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0332	Hs 578T	Cancer cell line	Female
CVCL_0807	Hs 578Bst	Finite cell line	Female
CVCL_8A60	GM03672	Finite cell line	Female
CVCL_9916	XTC.UC1	Cancer cell line	Female
CVCL_A8WI	KUCFRi003-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01831934	PHASE4	COMPLETED	Responses to Influenza Vaccine in Patients With Mitochondrial Disorders (MELAS)
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
NCT02396732	PHASE4	TERMINATED	Aspirin and Enoxaparin for VTE in Trauma
NCT02412982	PHASE4	COMPLETED	Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
NCT02464969	PHASE4	COMPLETED	Apixaban for the Acute Treatment of Venous Thromboembolism in Children
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02559856	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
NCT02856295	PHASE4	COMPLETED	anti10a Levels in Women Treated With LMWH in the Postpartum Period
NCT02945280	PHASE4	TERMINATED	Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03006562	PHASE4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03158792	PHASE4	COMPLETED	Enoxaparin 20mg Versus 30mg Subcutaneously Once Daily in Elderly Patients With Impaired Renal Function
NCT03196349	PHASE4	TERMINATED	Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT03266783	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism
NCT03426982	PHASE4	UNKNOWN	Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
NCT03678506	PHASE4	TERMINATED	Apixaban for Extended Anticoagulation (APIDULCIS)
NCT03988101	PHASE4	COMPLETED	Role of Statin in Venous Dysfunction in Patients With Venous Thromboembolism Event
NCT03988231	PHASE4	WITHDRAWN	Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
NCT04128254	PHASE4	UNKNOWN	A Prospective Study in Chinese Patients With Lower Extremity Ankle Fracture of Oral Anticoagulants to Prevent Venous Thromboembolism (VTE)
NCT04157881	PHASE4	COMPLETED	A Study on the Impact of Rabeprazole-induced Elevated Stomach pH on APO-Dabigatran Exposure in Healthy Volunteers
NCT04168203	PHASE4	COMPLETED	Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism
NCT04169269	PHASE4	UNKNOWN	Deep Vein Thrombosis Prophylaxis Adherence: Enoxaparin vs Rivaroxaban
NCT04263038	PHASE4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy