MT-CO1

Summary

MT-CO1 (mitochondrially encoded cytochrome c oxidase I, HGNC:7419) is a protein-coding gene on chromosome mitochondria, encoding Cytochrome c oxidase subunit 1 (P00395). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

Contributes to cytochrome-c oxidase activity. Predicted to be involved in aerobic respiration; positive regulation of vasoconstriction; and respiratory electron transport chain. Located in mitochondrial membrane. Part of respiratory chain complex IV.

Source: NCBI Gene 4512 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +5 more curated relationships
• Clinical variants (ClinVar): 245 total — 16 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 146
• Druggable target: yes

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7419
Approved symbol	MT-CO1
Name	mitochondrially encoded cytochrome c oxidase I
Location	mitochondria
Locus type	gene with protein product
Status	Approved
Aliases	COX1, COI
Ensembl gene	ENSG00000198804
Ensembl biotype	protein_coding
OMIM	516030
Entrez	4512

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361624

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000361624 — 1 exons

Exon	Start	End
ENSE00001435647	5904	7445

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2999 / max 796.8091, expressed in 1632 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194866	8.2999	1632

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	100.00	gold quality
stromal cell of endometrium	CL:0002255	100.00	gold quality
rectum	UBERON:0001052	100.00	gold quality
smooth muscle tissue	UBERON:0001135	100.00	gold quality
vermiform appendix	UBERON:0001154	100.00	gold quality
right uterine tube	UBERON:0001302	100.00	gold quality
right coronary artery	UBERON:0001625	100.00	gold quality
apex of heart	UBERON:0002098	100.00	gold quality
gall bladder	UBERON:0002110	100.00	gold quality
duodenum	UBERON:0002114	100.00	gold quality
fallopian tube	UBERON:0003889	100.00	gold quality
mucosa of transverse colon	UBERON:0004991	100.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	100.00	gold quality
right adrenal gland cortex	UBERON:0035827	100.00	gold quality
islet of Langerhans	UBERON:0000006	99.99	gold quality
zone of skin	UBERON:0000014	99.99	gold quality
colonic epithelium	UBERON:0000397	99.99	gold quality
prefrontal cortex	UBERON:0000451	99.99	gold quality
heart	UBERON:0000948	99.99	gold quality
right lobe of liver	UBERON:0001114	99.99	gold quality
right lobe of thyroid gland	UBERON:0001119	99.99	gold quality
transverse colon	UBERON:0001157	99.99	gold quality
fundus of stomach	UBERON:0001160	99.99	gold quality
body of stomach	UBERON:0001161	99.99	gold quality
mucosa of stomach	UBERON:0001199	99.99	gold quality
right adrenal gland	UBERON:0001233	99.99	gold quality
left adrenal gland	UBERON:0001234	99.99	gold quality
endometrium	UBERON:0001295	99.99	gold quality
left uterine tube	UBERON:0001303	99.99	gold quality
muscle of leg	UBERON:0001383	99.99	gold quality

Single-cell (SCXA)

Detected in 85 experiment(s), a significant marker in 43.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	84142.60
E-CURD-98	yes	71862.66
E-MTAB-6308	yes	70690.28
E-MTAB-6701	yes	68718.69
E-CURD-88	yes	67934.65
E-GEOD-139324	yes	54625.81
E-HCAD-1	yes	54223.65
E-MTAB-10885	yes	52895.70
E-MTAB-8271	yes	52275.51
E-MTAB-6505	yes	51574.86
E-MTAB-8322	yes	51111.58
E-MTAB-8207	yes	50212.35
E-HCAD-13	yes	50072.92
E-MTAB-10042	yes	50060.88
E-MTAB-10290	yes	49760.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAM

Literature-anchored findings (GeneRIF, showing 40)

• C6489A missense mutation in the mitochondrial DNA (mtDNA) CO I gene encoding the cytochrome c oxidase (COX) subunit I in a 17-year-old girl with epilepsia partialis continua (PMID:12140182)
• study points to a role for surfeit 1(SURF1) in promoting the association of cytochrome c oxidase II with the cytochrome c oxidase I.cytochrome c oxidase subunit 4.cytochrome c oxidase subunit 5A subassembly (PMID:14607829)
• The expression of COX I subunits (I and III)was studied in blood platelets during aging. (PMID:14759509)
• High percentage of a 24.2 kb duplicated molecule was found in lymphocytes whereas the corresponding deletion dimer dominated in muscle. (PMID:15036329)
• A missense mutation within the mitochondrial cytochrome c oxidase I gene is associated with cancer. (PMID:16671096)
• Respiration dysfunction in cell with a mutation in COX I can be complementated by cell fusion with another cell carrying a mutation in cytochrome b. (PMID:16740593)
• Functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. (PMID:17341490)
• Cox-1 is expressed with a wide variety of levels and up-regulated significantly in endometrial cancer at the mRNA and protein levels, and may have an important role in tumor development in endometrial canceer. (PMID:18204294)
• MT-CO1 has a role in moderate mental retardation and a mild exercise intolerance [case report] (PMID:18484665)
• 3 single nucleotide changes in 528 bp cytochrome oxidase gene fragment from 18 myelodysplastic syndrome patients were confirmed. (PMID:18718066)
• the presence of one or more COI missense variants was not significantly associated with prostate cancer in African Americans (PMID:19267350)
• 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)
• Screening of a Greek deafness population for the A7445G mitochondrial DNA COI mutation. (PMID:20382059)
• Data show that homoplasmic G6709A (MT-CO1) and G14804A (MT-CYB) alterations cause amino acid changes in the highly conserved residues. (PMID:21389643)
• the possible role of m.7445 A>G in susceptibility to aminoglycoside induced-hearing loss (PMID:21621438)
• Both full-length and truncated COX1 proteins physically interact with AFG3L2. (PMID:22252130)
• Abeta 1-42 bound to a peptide comprising the amino-terminal region of cytochrome c oxidase subunit 1 (PMID:22927926)
• Possible association of a novel missense mutation A6375G in the mitochondrial cytochrome C oxidase I gene with asthenospermia in the Tunisian population (PMID:23030649)
• mitochondrial DNA mutations in COI resulting in increased reactive oxygen and reactive nitrogen generation may be involved in prostate cancer biology (PMID:23509693)
• A novel m.6307A>G mutation in the mitochondrial COXI gene in asthenozoospermic infertile men. (PMID:23712756)
• A novel heteroplasmic mutation was identified in MTCO1, m.7402delC, causing frameshift and a premature termination codon in a mitochondrial encephalomyopathy patient with cytochrome c oxidase deficiency. (PMID:24956508)
• studies have provided mechanistic insights into crosstalk between assembly intermediates, import processes and the synthesis of COX subunits in mitochondria, thus linking conceptually separated functions. (PMID:25663696)
• The m.9267G>C MT-COIII mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A. (PMID:25701779)
• patients with primary ovarian insufficiency exhibit an increased incidence of mitochondrial cytochrome c oxidase 1 gene mutations;MT-CO1 gene mutation may be causal in the disease (PMID:26225554)
• High MTCO1 expression is associated with cognitive impairment in lung cancer. (PMID:26987334)
• The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts. (PMID:28247525)
• Differential Expression of Cytochrome C Oxidase Subunit I Along the Colorectal Adenoma: Carcinoma Progression. (PMID:28362707)
• We investigated A5935G, G5949A, G6081A, G6267A mutations in MT-CO1 and T9540C in MT-CO3, and alterations detected during the analysis of MT-CO gene fragments in endometrial hyperplasia. Three new alterations detected in this study (A6052G, A9545G, G9575A) were described for the first time. (PMID:28819937)
• TGFbeta1 reduced complex IV protein MTCO1 abundance in both myoblasts and myotubes. (PMID:29335583)
• The V83I polymorphism was associated strongly with primary open-angle glaucoma (POAG) in African American men and disrupts amyloid beta-peptide binding to CO1. This region also interacts with a neuroprotective protein, UBQLN1. (PMID:29610859)
• We speculated that the mtDNA T6459C(MT-CO1) mutation might be the basis for the genetic susceptibility to sepsis. (PMID:30207067)
• Determined by the COXI variant. (PMID:30334343)
• Adult-onset Leigh syndrome linked to the novel stop codon mutation m.6579G>A in MT-CO1. (PMID:30743023)
• the present study provides novel insights into the functional role of somatic mutations within MT-CO1 promoting cancer phenotype. (PMID:31299394)
• COX-1, COX-2, and CD147 appear to be independently regulated in oral squamous cell carcinoma (OSCC), potentially representing 2 therapeutic targets for future investigation. COX-1 expression in OSCC deserves further study because it may be an important determinant of PGE2 secretion from OSCC cells (PMID:31350224)
• Novel Mutations of mtDNA m.14568G>A/m.14568C>T in MT-ND6 and m.7299A>G in MT-CO1: Evidence of Pathogenicity in Leber Hereditary Optic Neuropathy. (PMID:32358433)
• G6036A substitution in mitochondrial COX I gene compromises cytochrome c oxidase activity in thiamine responsive Leigh syndrome patients. (PMID:32428756)
• Smart Nano-PROTACs Reprogram Tumor Microenvironment for Activatable Photo-metabolic Cancer Immunotherapy. (PMID:34927316)
• Thymidine Kinase 2 and Mitochondrial Protein COX I in the Cerebellum of Patients with Spinocerebellar Ataxia Type 31 Caused by Penta-nucleotide Repeats (TTCCA)n. (PMID:35084690)
• 15-lipoxygenase and cyclooxygenase expression profile and their related modulators in COVID-19 infection. (PMID:37716021)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt-co1	ENSDARG00000063905
mus_musculus	mt-Co1	ENSMUSG00000064351
rattus_norvegicus	Mt-co1	ENSRNOG00000034234
drosophila_melanogaster	mt:CoI	FBGN0013674
caenorhabditis_elegans		WBGENE00010964

Protein

Protein identifiers

Cytochrome c oxidase subunit 1 — P00395 (reviewed: P00395)

Alternative names: Cytochrome c oxidase polypeptide I

All UniProt accessions (2): P00395, U5YWV7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.

Subunit / interactions. Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and COXFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)). As a newly synthesized protein, rapidly incorporates into a multi-subunit assembly intermediate in the inner membrane, called MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, whose core components are COA3/MITRAC12 and COX14. Within the MITRAC complex, interacts with COA3 and with SMIM20/MITRAC7; the interaction with SMIM20 stabilizes the newly synthesized MT-CO1 and prevents its premature turnover. Interacts with TMEM177 in a COX20-dependent manner.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. 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 the gene represented in this entry. MT-CO1 may play a role in the pathogenesis of acquired idiopathic sideroblastic anemia, a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria. Mitochondrial iron overload may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis. Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110] A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. The disease is caused by variants affecting the gene represented in this entry. Recurrent myoglobinuria mitochondrial (RM-MT) [MIM:550500] Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine. The gene represented in this entry may be involved in disease pathogenesis. Deafness, sensorineural, mitochondrial (DFNM) [MIM:500008] A form of non-syndromic deafness with maternal inheritance. Affected individuals manifest progressive, postlingual, sensorineural hearing loss involving high frequencies. The disease is caused by variants affecting the gene represented in this entry. Colorectal cancer (CRC) [MIM:114500] A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. The gene represented in this entry may be involved in disease pathogenesis.

Cofactor. Binds 2 heme A groups non-covalently per subunit. Binds a copper B center.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the heme-copper respiratory oxidase family.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000883	Cyt_C_Oxase_1	Family
IPR023615	Cyt_c_Oxase_su1_BS	Binding_site
IPR023616	Cyt_c_oxase-like_su1_dom	Domain
IPR033944	Cyt_c_oxase_su1_dom	Domain
IPR036927	Cyt_c_oxase-like_su1_sf	Homologous_superfamily

Pfam: PF00115

Enzyme classification (BRENDA):

• EC 7.1.1.9 — cytochrome-c oxidase (BRENDA: 151 organisms, 119 substrates, 144 inhibitors, 123 Km, 118 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FERROCYTOCHROME C	—	86
REDUCED CYTOCHROME C551	—	9
FERROCYTOCHROME C552	0.0022–0.018	7
FERROCYTOCHROME C550	0.003–0.024	3
FERROCYTOCHROME C549	0.0047–0.0065	2
FERROCYTOCHROME C551	0.067	2
O2	—	2
REDUCED ASCORBATE-N,N,N’,N’-TETRAMETHYL-1,4-PHEN	0.23–0.27	2
FERROCYTOCHROME C553	0.0009	1
N,N,N’,N’-TETRAMETHYL-P-PHENYLENEDIAMINE	0.86	1
O-DIANISIDINE	0.09	1
REDUCED ASCORBATE-N,N,N’,N’-TETRAMETHYL-4-PHENYL	2	1
DIAMINODURENE	—	0
N,N,N’,N’-TETRAMETHYL-4-PHENYLENDIAMINE	—	0
PHENAZINE METHOSULFATE	—	0

Catalyzed reactions (Rhea), 1 shown:

• 4 Fe(II)-[cytochrome c] + O2 + 8 H(+)(in) = 4 Fe(III)-[cytochrome c] + 2 H2O + 4 H(+)(out) (RHEA:11436)

UniProt features (52 total): sequence variant 14, topological domain 13, transmembrane region 12, binding site 11, chain 1, cross-link 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9I6F	ELECTRON MICROSCOPY	2.95
9I7U	ELECTRON MICROSCOPY	3.15
5Z62	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00395-F1	95.77	0.92

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 (11): 40; 45; 61 (axial binding residue); 240; 244; 290; 291; 368; 369; 376 (axial binding residue); 378 (axial binding residue)

Post-translational modifications (1): 240–244

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-5419276	Mitochondrial translation termination
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-611105	Respiratory electron transport
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 402 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, TGACCTY_ERR1_Q2, GOBP_RESPONSE_TO_COPPER_ION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_ELECTRON_TRANSPORT_CHAIN, KEGG_HUNTINGTONS_DISEASE, GOCC_MITOCHONDRIAL_ENVELOPE, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, WINTER_HYPOXIA_METAGENE

GO Biological Process (11): response to hypoxia (GO:0001666), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), response to oxidative stress (GO:0006979), aerobic respiration (GO:0009060), cerebellum development (GO:0021549), respiratory electron transport chain (GO:0022904), cellular respiration (GO:0045333), response to copper ion (GO:0046688), response to electrical stimulus (GO:0051602), oxidative phosphorylation (GO:0006119), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): cytochrome-c oxidase activity (GO:0004129), heme binding (GO:0020037), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial membrane (GO:0031966), respiratory chain complex IV (GO:0045277), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Mitochondrial translation	1
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Cellular response to chemical stress	1
Metabolism of proteins	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	2
cellular respiration	2
response to decreased oxygen levels	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
metencephalon development	1
anatomical structure development	1
electron transport chain	1
energy derivation by oxidation of organic compounds	1
response to metal ion	1
response to abiotic stimulus	1
aerobic respiration	1
proton motive force-driven ATP synthesis	1
monoatomic cation transmembrane transport	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on a heme group of donors	1
active monoatomic ion transmembrane transporter activity	1
tetrapyrrole binding	1
cation binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT-CO1	MT-CO2	P00403	999
MT-CO1	MT-CO3	P00414	999
MT-CO1	UQCRC2	P22695	978
MT-CO1	COX4I1	P13073	975
MT-CO1	MT-CYB	P00156	970
MT-CO1	MT-ND5	P03915	967
MT-CO1	MT-ND6	P03923	963
MT-CO1	MT-ND4	P03905	960
MT-CO1	MT-ND2	P03891	958
MT-CO1	MT-ATP6	P00846	947
MT-CO1	MT-ND1	P03886	939
MT-CO1	MT-ND3	P03897	919
MT-CO1	MT-ND4L	P03901	919
MT-CO1	ZNF346	Q9UL40	899
MT-CO1	NDUFB8	O95169	892

IntAct

89 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
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
COA3	MT-CO1	psi-mi:“MI:0914”(association)	0.610
MT-CO1	COA3	psi-mi:“MI:0915”(physical association)	0.610
COA3	MT-CO1	psi-mi:“MI:0915”(physical association)	0.610
COX4I1	MT-CO1	psi-mi:“MI:0915”(physical association)	0.560
MT-CO1	COX4I1	psi-mi:“MI:0915”(physical association)	0.560
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
GPR141	STXBP3	psi-mi:“MI:0914”(association)	0.530
COX5A	COX7A2L	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
ASGR2	MT-CO1	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
TIMM21	TIMM23	psi-mi:“MI:0914”(association)	0.500
MT-CO1	APP	psi-mi:“MI:0407”(direct interaction)	0.440
HSPB2	MT-CO1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (84): COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Two-hybrid), COX1 (Affinity Capture-Western), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX1 (Affinity Capture-MS)

ESM2 similar proteins: A9RAH5, O03198, O21327, O78749, O79403, O79429, O79548, O79876, O99041, P00395, P00396, P00397, P00398, P05503, P24983, P33504, P38595, P41293, P48659, P48887, P48888, P92477, Q00527, Q1HKA1, Q2I3H2, Q34800, Q36347, Q36724, Q37705, Q38PS0, Q599A1, Q5Y4Q8, Q6EGH7, Q6EGH8, Q6EGH9, Q6EGI0, Q6EGI3, Q6EGI5, Q6EGJ0, Q6EGJ1

Diamond homologs: B0FWC7, O03167, O03198, O21079, O21327, O21399, O78681, O78749, O79403, O79429, O79548, O79672, O79876, O99041, O99818, P00395, P00396, P00397, P00398, P00399, P00400, P05503, P12700, P15544, P18943, P20374, P24794, P24983, P24984, P24985, P25001, P26856, P33504, P34188, P34838, P38595, P41293, P41310, P48170, P48659

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
chloramphenicol	“down-regulates quantity”	MT-CO1	“chemical inhibition”
MT-CO1	“form complex”	“Cytochrome c oxidase-Mitochondrial respiratory chain complex IV”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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 IV assembly	15	52.7×	2e-20
Cytoprotection by HMOX1	9	25.5×	4e-09
TP53 Regulates Metabolic Genes	10	20.0×	4e-09
Respiratory electron transport	13	19.0×	1e-11
Mitochondrial protein degradation	7	12.3×	7e-05
Peptide ligand-binding receptors	8	9.1×	9e-05
G alpha (q) signalling events	9	8.0×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, cytochrome c to oxygen	10	92.3×	2e-15
cellular respiration	8	41.6×	5e-09
mitochondrial respiratory chain complex IV assembly	5	37.6×	4e-05
generation of precursor metabolites and energy	8	33.1×	3e-08
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	15.8×	3e-04
phospholipase C-activating G protein-coupled receptor signaling pathway	8	12.7×	4e-05
G protein-coupled receptor signaling pathway	12	5.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	7
Uncertain significance	110
Likely benign	40
Benign	58

Top pathogenic / likely-pathogenic (23)

Variant ID	HGVS	Classification
587690	NC_012920.1(MT-CO1):m.6941del	Pathogenic
590294	NC_012920.1(MT-CO1):m.6902del	Pathogenic
590295	NC_012920.1(MT-CO1):m.6927del	Pathogenic
590296	NC_012920.1(MT-CO1):m.6936del	Pathogenic
590297	NC_012920.1(MT-CO1):m.6860del	Pathogenic
590890	NC_012920.1(MT-CO1):m.6817del	Pathogenic
590893	NC_012920.1(MT-CO1):m.5954del	Pathogenic
590946	NC_012920.1(MT-CO1):m.6608del	Pathogenic
590948	NC_012920.1(MT-CO1):m.6698del	Pathogenic
590996	NC_012920.1(MT-CO1):m.6688_6689insACC	Pathogenic
590999	NC_012920.1(MT-CO1):m.6743_6744insTGG	Pathogenic
599214	NC_012920.1(MT-CO1):m.6718_6719insGGG	Pathogenic
599215	NC_012920.1(MT-CO1):m.6750del	Pathogenic
9563	NC_012920.1(MT-TS1):m.7445A>G	Pathogenic
9672	NC_012920.1(MT-CO1):m.6277G>A	Pathogenic
9673	NC_012920.1(MT-CO1):m.7275T>C	Pathogenic
209212	NC_012920.1(MT-TY):m.5782_13922del	Likely pathogenic
590895	NC_012920.1(MT-CO1):m.6809_6810insAAG	Likely pathogenic
590897	NC_012920.1(MT-CO1):m.6907_6908insCTC	Likely pathogenic
590898	NC_012920.1(MT-CO1):m.6889_6890insGGG	Likely pathogenic
590947	NC_012920.1(MT-CO1):m.6674del	Likely pathogenic
9668	NC_012920.1(MT-CO1):m.6930G>A	Likely pathogenic
9669	NC_012920.1(MT-CO1):m.5920G>A	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
M:6654:T:C	F251L	1.000
M:6656:C:A	F251L	1.000
M:6656:C:G	F251L	1.000
M:6753:G:C	G284R	1.000
M:6771:C:G	H290D	1.000
M:6838:T:A	I312N	1.000
M:6841:C:A	A313D	1.000
M:6847:C:A	P315H	1.000
M:6852:G:C	G317R	1.000
M:6853:G:A	G317D	1.000
M:6864:T:C	F321L	1.000
M:6866:T:A	F321L	1.000
M:6866:T:G	F321L	1.000
M:6870:T:C	W323R	1.000
M:6945:T:C	F348L	1.000
M:6947:C:A	F348L	1.000
M:6947:C:G	F348L	1.000
M:7053:G:T	G384W	1.000
M:5942:A:C	K13N	0.999
M:5942:A:T	K13N	0.999
M:5949:G:C	G16R	0.999
M:5949:G:T	G16W	0.999
M:5950:G:A	G16E	0.999
M:6118:C:A	P72H	0.999
M:6138:G:C	G79R	0.999
M:6139:G:A	G79D	0.999
M:6143:C:A	N80K	0.999
M:6143:C:G	N80K	0.999
M:6197:C:A	N98K	0.999
M:6197:C:G	N98K	0.999

dbSNP variants (sampled 300 via entrez): RS1029272 (MT:6185 T>C), RS1029293 (MT:6308 C>T), RS1029294 (MT:6473 C>T), RS1041840 (MT:6383 G>A), RS1041870 (MT:6151 T>C), RS1057516059 (MT:4664 C>T), RS1057516060 (MT:7373 A>G), RS1057516061 (MT:7496 T>C), RS1057520057 (MT:5105 T>C), RS1057520067 (MT:4472 T>C), RS1057520195 (MT:6299 A>G), RS1057520201 (MT:4132 G>A), RS111033173 (MT:7468 C>A,T), RS111033319 (MT:7465 AC>A,ACC), RS111033324 (MT:7498 G>A)

Disease associations

OMIM: gene MIM:516030 | disease phenotypes: MIM:540000, MIM:256000, MIM:500013, MIM:500018, MIM:500008, MIM:187500, MIM:500009, MIM:148350, MIM:535000, MIM:580000, MIM:220110, MIM:550500

GenCC curated gene-disease

Disease	Classification	Inheritance
cytochrome-c oxidase deficiency disease	Supportive	Autosomal recessive
MELAS syndrome	Supportive	Mitochondrial
mitochondrial non-syndromic sensorineural hearing loss	Supportive	Mitochondrial
hereditary recurrent myoglobinuria	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Leigh syndrome	Limited	MT
mitochondrial disease	Definitive	MT

Mondo (20): mitochondrial disease (MONDO:0044970), MELAS syndrome (MONDO:0010789), dilated cardiomyopathy (MONDO:0005021), Leigh syndrome (MONDO:0009723), epilepsy (MONDO:0005027), Charcot-Marie-Tooth disease, axonal, mitochondrial form, 1 (MONDO:0025622), spastic paraplegia, mitochondrial (MONDO:0975951), optic atrophy (MONDO:0003608), mitochondrial non-syndromic sensorineural hearing loss (MONDO:0010779), tetralogy of fallot (MONDO:0008542), mitochondrial myopathy with reversible cytochrome C oxidase deficiency (MONDO:0010780), palmoplantar keratoderma-deafness syndrome (MONDO:0007852), Leber hereditary optic neuropathy (MONDO:0010788), deafness, aminoglycoside-induced (MONDO:0010799), myelodysplastic syndrome with ring sideroblasts (MONDO:0019157)

Orphanet (12): Mitochondrial disease (Orphanet:68380), MELAS (Orphanet:550), Dilated cardiomyopathy (Orphanet:217604), Leigh syndrome (Orphanet:506), Rare mitochondrial non-syndromic sensorineural deafness (Orphanet:90641), Tetralogy of Fallot (Orphanet:3303), Mitochondrial myopathy with reversible cytochrome C oxidase deficiency (Orphanet:254864), Palmoplantar keratoderma-deafness syndrome (Orphanet:2202), Leber hereditary optic neuropathy (Orphanet:104), Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure (Orphanet:168609), Acquired idiopathic sideroblastic anemia (Orphanet:75564), Genetic recurrent myoglobinuria (Orphanet:99845)

HPO phenotypes

146 total (30 of 146 shown, HPO-id order):

HPO	Term
HP:0000044	Hypogonadotropic hypogonadism
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000112	Nephropathy
HP:0000114	Proximal tubulopathy
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000512	Abnormal electroretinogram
HP:0000519	Developmental cataract
HP:0000529	Progressive visual loss
HP:0000551	Color vision defect
HP:0000572	Visual loss
HP:0000576	Centrocecal scotoma
HP:0000580	Pigmentary retinopathy
HP:0000590	Progressive external ophthalmoplegia
HP:0000602	Ophthalmoplegia
HP:0000603	Central scotoma
HP:0000622	Blurred vision
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism

GWAS associations

0 associations (top):

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D004827	Epilepsy	C10.228.140.490
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
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
C564013	Deafness, Aminoglycoside-Induced (supp.)
C564018	Myoglobinuria, Recurrent (supp.)
C536152	Palmoplantar Keratoderma with Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6173 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

25 measured of 29 human assays (29 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[[(5S)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	5000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclobutanecarboxamide	IC50	5000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3,5-difluoro-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	6000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarboxamide	IC50	8000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarboxamide	IC50	8000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5R)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one	IC50	9000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclobutanecarboxamide	IC50	10000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3,5-difluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclobutanecarboxamide	IC50	13000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]butanamide	IC50	13000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
methyl N-[[(5S)-3-[3,5-difluoro-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]carbamate	IC50	13000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	13600 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5R)-3-[3,5-difluoro-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one	IC50	15000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-thia-6-azabicyclo[3.1.1]heptan-6-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	15200 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5R)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one	IC50	17000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
methyl N-[[(5S)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]carbamate	IC50	19000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5S)-5-(aminomethyl)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-1,3-oxazolidin-2-one	IC50	20000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3,5-difluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	25000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]butanamide	IC50	41000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
methyl N-[[(5S)-3-[3,5-difluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]carbamate	IC50	42500 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5R)-3-[3,5-difluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one	IC50	42500 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
methyl N-[[(5S)-3-[3,5-difluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]carbamate	IC50	51000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5R)-3-[3-fluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one	IC50	57000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
methyl N-[[(5S)-3-[3-fluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]carbamate	IC50	73000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
(5S)-5-(aminomethyl)-3-[3-fluoro-4-(3-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-1,3-oxazolidin-2-one	IC50	77000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy
N-[[(5S)-3-[3-fluoro-4-(3-oxo-3lambda4-thia-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide	IC50	78000 nM	US-11964949: Substituted phenyloxazolidinones for antimicrobial therapy

ChEMBL bioactivities

12 potent at pChembl≥5 of 12 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	IC50	130	nM	CHEMBL1774043
6.62	IC50	240	nM	CHEMBL1773877
6.55	IC50	280	nM	LOXOPROFEN TRANS ALCOHOL
6.49	IC50	321	nM	CHEMBL5568511
6.30	IC50	500	nM	LOXOPROFEN TRANS ALCOHOL
5.89	IC50	1286	nM	CHEMBL5568474
5.87	IC50	1358	nM	CHEMBL5568253
5.87	IC50	1364	nM	DUP-697
5.83	IC50	1470	nM	LOXOPROFEN TRANS ALCOHOL
5.54	IC50	2900	nM	CHEMBL5570209
5.51	IC50	3100	nM	CHEMBL5590309
5.24	IC50	5734	nM	CHEMBL5565096

PubChem BioAssay actives

12 with measured affinity, of 50 total; 10 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
3-[4-[4-(2-fluoro-4-methylphenyl)-5-(4-methoxyphenyl)pyrimidine-2-carbonyl]piperazin-1-yl]naphthalene-1-carboxylic acid	595918: Inhibition of COX1	ic50	0.1300	uM
3-[4-[5-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-(2-fluoro-4-methylphenyl)pyrimidine-2-carbonyl]piperazin-1-yl]naphthalene-1-carboxylic acid	595918: Inhibition of COX1	ic50	0.2400	uM
(2S)-2-[4-[[(1R,2S)-2-hydroxycyclopentyl]methyl]phenyl]propanoic acid	1906166: Inhibition of COX-1 in human whole blood assessed as reduction in thromboxane B2 production by immunoassay	ic50	0.2800	uM
4-[(5-ethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]-N-hydroxybenzamide	2067622: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins by fluorescence based analysis	ic50	0.3210	uM
4-[(5-tert-butyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]-N-hydroxybenzamide	2067622: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins by fluorescence based analysis	ic50	1.2860	uM
4-[[2-(3-chlorophenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]methyl]-N-hydroxybenzamide	2067622: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins by fluorescence based analysis	ic50	1.3580	uM
5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene	2067622: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins by fluorescence based analysis	ic50	1.3640	uM
5,6-difluoro-1-methyl-N-[(E)-1-pyrimidin-2-ylethylideneamino]benzimidazol-2-amine	2103480: Inhibition of COX1 (unknown origin)	ic50	2.9000	uM
5,6-difluoro-N-[(E)-1-(5-fluoro-2-pyridinyl)ethylideneamino]-1-methylbenzimidazol-2-amine	2103480: Inhibition of COX1 (unknown origin)	ic50	3.1000	uM
N-hydroxy-4-[(5-methyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]benzamide	2067622: Inhibition of COX-1 (unknown origin) using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins by fluorescence based analysis	ic50	5.7340	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
enniatins	affects expression, decreases expression, affects cotreatment	4
Valproic Acid	increases expression, decreases expression, decreases methylation	4
Air Pollutants	increases abundance, decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
1-Methyl-4-phenylpyridinium	decreases reaction, decreases expression, increases reaction	3
beauvericin	affects cotreatment, affects expression, decreases expression	2
bisphenol A	decreases expression, increases expression	2
Resveratrol	affects reaction, increases expression	2
Atrazine	affects expression, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Plant Extracts	increases expression, affects cotreatment, decreases expression	2
Dronabinol	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	increases expression	1
di-n-octyl phthalate	affects expression	1
kojic acid	increases expression	1
tetrabromobisphenol A	increases expression	1
fucoxanthin	increases expression, decreases reaction	1
ochratoxin A	affects cotreatment, decreases expression	1
acipimox	increases expression	1
aflatoxin G1	affects cotreatment, decreases expression	1
aflatoxin B2	affects cotreatment, decreases expression	1
aflatoxin G2	affects cotreatment, decreases expression	1
tris(chloroethyl)phosphate	increases abundance, increases expression	1
hydroquinone	increases expression	1
puerarin	increases expression	1
dimethoxyethyl phthalate	decreases expression	1
diallyl trisulfide	decreases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 12 binding, 4 functional, 2 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1775456	Binding	Inhibition of COX1	Discovery of pyrimidine carboxamides as potent and selective CCK1 receptor agonists. — Bioorg Med Chem Lett
CHEMBL4181303	ADMET	Inhibition of COX1 in human U937 cells at 10 uM using arachidonic acid as substrate pretreated for 15 mins followed by substrate addition measured after 5 mins relative to control	Discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1. — Bioorg Med Chem Lett
CHEMBL4739597	Functional	Inhibition of mitochondrial COX1 expression in human GFP-labelled MDA-MB-231 cells at 1 uM incubated for 72 hrs under low oxygen condition by Western blot analysis	Impact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells. — ACS Med Chem Lett

Clinical trials (associated diseases)

185 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)
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00068913	PHASE2	UNKNOWN	Evaluating the Effectiveness of a Dichloroacetate in MELAS Syndrome
NCT00887562	PHASE2	COMPLETED	Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
NCT01603446	PHASE2	COMPLETED	L-arginine Therapy on Endothelium-dependent Vasodilation & Mitochondrial Metabolism in MELAS Syndrome
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04475549	PHASE2	TERMINATED	Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT06644534	PHASE2	RECRUITING	A Study to Assess TTI-0102 vs Placebo in MELAS Patients
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)