MT-CO2

Summary

MT-CO2 (mitochondrially encoded cytochrome c oxidase II, HGNC:7421) is a protein-coding gene on chromosome mitochondria, encoding Cytochrome c oxidase subunit 2 (P00403). 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 mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington’s disease and stomach cancer.

Source: NCBI Gene 4513 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 131 total — 6 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 103
• Druggable target: yes — 6 molecules with ChEMBL bioactivity

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7421
Approved symbol	MT-CO2
Name	mitochondrially encoded cytochrome c oxidase II
Location	mitochondria
Locus type	gene with protein product
Status	Approved
Aliases	COX2, CO2
Ensembl gene	ENSG00000198712
Ensembl biotype	protein_coding
OMIM	516040
Entrez	4513

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361739

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000361739 — 1 exons

Exon	Start	End
ENSE00001435613	7586	8269

Expression profiles

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

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3081 / max 922.6606, expressed in 1600 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194880	8.3081	1600
194881	4.0535	1240

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
rectum	UBERON:0001052	100.00	gold quality
transverse colon	UBERON:0001157	100.00	gold quality
mucosa of stomach	UBERON:0001199	100.00	gold quality
right adrenal gland	UBERON:0001233	100.00	gold quality
left adrenal gland	UBERON:0001234	100.00	gold quality
right uterine tube	UBERON:0001302	100.00	gold quality
left uterine tube	UBERON:0001303	100.00	gold quality
skin of abdomen	UBERON:0001416	100.00	gold quality
frontal cortex	UBERON:0001870	100.00	gold quality
temporal lobe	UBERON:0001871	100.00	gold quality
caudate nucleus	UBERON:0001873	100.00	gold quality
putamen	UBERON:0001874	100.00	gold quality
amygdala	UBERON:0001876	100.00	gold quality
nucleus accumbens	UBERON:0001882	100.00	gold quality
hypothalamus	UBERON:0001898	100.00	gold quality
Ammon’s horn	UBERON:0001954	100.00	gold quality
cerebellum	UBERON:0002037	100.00	gold quality
substantia nigra	UBERON:0002038	100.00	gold quality
heart left ventricle	UBERON:0002084	100.00	gold quality
small intestine	UBERON:0002108	100.00	gold quality
cerebellar cortex	UBERON:0002129	100.00	gold quality
right lung	UBERON:0002167	100.00	gold quality
cerebellar hemisphere	UBERON:0002245	100.00	gold quality
right frontal lobe	UBERON:0002810	100.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	100.00	gold quality
mucosa of transverse colon	UBERON:0004991	100.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	100.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	100.00	gold quality
anterior cingulate cortex	UBERON:0009835	100.00	gold quality

Single-cell (SCXA)

Detected in 82 experiment(s), a significant marker in 39.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	70635.75
E-CURD-88	yes	57991.51
E-MTAB-6505	yes	44478.77
E-HCAD-13	yes	44244.44
E-CURD-55	yes	44116.93
E-MTAB-8271	yes	40158.57
E-CURD-77	yes	38649.13
E-MTAB-9435	yes	38034.65
E-MTAB-6701	yes	37770.34
E-MTAB-6308	yes	34346.84
E-HCAD-1	yes	33320.18
E-HCAD-6	yes	32598.53
E-HCAD-5	yes	30386.79
E-MTAB-10885	yes	29174.74
E-GEOD-139324	yes	28211.44

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 37)

• Ageing muscle: clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function. (PMID:12031622)
• the expression of mitochondria-encoded COXII is HRG-responsive. The levels of ErbB2 expression are decisive for the diverse biological activities of HRG. (PMID:12115729)
• 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)
• frequency of occurrence of mtDNA with the COII/tRNA(Lys) intergenic 9-bp deletion polymorphism in patients with myoclonic epilepsy with ragged-red fibers or mitochondrial encephalomyopathy syndrome is higher than that of healthy subjects (PMID:15965049)
• Mutations in mtDNA-encoded cytochrome c oxidase subunit II genes causing isolated myopathy or severe encephalomyopathy. (PMID:16288875)
• DNA hypermethylation of the COX-2 gene may be a potential prognostic marker in early stage cervical cancer. (PMID:17578348)
• mitochondrial 12S/MT-RNR1, MT-CO2/COX2, and MT-ATP6 transcripts is significantly decreased in prostate tumor samples (PMID:18409190)
• a fraction of Sco1 physically associates with the cytochrome c oxidase complex in human muscle mitochondria, suggesting a possible direct relationship between CcO and the regulation of cellular copper homeostasis (PMID:19295170)
• SCO2 acts upstream of SCO1, and that it is indispensable for CO II synthesis. (PMID:19336478)
• COX-II is induced in HIV infected apoptotic T-cells. (PMID:19771519)
• CoxII can be phosphorylated by EGFR and c-Src, and EGF stimulation reduces Cox activity and cellular ATP, an event that is dependent in large part on EGFR localized to the mitochondria. (PMID:19840943)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• COX-2 expression played an essential role in the proliferation and metastasis of tongue cancer. (PMID:21069476)
• The apoptotic index of pulmonary vascular endothelial cells was negatively correlated with COXII expression in patients with chronic obstructive pulmonary disease. (PMID:21092633)
• Novel COII mutations responsible for maternally inherited nonsyndromic hearing loss (PMID:22241583)
• The presence of a non-synonymous variation in the COII strongly correlated with poor survival in patients with cytogenetically normal acute myeloid leukemia. (PMID:23826975)
• Mutational analysis show a novel MTCO2 mutation 8249G>A pathogenic variation in Tunisian patients with mitochondrial myopathy. (PMID:23841600)
• Protein modeling revealed loss of function mutations of ND6 and COX-II proteins in malignant vs benign tumors (PMID:24061460)
• We also detected in 4 asthenospermic patients a double novels mutations, the first was found in COXII gene (m.8021 G/A) that was absent in normospermic infertile men. (PMID:24931671)
• The sequencing analysis revealed the presence of 17 variants, mostly causing non-synonymous changes in conserved amino acid residues, typically distributed in the MT-CO2 gene of MUTYH-associated polyposis patients (P < 0.0001), who frequently carried the hot spot m.7763G>A variant. (PMID:26138249)
• Results find that COA6 associates with COX2 and is crucial for its maturation and complex IV biogenesis. Also, COA6 interacts with the copper chaperone SCO1 which indicates that COA6 is intrinsically involved in the copper delivery process for COX2. (PMID:26160915)
• inhibitory effects of 17-AAG on PGE2 levels in HT-29 colorectal cancer cells were mediated through modulating COX-2 and 15-PGDH expression. (PMID:27075590)
• Data suggest that mutations in MT-CO2 and MT-ND5 can be involved in MIDD (maternally inherited diabetes and deafness); a Tunisian family (mother, daughter, son) with clinical features of MIDD associated with retinopathy exhibit mutations in MT-CO2 (m.8241T>G - p. F219C) and MT-ND5 (m.13276G>A - p. M314V); these two mutations could explain retinopathy in some family members. (MT-ND5 = NADH dehydrogenase subunit 5) (PMID:27422531)
• Results demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis. [metastasis] (PMID:27999206)
• Study shows that higher COX-2 and ALOX5 expression in colorectal cancer (CRC) tissues was correlated with poorer prognosis in patients with CRC. Also, MiR-216a-3p was shown to directly bind to there 3’-UTR and inversely regulates their protein levels modulating CRC cell proliferation. (PMID:28786533)
• results demonstrated that XRCC5 promoted colon cancer growth by cooperating with p300 to regulate COX-2 expression, and suggested that the XRCC5/p300/COX-2 signaling pathway was a potential target in the treatment of colon cancers (PMID:29049411)
• Studied Cyclooxygenase-2 (COX-2) gene polymorphisms in a Turkish population with thyroid cancer; found the COX-2-8473T>C gene polymorphism may cause genetic susceptibility to thyroid cancer as compared to the control group. (PMID:29306248)
• MT-CO2 mutation m.8088delT resulting in a premature stop codon was identified in a patient with myopathy and perturbed acylcarnitine profile. (PMID:30315213)
• 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)
• Mitochondrial miR-181a-5p promotes glucose metabolism reprogramming in liver cancer by regulating the electron transport chain. (PMID:31628462)
• Novel Point Mutations in Mitochondrial MT-CO2 Gene May Be Risk Factors for Coronary Artery Disease. (PMID:32096057)
• Mitochondrial gene COX2 methylation and downregulation is a biomarker of aging in heart mesenchymal stem cells. (PMID:33416107)
• Immunohistochemical Study and Clinicopathologic Correlation of Cox-2 and Her-2 Expression in Colorectal Carcinoma: A 5-Year Retrospective Study. (PMID:36453435)
• Interferon-gamma is quintessential for NOS2 and COX2 expression in ER[-] breast tumors that lead to poor outcome. (PMID:37169743)
• Helicobacter pylori vacA affects the expression of COX-2 in the duodenal mucosa of patients with duodenitis. (PMID:37382210)
• Elevated expression levels of COX-2, IL-8 and VEGF in colon adenocarcinoma. (PMID:37605577)
• 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-co2	ENSDARG00000063908
mus_musculus	mt-Co2	ENSMUSG00000064354
rattus_norvegicus	Mt-co2	ENSRNOG00000030371
drosophila_melanogaster	mt:CoII	FBGN0013675
caenorhabditis_elegans		WBGENE00010965

Protein

Protein identifiers

Cytochrome c oxidase subunit 2 — P00403 (reviewed: P00403)

Alternative names: Cytochrome c oxidase polypeptide II

All UniProt accessions (2): P00403, U5Z487

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)). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16. Interacts with assembly factor COX11; during cytochrome c oxidase assembly.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. 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.

Cofactor. Binds a dinuclear copper A center per subunit.

Similarity. Belongs to the cytochrome c oxidase subunit 2 family.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001505	Copper_CuA	Binding_site
IPR002429	CcO_II-like_C	Domain
IPR008972	Cupredoxin	Homologous_superfamily
IPR011759	Cyt_c_oxidase_su2_TM_dom	Domain
IPR014222	Cyt_c_oxidase_su2	Domain
IPR034210	CcO_II_C	Domain
IPR036257	Cyt_c_oxidase_su2_TM_sf	Homologous_superfamily
IPR045187	CcO_II	Family

Pfam: PF00116, PF02790

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 (22 total): binding site 9, sequence variant 7, topological domain 3, transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3VRJ	X-RAY DIFFRACTION	1.9
9I6F	ELECTRON MICROSCOPY	2.95
9I7U	ELECTRON MICROSCOPY	3.15
5Z62	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00403-F1	94.82	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 (9): 198; 200; 200; 204; 207; 161; 196; 196; 198

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: 295 (showing top): GOBP_RESPONSE_TO_ETHANOL, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_ELECTRON_TRANSPORT_CHAIN, KEGG_HUNTINGTONS_DISEASE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_MAMMARY_GLAND_DEVELOPMENT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, WINTER_HYPOXIA_METAGENE, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_BODY_FLUID_SECRETION

GO Biological Process (8): response to hypoxia (GO:0001666), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), lactation (GO:0007595), ATP synthesis coupled electron transport (GO:0042773), cellular respiration (GO:0045333), response to ethanol (GO:0045471), electron transport chain (GO:0022900), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): cytochrome-c oxidase activity (GO:0004129), copper ion binding (GO:0005507), oxidoreductase activity (GO:0016491), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020), mitochondrial membrane (GO:0031966), respiratory chain complex IV (GO:0045277)

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
mitochondrion	2
response to stress	1
response to decreased oxygen levels	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
oxidative phosphorylation	1
respiratory electron transport chain	1
energy derivation by oxidation of organic compounds	1
response to alcohol	1
generation of precursor metabolites and energy	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
transition metal ion binding	1
catalytic activity	1
binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
cellular anatomical structure	1
mitochondrial envelope	1
organelle membrane	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

2660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT-CO2	MT-CO1	P00395	999
MT-CO2	MT-CO3	P00414	999
MT-CO2	MT-CYB	P00156	949
MT-CO2	MT-ND4	P03905	949
MT-CO2	MT-ND6	P03923	945
MT-CO2	MT-ND5	P03915	945
MT-CO2	MT-ND2	P03891	944
MT-CO2	CYCS	P00001	942
MT-CO2	COX18	Q8N8Q8	933
MT-CO2	SCO1	O75880	925
MT-CO2	MT-ATP6	P00846	920
MT-CO2	MT-ND3	P03897	919
MT-CO2	MT-ND4L	P03901	915
MT-CO2	MT-ATP8	P03928	913
MT-CO2	COX4I1	P13073	901

IntAct

125 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MT-CO2	COX6C	psi-mi:“MI:0915”(physical association)	0.560
MT-CO2	NLGN3	psi-mi:“MI:0915”(physical association)	0.540
NLGN3	MT-CO2	psi-mi:“MI:0403”(colocalization)	0.540
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530
SLC11A2	MT-CO2	psi-mi:“MI:0915”(physical association)	0.510
PDK1	MT-CO2	psi-mi:“MI:0403”(colocalization)	0.460
PDK1	MT-CO2	psi-mi:“MI:0915”(physical association)	0.460
NLGN3	MT-CO2	psi-mi:“MI:0914”(association)	0.430
NLGN3	MT-CO2	psi-mi:“MI:0403”(colocalization)	0.430
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
SLC11A2	MT-CO2	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	MT-CO2	psi-mi:“MI:0915”(physical association)	0.370
HTRA1	MT-CO2	psi-mi:“MI:0915”(physical association)	0.370
rep	MT-CO2	psi-mi:“MI:0915”(physical association)	0.370
MT-CO2	E6	psi-mi:“MI:0915”(physical association)	0.370
MT-CO2	E7	psi-mi:“MI:0915”(physical association)	0.370
MT-CO2	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
PSMA1	MT-CO2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (272): BCAP31 (Co-fractionation), COX2 (Affinity Capture-MS), COX2 (Affinity Capture-MS), COX2 (Affinity Capture-MS), COX2 (Affinity Capture-Western), COX4I1 (Co-fractionation), DDOST (Co-fractionation), MAGT1 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation), COX2 (Co-fractionation)

ESM2 similar proteins: A6H4Q5, A9RAG1, O47428, O47496, O79417, O79549, P00403, P00410, P00411, P00412, P00413, P06029, P13588, P20387, P20682, P21534, P24894, P26456, P26457, P26857, P29163, P43369, P43370, P43372, P43373, P43374, P43375, P43376, P43377, P47918, P48869, P48870, P48871, P48889, P50690, Q00227, Q01556, Q02212, Q09334, Q0H8Y7

Diamond homologs: O03851, O47667, O47668, O47669, O47671, O47672, O47673, O47674, O47678, O47679, O47680, O47681, O48267, O48276, P00403, P00405, P00406, P11948, P24986, P25312, P26455, P26456, P26457, P38596, P41294, P48660, P48890, P50662, P50667, P50673, P50675, P50678, P50679, P50680, P50690, P50691, P67780, P67781, P67782, P68294

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“Non-structural protein 10”	“down-regulates activity”	MT-CO2	binding
MT-CO2	“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 124 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	9	25.7×	3e-08
Cytoprotection by HMOX1	6	13.8×	8e-04
Defective CFTR causes cystic fibrosis	5	13.7×	3e-03
TP53 Regulates Metabolic Genes	8	13.0×	5e-05
Respiratory electron transport	7	8.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, cytochrome c to oxygen	6	44.6×	3e-06
generation of precursor metabolites and energy	6	20.0×	2e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	57
Likely benign	28
Benign	29

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
430677	NC_012920.1(MT-TR):m.7731_11256del	Pathogenic
587691	NC_012920.1(MT-CO2):m.7639del	Pathogenic
590997	NC_012920.1(MT-CO2):m.7680_7681insGTC	Pathogenic
599024	NC_012920.1(MT-CO2):m.7790_7791insTCC	Pathogenic
599025	NC_012920.1(MT-CO2):m.7815_7817dup	Pathogenic
9662	NC_012920.1(MT-CO2):m.7896G>A	Pathogenic
1710006	NC_012920.1(MT-CO2):m.8156del	Likely pathogenic
488349	NC_012920.1(MT-CO2):m.8088del	Likely pathogenic
590892	NC_012920.1(MT-CO2):m.7661_7662insCCA	Likely pathogenic
590896	NC_012920.1(MT-CO2):m.7669_7670insCAC	Likely pathogenic
9658	NC_012920.1(MT-CO2):m.7587T>C	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
M:8052:C:G	S156W	0.999
M:8072:T:C	W163R	0.999
M:7778:T:C	W65R	0.998
M:7895:T:C	W104R	0.998
M:7901:T:C	W106R	0.998
M:8173:C:A	C196W	0.998
M:8173:C:G	C196W	0.998
M:8184:G:A	C200Y	0.998
M:7897:G:C	W104C	0.997
M:7897:G:T	W104C	0.997
M:8057:G:C	D158H	0.997
M:8066:C:G	H161D	0.997
M:8070:C:G	S162W	0.997
M:8166:G:A	G194D	0.997
M:8171:T:C	C196R	0.997
M:8172:G:A	C196Y	0.997
M:7791:C:A	P69H	0.996
M:7791:C:G	P69R	0.996
M:7887:G:A	G101D	0.996
M:7903:A:C	W106C	0.996
M:7903:A:T	W106C	0.996
M:8037:G:C	R151P	0.996
M:8069:T:C	S162P	0.996
M:8098:A:C	K171N	0.996
M:8098:A:T	K171N	0.996
M:8105:G:C	A174P	0.996
M:8106:C:A	A174E	0.996
M:8118:G:C	R178P	0.996
M:8183:T:C	C200R	0.996
M:8185:T:A	C200W	0.996

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), RS1057516060 (MT:7373 A>G), RS1057516061 (MT:7496 T>C), RS1057516062 (MT:8418 T>C), RS1057518824 (MT:8084 A>G,T), RS1057520115 (MT:8260 T>C), RS1057520195 (MT:6299 A>G), RS1064597 (MT:8647 C>G), RS111033173 (MT:7468 C>A,T), RS111033319 (MT:7465 AC>A,ACC), RS111033324 (MT:7498 G>A)

Disease associations

OMIM: gene MIM:516040 | disease phenotypes: MIM:500009, MIM:256000, MIM:220110, MIM:187500

GenCC curated gene-disease

Disease	Classification	Inheritance
cytochrome-c oxidase deficiency disease	Supportive	Autosomal recessive
MELAS syndrome	Supportive	Mitochondrial

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 (10): mitochondrial myopathy with reversible cytochrome C oxidase deficiency (MONDO:0010780), Leigh syndrome (MONDO:0009723), ischemic stroke (MONDO:1060198), epilepsy (MONDO:0005027), mitochondrial disease (MONDO:0044970), mitochondrial complex IV deficiency, nuclear type 1 (MONDO:0700250), tetralogy of fallot (MONDO:0008542), familial colorectal cancer (MONDO:0023113), (MONDO:0009068), MELAS syndrome (MONDO:0010789)

Orphanet (4): Mitochondrial myopathy with reversible cytochrome C oxidase deficiency (Orphanet:254864), Leigh syndrome (Orphanet:506), Mitochondrial disease (Orphanet:68380), Tetralogy of Fallot (Orphanet:3303)

HPO phenotypes

103 total (30 of 103 shown, HPO-id order):

HPO	Term
HP:0000044	Hypogonadotropic hypogonadism
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:0000519	Developmental cataract
HP:0000572	Visual loss
HP:0000580	Pigmentary retinopathy
HP:0000590	Progressive external ophthalmoplegia
HP:0000602	Ophthalmoplegia
HP:0000648	Optic atrophy
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
HP:0000822	Hypertension
HP:0000829	Hypoparathyroidism
HP:0000998	Hypertrichosis
HP:0001045	Vitiligo
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001269	Hemiparesis
HP:0001270	Motor delay

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
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
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6174 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 523,231 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL118	CELECOXIB	4	112,844
CHEMBL122	ROFECOXIB	4	66,907
CHEMBL139	DICLOFENAC	4	125,009
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL865	VALDECOXIB	4	41,681
CHEMBL121626	TOLFENAMIC ACID	2	20,424

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

ChEMBL bioactivities

64 potent at pChembl≥5 of 84 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	ROFECOXIB
7.68	IC50	21	nM	DUP-697
7.58	IC50	26	nM	LOXOPROFEN TRANS ALCOHOL
7.40	IC50	40	nM	CHEMBL254418
7.24	IC50	58	nM	CHEMBL5568253
7.16	IC50	70	nM	INDOMETHACIN
7.12	IC50	75	nM	CHEMBL5565096
6.87	IC50	134	nM	CHEMBL5568511
6.84	IC50	144	nM	CHEMBL5568474
6.81	Kd	153.5	nM	CHEMBL5653589
6.81	ED50	153.5	nM	CHEMBL5653589
6.72	IC50	190	nM	CHEMBL5199117
6.62	IC50	240	nM	CHEMBL5207189
6.55	IC50	280	nM	CELECOXIB
6.53	IC50	293	nM	CELECOXIB
6.52	IC50	300	nM	LOXOPROFEN TRANS ALCOHOL
6.43	IC50	367	nM	CHEMBL4448990
6.41	IC50	390	nM	LOXOPROFEN TRANS ALCOHOL
6.35	Kd	449.1	nM	CHEMBL3752910
6.35	ED50	449.1	nM	CHEMBL3752910
6.31	IC50	490	nM	CHEMBL5193981
6.29	IC50	513	nM	CHEMBL4441570
6.27	IC50	540	nM	CELECOXIB
6.26	IC50	550	nM	CHEMBL5173923
6.25	IC50	560	nM	CHEMBL5191029
6.21	IC50	610	nM	INDOMETHACIN
6.04	IC50	915	nM	CHEMBL4474644
6.03	IC50	930	nM	CHEMBL5170447
6.01	IC50	980	nM	CHEMBL4754218
5.96	IC50	1100	nM	VALDECOXIB
5.93	IC50	1170	nM	TOLFENAMIC ACID
5.85	IC50	1400	nM	CHEMBL5187847
5.85	IC50	1410	nM	TOLFENAMIC ACID
5.72	IC50	1910	nM	CHEMBL5206236
5.70	IC50	2010	nM	CHEMBL5207774
5.68	IC50	2100	nM	CHEMBL4794507
5.64	IC50	2310	nM	CHEMBL5189018
5.62	IC50	2400	nM	CHEMBL5570209
5.52	IC50	3000	nM	ROFECOXIB
5.52	IC50	3010	nM	CHEMBL5178874
5.52	IC50	3000	nM	CHEMBL5590309
5.50	IC50	3160	nM	CHEMBL5171524
5.45	IC50	3550	nM	CHEMBL5183520
5.37	IC50	4230	nM	CHEMBL4779865
5.36	IC50	4370	nM	CHEMBL5199286
5.30	IC50	4950	nM	CHEMBL5184694
5.26	IC50	5520	nM	CHEMBL5208621
5.24	IC50	5800	nM	CHEMBL5191175
5.20	IC50	6290	nM	CHEMBL4742170
5.20	IC50	6380	nM	CHEMBL5199367

PubChem BioAssay actives

61 with measured affinity, of 308 total; 50 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-methylsulfonylphenyl)-4-phenyl-2H-furan-5-one	1565363: Inhibition of COX2 (unknown origin)	ic50	0.0200	uM
5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene	2067621: Inhibition of COX-2 (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	0.0210	uM
(2S)-2-[4-[[(1R,2S)-2-hydroxycyclopentyl]methyl]phenyl]propanoic acid	1906169: Inhibition of human recombinant COX-2 using [1-14C] arachidonic acid as substrate preincubated for 15 mins followed by substrate addition	ic50	0.0260	uM
N-hydroxy-4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzenesulfonamide;hydrate	382070: Inhibition of human recombinant cyclooxygenase 2	ic50	0.0400	uM
4-[[2-(3-chlorophenyl)-5-methyl-3-oxo-1H-pyrazol-4-yl]methyl]-N-hydroxybenzamide	2067621: Inhibition of COX-2 (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	0.0580	uM
Indomethacin	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	0.0700	uM
N-hydroxy-4-[(5-methyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]benzamide	2067621: Inhibition of COX-2 (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	0.0750	uM
4-[(5-ethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]-N-hydroxybenzamide	2067621: Inhibition of COX-2 (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	0.1340	uM
4-[(5-tert-butyl-3-oxo-2-phenyl-1H-pyrazol-4-yl)methyl]-N-hydroxybenzamide	2067621: Inhibition of COX-2 (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	0.1440	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148791: Binding affinity to human MT-CO2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1535	uM
2-(3-chloro-2-methylanilino)-N-[(3,4-dihydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.1900	uM
2-(3-chloro-2-methylanilino)-N-[(3,4-dihydroxyphenyl)methyl]-5-fluorobenzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.2400	uM
Celecoxib	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	0.2800	uM
N-(4-chlorophenyl)-N-(3-oxocyclohexen-1-yl)acetamide	1565303: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha incubated for 2 mins using arachidonic acid as substrate by ELISA	ic50	0.3670	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148791: Binding affinity to human MT-CO2 incubated for 45 mins by Kinobead based pull down assay	kd	0.4491	uM
2-(3-chloro-2-methylanilino)-N-[(4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.4900	uM
3-(4-chloroanilino)cyclohex-2-en-1-one	1565303: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha incubated for 2 mins using arachidonic acid as substrate by ELISA	ic50	0.5130	uM
2-(3-chloroanilino)-N-[(4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.5500	uM
2-(3-chloro-2-methylanilino)-N-[(3-fluoro-4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.5600	uM
tert-butyl N-(4-chlorophenyl)-N-(3-oxocyclohexen-1-yl)carbamate	1565303: Inhibition of recombinant human COX2 assessed as reduction in PGF2alpha incubated for 2 mins using arachidonic acid as substrate by ELISA	ic50	0.9150	uM
2-(3-chloro-2-methylanilino)-5-fluoro-N-[(3-fluoro-4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	0.9300	uM
4-[3-[2-(4-methylphenyl)-2-oxoethyl]-2,5-dioxopyrrolidin-1-yl]benzenesulfonamide	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	0.9800	uM
4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzenesulfonamide	382070: Inhibition of human recombinant cyclooxygenase 2	ic50	1.1000	uM
2-(3-chloro-2-methylanilino)benzoic acid	1862082: Inhibition of COX-2 (unknown origin)	ic50	1.1700	uM
2-[3-(4-fluorophenyl)-6-oxo-4,5-dihydropyridazin-1-yl]-4-(4-methoxyphenyl)-1-methyl-6-oxopyrimidine-5-carbonitrile	1849642: Inhibition of COX-2 (unknown origin)	ic50	1.4000	uM
2-(3-chloro-2-methylanilino)-N-[4-(2-hydroxyethylamino)phenyl]benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	1.9100	uM
2-anilino-N-(4-hydroxyphenyl)benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	2.0100	uM
4-[3-[2-(4-methoxyphenyl)-2-oxoethyl]-2,5-dioxopyrrolidin-1-yl]benzenesulfonamide	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	2.1000	uM
2-(3-chloro-2-methylanilino)-N-(4-piperazin-1-ylphenyl)benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	2.3100	uM
5,6-difluoro-1-methyl-N-[(E)-1-pyrimidin-2-ylethylideneamino]benzimidazol-2-amine	2103481: Inhibition of COX2 (unknown origin)	ic50	2.4000	uM
5,6-difluoro-N-[(E)-1-(5-fluoro-2-pyridinyl)ethylideneamino]-1-methylbenzimidazol-2-amine	2103481: Inhibition of COX2 (unknown origin)	ic50	3.0000	uM
2-(2,6-dichloro-3-methylanilino)-N-[(4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	3.0100	uM
2-(3-chloro-2-methylanilino)-N-[4-(4-methylpiperazin-1-yl)phenyl]benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	3.1600	uM
2-(3-chloro-2-methylanilino)-N-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	3.5500	uM
4-(2,5-dioxo-3-phenacylpyrrolidin-1-yl)benzenesulfonamide	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	4.2300	uM
2-(3-chloro-2-methylanilino)-N-[4-(4-ethylpiperazin-1-yl)phenyl]benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	4.3700	uM
2-(2,3-dimethylanilino)-N-[(4-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	4.9500	uM
2-(3-chloro-2-methylanilino)-N-[(2-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	5.5200	uM
2-(3-chloro-2-methylanilino)-N-[(4-hydroxyphenyl)methyl]pyridine-3-carboxamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	5.8000	uM
4-[3-[2-(4-chlorophenyl)-2-oxoethyl]-2,5-dioxopyrrolidin-1-yl]benzenesulfonamide	1717039: Inhibition of recombinant human COX2 expressed in baculovirus infected Sf21 cells using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method	ic50	6.2900	uM
N-[4-(4-acetylpiperazin-1-yl)phenyl]-2-(3-chloro-2-methylanilino)benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	6.3800	uM
2-(3-chloro-2-methylanilino)-N-[(3-hydroxyphenyl)methyl]benzamide	1885558: Inhibition of human COX-2 assessed as by fluorescence based microplate reader assay	ic50	6.7900	uM
2-(3-chloro-2-methylanilino)-N-[4-(4-propylpiperazin-1-yl)phenyl]benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	7.3700	uM
N-[4-(4-butylpiperazin-1-yl)phenyl]-2-(3-chloro-2-methylanilino)benzamide	1862082: Inhibition of COX-2 (unknown origin)	ic50	8.3000	uM
8-(3,5-dimethoxyphenyl)-4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]furo[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-8-(4-methylphenyl)furo[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-8-phenylfuro[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM
8-(4-chlorophenyl)-4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]furo[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM
8-(3-chlorophenyl)-4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]furo[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-8-(4-fluorophenyl)furo[2,3-h]chromen-2-one	1872735: Inhibition of cox-2 (unknown origin) incubated for 5 mins by 96-well plate method	ic50	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	4
Valproic Acid	increases methylation, decreases expression, decreases methylation, increases expression	4
Zidovudine	decreases expression, increases expression	3
1-Methyl-4-phenylpyridinium	decreases expression	3
bisphenol A	decreases expression, increases expression, decreases reaction, increases abundance	2
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
Arsenic	increases expression, decreases expression, increases abundance	2
Atrazine	decreases expression	2
Cadmium	increases abundance, increases expression	2
Copper	affects metabolic processing, decreases expression	2
Doxorubicin	affects expression, decreases activity	2
Hydrogen Peroxide	affects cotreatment, affects reaction, decreases expression, decreases reaction	2
Paraquat	decreases expression, affects cotreatment, affects reaction, increases expression, decreases reaction	2
Dronabinol	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Tretinoin	increases expression, decreases expression, affects cotreatment	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
glycidyl methacrylate	decreases expression	1
di-n-octyl phthalate	affects expression	1
arsenite	affects binding, increases reaction	1
3,3’-diindolylmethane	decreases expression, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
3-methyladenine	decreases expression, decreases reaction	1
acipimox	increases expression	1
2-chloroethyl ethyl sulfide	increases expression	1
tris(chloroethyl)phosphate	increases abundance, increases expression	1
dimethoxyethyl phthalate	decreases expression	1

ChEMBL screening assays

47 unique, capped per target: 41 binding, 5 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1693371	Binding	Inhibition of human COX-2 at 10 uM by ELISA relative to licofelone	Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives. — Eur J Med Chem
CHEMBL4181304	ADMET	Inhibition of recombinant human N-terminal His-tagged COX2 expressed in baculovirus infected Sf21 cells at 10 uM using arachidonic acid as substrate pretreated for 15 mins followed by substrate addition measured after 5 mins relative to con	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
CHEMBL5546324	Toxicity	Inhibition of COX2 (unknown origin)	Lead Compound Development of SRC-3 Inhibitors with Improved Pharmacokinetic Properties and Anticancer Efficacy. — J Med Chem

Clinical trials (associated diseases)

325 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)
NCT00077805	PHASE4	COMPLETED	PREVAIL: PREvention of VTE After Acute Ischemic Stroke With LMWH Enoxaparin ( - VTE: Venous Thromboembolism - LMWH: Low Molecular Weight Heparin)
NCT00328640	PHASE4	COMPLETED	Quality Improvement in Stroke Prevention (QUISP)
NCT00697151	PHASE4	COMPLETED	Patent Foramen Ovale in Cryptogenic Stroke Study
NCT00747279	PHASE4	UNKNOWN	Comparison of Two Strategies for Glycemic Control in Acute Ischemic Stroke
NCT00754429	PHASE4	COMPLETED	The Effect of Losartan Versus Amlodipine-based Therapy in Ischemic Stroke (0954-338)(COMPLETED)
NCT00868283	PHASE4	COMPLETED	The Safety and Efficacy of Cerebrolysin in Patients With Acute Ischemic Stroke
NCT00874601	PHASE4	UNKNOWN	Valsartan Efficacy on Modest Blood Pressure Reduction in Acute Ischemic Stroke
NCT00931788	PHASE4	COMPLETED	Preventing Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack
NCT00966316	PHASE4	COMPLETED	Establishment and Evaluation to the Effects of a Clinical Pathway for Acute Ischemic Stroke
NCT01088672	PHASE4	COMPLETED	Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO)
NCT01097967	PHASE4	UNKNOWN	Sleep Disordered Breathing in Transient Ischemic Attack (TIA)/Ischemic Stroke and Continuous Positive Airway Pressure (CPAP) Treatment Efficacy
NCT01109836	PHASE4	COMPLETED	Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke
NCT01188824	PHASE4	COMPLETED	The Safety and Efficacy of Cilostazol in Ischemic Stroke Patients With Peripheral Arterial Disease (SPAD Study)
NCT01429350	PHASE4	COMPLETED	Assess the Penumbra System in the Treatment of Acute Stroke
NCT01463878	PHASE4	TERMINATED	Enteral Nutrition and Glycemic Variability Neurological Intensive Care Unit Study
NCT01758536	PHASE4	UNKNOWN	Efficacy Study of Huatuo Zaizao Pills in Improving of Neural Function in Acute Ischemic Stroke
NCT01762163	PHASE4	COMPLETED	Efficacy and Safety of Qizhitongluo Capsule in the Recovery Phase of Ischemic Stroke
NCT01862978	PHASE4	UNKNOWN	Safety and Efficacy of Heparin and Nadroparin in the Acute Phase of Ischemic Stroke
NCT01863277	PHASE4	UNKNOWN	Safety Study of Melatonin in Stroke Patients
NCT01919671	PHASE4	COMPLETED	Tongxinluo Capsule in Ischemic Stroke Patients（TISS)
NCT01958957	PHASE4	COMPLETED	A Safety Study of Ginkgolides Meglumine Injection in the Treatment of Ischemic Stroke.
NCT02046031	PHASE4	COMPLETED	Preliminary Study of Pharmacokinetics of Ginkgolides Meglumine Injection.
NCT02122718	PHASE4	COMPLETED	XILO-FIST, the Effect of Allopurinol on the Brain Heart and Blood Pressure After Stroke
NCT02225834	PHASE4	COMPLETED	Atorvastatin in Acute Stroke Treatment
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