COX6C

Summary

COX6C (cytochrome c oxidase subunit 6C, HGNC:2285) is a protein-coding gene on chromosome 8q22.2, encoding Cytochrome c oxidase subunit 6C (P09669). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. It is a selective cancer dependency (DepMap: 46.9% of cell lines).

Cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIc, which has 77% amino acid sequence identity with mouse subunit VIc. This gene is up-regulated in prostate cancer cells. A pseudogene has been found on chromosomes 16p12.

Source: NCBI Gene 1345 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 29 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 46.9% of screened cell lines
• MANE Select transcript: NM_004374

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2285
Approved symbol	COX6C
Name	cytochrome c oxidase subunit 6C
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164919
Ensembl biotype	protein_coding
OMIM	124090
Entrez	1345

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 27 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000297564, ENST00000517682, ENST00000518171, ENST00000520271, ENST00000520468, ENST00000520517, ENST00000522934, ENST00000522940, ENST00000523016, ENST00000524245, ENST00000606245, ENST00000897774, ENST00000897775, ENST00000897776, ENST00000897777, ENST00000928967, ENST00000928968, ENST00000928969, ENST00000928970, ENST00000928971, ENST00000928972, ENST00000928973, ENST00000928974, ENST00000928975, ENST00000928976, ENST00000928977, ENST00000928978, ENST00000966738, ENST00000966739, ENST00000966740

RefSeq mRNA: 1 — MANE Select: NM_004374 NM_004374

CCDS: CCDS6284

Canonical transcript exons

ENST00000520468 — 4 exons

Exon	Start	End
ENSE00001088650	99887490	99887618
ENSE00001273958	99891908	99892052
ENSE00002091100	99877865	99878265
ENSE00002121979	99893639	99893707

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 254.6337 / max 4002.5382, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94114	178.7718	1825
94115	75.2893	1822
94112	0.4849	106
94113	0.0877	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.85	gold quality
cardiac ventricle	UBERON:0002082	99.77	gold quality
heart left ventricle	UBERON:0002084	99.77	gold quality
body of tongue	UBERON:0011876	99.77	gold quality
heart right ventricle	UBERON:0002080	99.76	gold quality
superior vestibular nucleus	UBERON:0007227	99.75	gold quality
apex of heart	UBERON:0002098	99.73	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.73	gold quality
biceps brachii	UBERON:0001507	99.72	gold quality
cardiac atrium	UBERON:0002081	99.70	gold quality
right atrium auricular region	UBERON:0006631	99.70	gold quality
diaphragm	UBERON:0001103	99.69	gold quality
nucleus accumbens	UBERON:0001882	99.69	gold quality
myocardium	UBERON:0002349	99.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.69	gold quality
superior surface of tongue	UBERON:0007371	99.68	gold quality
colonic mucosa	UBERON:0000317	99.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.67	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.67	gold quality
amygdala	UBERON:0001876	99.66	gold quality
substantia nigra pars compacta	UBERON:0001965	99.66	gold quality
ventral tegmental area	UBERON:0002691	99.66	gold quality
vena cava	UBERON:0004087	99.66	gold quality
heart	UBERON:0000948	99.65	gold quality
right frontal lobe	UBERON:0002810	99.65	gold quality
renal medulla	UBERON:0000362	99.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.64	gold quality
left ventricle myocardium	UBERON:0006566	99.64	gold quality
pharyngeal mucosa	UBERON:0000355	99.63	gold quality
prefrontal cortex	UBERON:0000451	99.63	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	3410.84
E-GEOD-89232	yes	3255.69
E-MTAB-10885	yes	2303.67
E-MTAB-8410	yes	51.23
E-MTAB-10042	yes	15.41
E-HCAD-10	yes	12.31
E-MTAB-7316	yes	11.29
E-MTAB-10596	no	1411.98
E-ENAD-17	no	1137.12
E-MTAB-7606	no	166.45
E-MTAB-10287	no	46.88
E-HCAD-5	no	2.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting COX6C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-592	96.59	67.59	817
HSA-MIR-576-3P	96.14	65.63	773

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 46.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Data found that subunits Cox6a, Cox6b and Cox7a assembled into pre-existing complex IV, while Cox4-1 and Cox6c subunits assembled into subcomplexes that may represent rate-limiting intermediates. (PMID:19843159)
• Data indicate that recombinant (r)IL-24 stimulated the mitochondrial apoptotic pathway genes Bax, Bid, Casp8, COX6C, COX7B after 36 h. (PMID:22860893)
• Within the first 3h of infection with influenza virus, significant down-regulation of hsa-miRNA-4276 is followed by a 2-fold increase in cytochrome c oxidase VIc mRNA was found to occur in human alveolar and bronchial epithelial cells. (PMID:25203353)
• Results report that a DAZAP1-targeted transcript, the cox6c mRNA, carries the E1 and E2 elements. Cox6c is a nuclear gene that encodes a subunit of complex IV in the mitochondrial respiratory chain. (PMID:29505834)
• COX6C expression driven by copy amplification of 8q22.2 regulates cell proliferation via mediation of mitosis by ROS-AMPK signaling in lung adenocarcinoma. (PMID:38242874)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cox6c	ENSMUSG00000014313

Protein

Protein identifiers

Cytochrome c oxidase subunit 6C — P09669 (reviewed: P09669)

Alternative names: Cytochrome c oxidase polypeptide VIc

All UniProt accessions (2): A0A024R9B7, P09669

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)).

Subcellular location. Mitochondrion inner membrane.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the cytochrome c oxidase subunit 6c family.

RefSeq proteins (1): NP_004365* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR034884	Cytochrome_c_oxidase_VIc/VIIs	Family
IPR037169	Cytochrome_c_oxidase_VIc_sf	Homologous_superfamily
IPR051389	Cytochrome_c_oxidase_VIc	Family

Pfam: PF02937

UniProt features (4 total): topological domain 2, chain 1, transmembrane region 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-P09669-F1	94.94	0.90

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-611105	Respiratory electron transport
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 187 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MODULE_93, MODULE_151, YANG_BREAST_CANCER_ESR1_BULK_UP, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, PUJANA_CHEK2_PCC_NETWORK, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MORF_SKP1A, ONKEN_UVEAL_MELANOMA_UP, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_ELECTRON_TRANSPORT_CHAIN, KEGG_HUNTINGTONS_DISEASE, MODULE_307

GO Biological Process (4): generation of precursor metabolites and energy (GO:0006091), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), cellular respiration (GO:0045333), oxidative phosphorylation (GO:0006119)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial membrane (GO:0031966), respiratory chain complex IV (GO:0045277), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Cellular response to chemical stress	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrial envelope	2
metabolic process	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
energy derivation by oxidation of organic compounds	1
aerobic respiration	1
proton motive force-driven ATP synthesis	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
organelle envelope lumen	1
mitochondrion	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

1446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX6C	COX5B	P10606	991
COX6C	COX7C	P15954	987
COX6C	COX7B	P24311	961
COX6C	COX5A	P20674	955
COX6C	COX8A	P10176	954
COX6C	COX6B1	P14854	913
COX6C	COX6A1	P12074	904
COX6C	COX6A2	Q02221	884
COX6C	F5H6H0	F5H6H0	858
COX6C	CCNB1IP1	Q9NPC3	800
COX6C	COXFA4	O00483	775
COX6C	COX4I1	P13073	737
COX6C	CYCS	P00001	735
COX6C	COX7A2	P14406	735
COX6C	DPT	Q07507	718

IntAct

103 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
COX6C	HTT	psi-mi:“MI:0915”(physical association)	0.670
RAC1	COX6C	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
UQCRH	COX7A2L	psi-mi:“MI:0914”(association)	0.640
SAT1	COX6C	psi-mi:“MI:0915”(physical association)	0.560
COX6C	SAT1	psi-mi:“MI:0915”(physical association)	0.560
MT-CO2	COX6C	psi-mi:“MI:0915”(physical association)	0.560
COQ2	SLC25A5	psi-mi:“MI:0914”(association)	0.530
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
COX6C	RCHY1	psi-mi:“MI:0915”(physical association)	0.370
NDUFA12	NDUFS8	psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CAPZA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CRK	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
RAB2A		psi-mi:“MI:0914”(association)	0.350
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
CHCHD10	TIMM44	psi-mi:“MI:0914”(association)	0.350

BioGRID (171): COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX6C (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J2F0, A0A1D8PLP3, A1XQT2, A5E7J0, A7TQM5, A8E7D3, A8KB87, B7Z0X7, C4YBX9, G2TRJ9, G2TRT6, O13931, O14949, O17287, O74433, O94705, P07255, P09669, P11950, P19173, P22289, P47081, P48505, P81450, Q02820, Q2L897, Q54QR8, Q5R597, Q5RK28, Q6BL60, Q6CCF6, Q6CJX2, Q6CK73, Q6CS34, Q6CWK9, Q6FW43, Q6FWE8, Q757F0, Q75FA7, Q7SGT7

Diamond homologs: A1XQT2, P04038, P09669, P11950, P11951, P80977, Q0Q4Z0, Q7YRJ8, Q7YRJ9, Q7YRK0, Q7YRK1, Q7YRK2, Q7YRK3, Q7YRK7, Q9CPQ1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COX6C	“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 105 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	11	32.6×	5e-12
Respiratory electron transport	18	22.2×	3e-17
Cytoprotection by HMOX1	9	21.5×	4e-08
TP53 Regulates Metabolic Genes	10	16.9×	4e-08
Complex I biogenesis	7	15.1×	4e-05
Mitochondrial protein degradation	7	10.4×	4e-04
Aerobic respiration and respiratory electron transport	7	8.1×	2e-03
SLC-mediated transmembrane transport	8	6.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, cytochrome c to oxygen	10	84.2×	7e-15
cellular respiration	9	42.7×	2e-10
mitochondrial electron transport, NADH to ubiquinone	6	23.6×	4e-05
aerobic respiration	8	21.8×	9e-07
generation of precursor metabolites and energy	5	18.9×	9e-04
proton motive force-driven mitochondrial ATP synthesis	6	17.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

671 predictions. Top by Δscore:

Variant	Effect	Δscore
8:99887510:TTAC:T	donor_gain	1.0000
8:99887513:CACT:C	donor_gain	1.0000
8:99887534:T:TA	donor_gain	1.0000
8:99887614:CGAAA:C	acceptor_gain	1.0000
8:99887619:C:CC	acceptor_gain	1.0000
8:99891904:ATAC:A	donor_loss	1.0000
8:99891905:TA:T	donor_loss	1.0000
8:99891907:C:CA	donor_loss	1.0000
8:99892048:CTAAC:C	acceptor_gain	1.0000
8:99887484:TATTA:T	donor_loss	0.9900
8:99887485:ATTAC:A	donor_loss	0.9900
8:99887486:TTA:T	donor_loss	0.9900
8:99887487:TA:T	donor_loss	0.9900
8:99887488:ACC:A	donor_loss	0.9900
8:99887489:CCTTT:C	donor_loss	0.9900
8:99887504:A:AC	donor_gain	0.9900
8:99887508:CT:C	donor_gain	0.9900
8:99887509:TT:T	donor_gain	0.9900
8:99887510:TT:T	donor_gain	0.9900
8:99887513:CA:C	donor_gain	0.9900
8:99887530:G:A	donor_gain	0.9900
8:99891906:A:AC	donor_gain	0.9900
8:99891907:C:CC	donor_gain	0.9900
8:99892052:CCT:C	acceptor_gain	0.9900
8:99892053:C:G	acceptor_loss	0.9900
8:99892054:T:C	acceptor_gain	0.9900
8:99892054:T:TC	acceptor_gain	0.9900
8:99887490:C:G	donor_loss	0.9800
8:99887507:A:AC	donor_gain	0.9800
8:99887508:C:CC	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022837 (8:99893236 G>A), RS1000201937 (8:99889270 C>T), RS1000228261 (8:99883478 T>C), RS1000883175 (8:99892542 A>G), RS1001154962 (8:99883772 C>T), RS1001410205 (8:99893674 C>A,G,T), RS1001445041 (8:99882533 G>C), RS1001583222 (8:99888613 G>C), RS1001667155 (8:99893395 C>T), RS1001930892 (8:99888493 C>T), RS1002067141 (8:99883168 G>A), RS1002885736 (8:99885510 C>T), RS1002918897 (8:99891411 A>G), RS1003012751 (8:99879911 C>A,T), RS1003063948 (8:99881397 T>G)

Disease associations

OMIM: gene MIM:124090 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002726_66	Glucose homeostasis traits	6.000000e-06
GCST009856_49	Leukocyte telomere length	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006830	insulin metabolic clearance rate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066369 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.92	Kd	11.97	nM	CHEMBL5653589
7.92	ED50	11.97	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148133: Binding affinity to human COX6C incubated for 45 mins by Kinobead based pull down assay	kd	0.0120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Acetaminophen	increases expression, affects cotreatment, decreases expression	2
Hydrogen Peroxide	affects cotreatment, affects reaction, decreases expression, decreases reaction	2
Lipopolysaccharides	affects cotreatment, decreases expression, affects expression, affects response to substance	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects response to substance, affects expression	1
tetrahydropalmatine	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
epigallocatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
gallocatechol	decreases expression, decreases reaction, affects cotreatment, affects reaction	1
epicatechin gallate	affects cotreatment, affects reaction, decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	affects expression	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651175	Binding	Binding affinity to human COX6C incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery