COPS6

Summary

COPS6 (COP9 signalosome subunit 6, HGNC:21749) is a protein-coding gene on chromosome 7q22.1, encoding COP9 signalosome complex subunit 6 (Q7L5N1). Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr.

Source: NCBI Gene 10980 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 63 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈7% of expected missense variation)
• GTEx eGene: eQTL in 17 tissues, sQTL in 1 (q < 0.05)
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.37 (moderately constrained)
• MANE Select transcript: NM_006833
• Interaction hub: 2,138 STRING partners (top 6% of genes corpus-wide)
• Notable: 63 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21749
Approved symbol	COPS6
Name	COP9 signalosome subunit 6
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MOV34-34KD, CSN6
Ensembl gene	ENSG00000168090
Ensembl biotype	protein_coding
OMIM	614729
Entrez	10980

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 23 protein_coding, 9 nonsense_mediated_decay, 6 retained_intron

MANE Select: ENST00000303904

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 4, TSL 5: 1

ENST00000303904, ENST00000418625, ENST00000419210, ENST00000426712, ENST00000465027, ENST00000468499, ENST00000472107, ENST00000474823, ENST00000483891, ENST00000496358, ENST00000908037, ENST00000908038, ENST00000908039, ENST00000908040, ENST00000908041, ENST00000908042, ENST00000908043, ENST00000908044, ENST00000908045, ENST00000920061, ENST00000920062, ENST00000920063, ENST00000920064, ENST00000920065, ENST00000920066, ENST00000920067, ENST00000920068, ENST00000955918, ENST00001006836, ENST00001006837, ENST00001011473, ENST00001077118, ENST00001077119, ENST00001077120, ENST00001077122, ENST00001077124, ENST00001077125, ENST00001139345

RefSeq mRNA: 1 — MANE Select: NM_006833 NM_006833

CCDS: CCDS5682

Canonical transcript exons

ENST00000303904 — 10 exons

Exon	Start	End
ENSE00001145112	100091649	100092187
ENSE00001145117	100088969	100089066
ENSE00003505400	100090902	100090949
ENSE00003506136	100091038	100091152
ENSE00003519510	100091238	100091330
ENSE00003560042	100089290	100089415
ENSE00003597532	100090399	100090487
ENSE00003603096	100089615	100089746
ENSE00003635662	100090592	100090654
ENSE00003672033	100091420	100091520

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6313 / max 205.6533, expressed in 1812 samples.

Highest expression (Bgee): stromal cell of endometrium, apex of heart, hindlimb stylopod muscle, frontal lobe, lower esophagus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

COPS6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.7e-16	-0.29	7:100090346:T:C
Cells EBV-transformed lymphocytes	eqtl	2.2e-16	-0.78	7:100090346:T:C
Testis	eqtl	8.5e-15	-0.70	7:100086903:G:A
Artery Tibial	eqtl	5.9e-08	-0.10	7:100040221:G:T
Spleen	eqtl	3.0e-07	-0.39	7:100163962:C:A
Adipose Subcutaneous	eqtl	6.4e-07	-0.13	7:100041777:C:T
Esophagus Muscularis	eqtl	7.2e-06	-0.11	7:100018668:T:C
Nerve Tibial	eqtl	9.4e-05	-0.10	7:100053744:C:G
Skin Sun Exposed Lower leg	eqtl	1.5e-04	-0.17	7:100121789:G:A
Skin Not Sun Exposed Suprapubic	eqtl	7.3e-04	-0.23	7:99948598:T:C
Spleen	sqtl	2.5e-03	+0.76	7:100121789:G:A
Muscle Skeletal	eqtl	2.6e-03	-0.09	7:100072482:G:T
Heart Atrial Appendage	eqtl	8.0e-03	-0.09	7:100065893:A:G
Brain Spinal cord cervical c-1	eqtl	1.9e-02	-1.71	7:99471707:A:C
Brain Cerebellar Hemisphere	eqtl	2.1e-02	+0.10	7:100121877:T:C
Artery Aorta	eqtl	2.6e-02	-0.09	7:100041777:C:T
Brain Hypothalamus	eqtl	3.5e-02	+0.25	7:100008513:A:AG
Brain Nucleus accumbens basal ganglia	eqtl	4.1e-02	-0.32	7:99148607:TAA:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
79918	23.6313	1812

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.25	gold quality
apex of heart	UBERON:0002098	97.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.78	gold quality
right frontal lobe	UBERON:0002810	97.74	gold quality
lower esophagus	UBERON:0013473	97.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.73	gold quality
adenohypophysis	UBERON:0002196	97.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.68	gold quality
body of uterus	UBERON:0009853	97.67	gold quality
nucleus accumbens	UBERON:0001882	97.65	gold quality
ectocervix	UBERON:0012249	97.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.56	gold quality
cerebellar hemisphere	UBERON:0002245	97.53	gold quality
cerebellar cortex	UBERON:0002129	97.51	gold quality
smooth muscle tissue	UBERON:0001135	97.49	gold quality
prefrontal cortex	UBERON:0000451	97.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.45	gold quality
endocervix	UBERON:0000458	97.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.39	gold quality
caudate nucleus	UBERON:0001873	97.38	gold quality
popliteal artery	UBERON:0002250	97.38	gold quality
tibial artery	UBERON:0007610	97.38	gold quality
pituitary gland	UBERON:0000007	97.37	gold quality
right adrenal gland	UBERON:0001233	97.37	gold quality
left uterine tube	UBERON:0001303	97.33	gold quality
gastrocnemius	UBERON:0001388	97.32	gold quality
left coronary artery	UBERON:0001626	97.32	gold quality
putamen	UBERON:0001874	97.32	gold quality
right atrium auricular region	UBERON:0006631	97.31	gold quality
esophagus	UBERON:0001043	97.29	gold quality
ventricular zone	UBERON:0003053	97.29	gold quality
left adrenal gland	UBERON:0001234	97.26	gold quality
descending thoracic aorta	UBERON:0002345	97.26	gold quality
cingulate cortex	UBERON:0003027	97.26	gold quality
left adrenal gland cortex	UBERON:0035825	97.26	gold quality
right uterine tube	UBERON:0001302	97.25	gold quality
aorta	UBERON:0000947	97.24	gold quality
right ovary	UBERON:0002118	97.24	gold quality
muscle of leg	UBERON:0001383	97.22	gold quality
anterior cingulate cortex	UBERON:0009835	97.21	gold quality
right adrenal gland cortex	UBERON:0035827	97.21	gold quality
ganglionic eminence	UBERON:0004023	97.20	gold quality
heart left ventricle	UBERON:0002084	97.19	gold quality
coronary artery	UBERON:0001621	97.18	gold quality
amygdala	UBERON:0001876	97.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.16	gold quality
right coronary artery	UBERON:0001625	97.15	gold quality
thoracic aorta	UBERON:0001515	97.13	gold quality
left ovary	UBERON:0002119	97.12	gold quality
islet of Langerhans	UBERON:0000006	97.11	gold quality
ascending aorta	UBERON:0001496	97.11	gold quality
cardiac ventricle	UBERON:0002082	97.09	gold quality
lower esophagus mucosa	UBERON:0035834	97.07	gold quality
esophagus mucosa	UBERON:0002469	97.03	gold quality
cerebellum	UBERON:0002037	97.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.95	gold quality
cardiac atrium	UBERON:0002081	96.91	gold quality
adrenal cortex	UBERON:0001235	96.88	gold quality
tibial nerve	UBERON:0001323	96.88	gold quality
mucosa of stomach	UBERON:0001199	96.84	gold quality
metanephros cortex	UBERON:0010533	96.84	gold quality
right lobe of thyroid gland	UBERON:0001119	96.81	gold quality
heart	UBERON:0000948	96.79	gold quality
spinal cord	UBERON:0002240	96.77	gold quality
endometrium epithelium	UBERON:0004811	96.76	gold quality
body of stomach	UBERON:0001161	96.74	gold quality
cortical plate	UBERON:0005343	96.72	gold quality
muscle organ	UBERON:0001630	96.67	gold quality
skeletal muscle organ	UBERON:0014892	96.67	gold quality
neocortex	UBERON:0001950	96.61	gold quality
frontal cortex	UBERON:0001870	96.56	gold quality
hypothalamus	UBERON:0001898	96.56	gold quality
left lobe of thyroid gland	UBERON:0001120	96.54	gold quality
sigmoid colon	UBERON:0001159	96.49	gold quality
adrenal gland	UBERON:0002369	96.47	gold quality
gluteal muscle	UBERON:0002000	96.45	gold quality
mucosa of transverse colon	UBERON:0004991	96.44	gold quality
tongue squamous epithelium	UBERON:0006919	96.42	gold quality
embryo	UBERON:0000922	96.38	gold quality
peritoneum	UBERON:0002358	96.38	gold quality
omental fat pad	UBERON:0010414	96.38	gold quality
body of pancreas	UBERON:0001150	96.36	gold quality
gall bladder	UBERON:0002110	96.35	gold quality
minor salivary gland	UBERON:0001830	96.32	gold quality
forebrain	UBERON:0001890	96.32	gold quality
left testis	UBERON:0004533	96.32	gold quality
granulocyte	CL:0000094	96.31	gold quality
central nervous system	UBERON:0001017	96.28	gold quality
brain	UBERON:0000955	96.27	gold quality
telencephalon	UBERON:0001893	96.26	gold quality
prostate gland	UBERON:0002367	96.26	gold quality
ovary	UBERON:0000992	96.24	gold quality
right testis	UBERON:0004534	96.24	gold quality
thyroid gland	UBERON:0002046	96.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.21	gold quality
transverse colon	UBERON:0001157	96.14	gold quality
cerebral cortex	UBERON:0000956	96.12	gold quality
saliva-secreting gland	UBERON:0001044	96.11	gold quality
rectum	UBERON:0001052	96.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	24.08
E-MTAB-8498	no	566.72
E-GEOD-124858	no	277.26
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	186.1
Frontal cortex	tissue	168.9
Tongue	tissue	142.6
Skeletal muscle	tissue	126.9	not detected
Pons	tissue	104.4
Parathyroid gland	tissue	94.7	medium
Heart muscle	tissue	92.9	medium
Thalamus	tissue	92.6
Midbrain	tissue	88.0
Superior colliculi	tissue	87.8
Medulla oblongata	tissue	87.3
Substantia nigra	tissue	87.0
Spinal cord	tissue	85.8
Hypothalamus	tissue	80.4
Epididymis	tissue	79.3	high
Cerebral cortex	tissue	78.2	high
Motor cortex	tissue	78.2
Putamen	tissue	78.2
Hippocampal formation	tissue	77.9
Periaqueductal gray	tissue	77.5
Somatosensory cortex	tissue	77.2
Prefrontal cortex	tissue	75.7
Pituitary gland	tissue	75.0
Septum	tissue	74.8
Smooth muscle	tissue	73.3	medium
Ovary	tissue	72.6	medium
Nucleus accumbens	tissue	72.2
Vagina	tissue	71.2	high
Occipital cortex	tissue	70.3
Ventral forebrain	tissue	70.1
Seminal vesicle	tissue	69.8	medium
Esophagus	tissue	69.5	medium
Entorhinal cortex	tissue	69.4
Temporal cortex	tissue	69.3
Basal ganglia	tissue	69.0	medium
Fallopian tube	tissue	68.5	high
Retrosplenial and cingulate cortex	tissue	68.1
Liver	tissue	66.6	not detected
Choroid plexus	tissue	66.4
Kidney	tissue	66.1	high
Corpus callosum	tissue	66.1
Locus coeruleus	tissue	66.0
Urinary bladder	tissue	65.2	high
Retrosplenial cortex	tissue	64.8
Cervix	tissue	63.9	high
Cerebellum	tissue	62.2	medium
Postcentral gyrus	tissue	62.0
Salivary gland	tissue	61.2	high
Adrenal gland	tissue	61.0	low
Amygdala	tissue	60.3
Placenta	tissue	60.1	low
Insular cortex	tissue	60.1
Thymus	tissue	58.8
Hippocampus	tissue	57.0	medium
Retina	tissue	56.9
Thyroid gland	tissue	56.8	medium
Tonsil	tissue	56.8	medium
Endometrium 1	tissue	56.3	low
Adipose tissue	tissue	55.5	low
Pancreas	tissue	55.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (96.2), Ventral spinal cord (85.8), Dorsal hippocampus (77.9), Lateral funiculus (white matter) (76.9), Dorsal spinal cord (76.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting COPS6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-3085-5P	97.72	65.43	544
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-4280	96.44	67.69	473
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725
HSA-MIR-6802-5P	94.94	65.95	366

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.373, missense Z 2.49 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000303904 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈7% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:100,088,991–100,089,413	76 / 97.9	0.78	no
7:100,089,414–100,089,688	4 / 29.8	0.13	yes (p 2.3e-06)
7:100,089,689–100,091,786	222 / 309.0	0.72	no
DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H522 (-3.268), GCIY (-2.807), EFO-21 (-2.622), SNU-5 (-2.599), NCI-H647 (-2.569), TF-1 (-2.554), NCI-H1693 (-2.499), RERF-GC-1B (-2.479), NCI-H1581 (-2.473), HD-MY-Z (-2.467), Caov-4 (-2.456), IST-MES2 (-2.455), SLR 23 (-2.452), COR-L311 (-2.433), NCI-H82 (-2.402).

Literature-anchored findings (GeneRIF, showing 23)

• critical role of caspase 8 in the processing of CSN6. (PMID:17337451)
• For the first time our data demonstrate that CSN-mediated deneddylation can be regulated by active Casp3 and that the CSN executes a specific function during the apoptotic process. (PMID:18060501)
• loss of CSN6 enhances p53-mediated tumor suppression in vivo and CSN6 plays an important role in regulating DNA damage-associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway (PMID:21317535)
• COPS6 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Data suggest that CSN6 is an important negative regulator of p57 (Kip2) , and that overexpression of CSN6 in many types of cancer could lead to decreased expression of p57 (Kip2) and result in promoted cancer cell growth. (PMID:23187808)
• Analyses of the pseudo metal-binding motif in CSN6 suggest that the loss of two key histidine residues may contribute to the lack of catalytic activity in CSN6. (PMID:25242525)
• CSN6 interacts with p27(Kip1) and facilitates ubiquitin-mediated degradation of p27(Kip1). (PMID:25945542)
• CSN6 positively regulates c-Jun in a MEKK1-dependent manner (PMID:26237449)
• Findings indicate that the deregulation of beta-catenin by extracellular signal-regulated kinase 2 (ERK2)-activated CSN6 protein is important for colorectal cancer (CRC) development. (PMID:26267535)
• our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development. (PMID:26318036)
• High CSN6 expression is associated with metastasis of glioblastoma. (PMID:27546621)
• The overexpression of CSN6 reduced the effect of quercetin treatment on HT29 cells, suggesting that quercetininduced apoptosis may involve the AktCSN6Myc signaling axis in HT29 cells. (PMID:27748879)
• CSN6 expression is a potential biomarker for predicting cancer recurrence and clinical survival in upper tract urothelial carcinoma. (PMID:31339657)
• Overexpression of CSN6 promotes the epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma. (PMID:31422034)
• Study shows that Cullin-RING Ligase-2 (CRL2) activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Synergising cryo-electron microscopy with mass spectrometry, study identified sensory regions of the COP9 signalosome that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. (PMID:31444342)
• High CSN6 expression is associated with glioblastoma. (PMID:32134157)
• CSN6-TRIM21 axis instigates cancer stemness during tumorigenesis. (PMID:32225170)
• CSN6 inhibition suppresses pancreatic adenocarcinoma metastasis via destabilizing the c-Fos protein. (PMID:32289284)
• CSN6 promotes malignant progression of oral squamous cell carcinoma by down-regulating TIMP-2. (PMID:32495877)
• CSN6 promotes the cell migration of breast cancer cells by positively regulating Snail1 stability. (PMID:33162808)
• CUL4A regulates endometrial cancer cell proliferation, invasion and migration by interacting with CSN6. (PMID:33179082)
• CSN6 Mediates Nucleotide Metabolism to Promote Tumor Development and Chemoresistance in Colorectal Cancer. (PMID:36512632)
• CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation. (PMID:38308184)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cops6	ENSMUSG00000019494
rattus_norvegicus	Cops6	ENSRNOG00000001346
drosophila_melanogaster	CSN6	FBGN0028837
caenorhabditis_elegans		WBGENE00000818

Paralogs (2): PSMD7 (ENSG00000103035), EIF3F (ENSG00000175390)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1349439) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased mortality induced by gamma-irradiation	1
increased cellular sensitivity to gamma-irradiation induced cell death	1
decreased incidence of tumors by ionizing radiation induction	1
increased sensitivity to induced cell death	1
increased thymocyte apoptosis	1
embryonic lethality between implantation and somite formation, complete penetrance	1
embryonic lethality during organogenesis, complete penetrance	1
embryonic lethality between somite formation and embryo turning, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	A7TX81	99.7%	Diamond
Pongo abelii	Q5REY0	99.7%	Diamond
Bos taurus	A6QQ21	99.4%	Diamond
Xenopus tropicalis	Q07G98	97.8%	Diamond
Xenopus laevis	Q6NUC2	97.8%	Diamond
Arabidopsis thaliana	Q8W206	89.2%	Diamond
Oryza sativa Japonica Group	Q6ZKM2	81.1%	Diamond
Pyricularia oryzae 70-15	A4R0E5	73.3%	Diamond
Dictyostelium discoideum	Q54C92	43.8%	Diamond
Aspergillus nidulans FGSC A4	Q5BB47	34.7%	Diamond
Neurospora crassa OR74A	Q7S8C8	34.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR25	ncRNA	407014
MIR93	ncRNA	407050
MCM7	protein-coding	4176
ZNF3	protein-coding	7551
ZKSCAN1	protein-coding	7586
ZSCAN21	protein-coding	7589
MIR106B	ncRNA	406900
TAF6	protein-coding	6878
AP4M1	protein-coding	9179
CNPY4	protein-coding	245812
MBLAC1	protein-coding	255374

Protein

Protein identifiers

COP9 signalosome complex subunit 6 — Q7L5N1 (reviewed: Q7L5N1)

Alternative names: JAB1-containing signalosome subunit 6, MOV34 homolog, Vpr-interacting protein

All UniProt accessions (4): Q7L5N1, C9JQK5, E7EM64, H7C3T0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes COP1 through reducing COP1 auto-ubiquitination and decelerating COP1 turnover rate, hence regulates the ubiquitination of COP1 targets.

Subunit / interactions. Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1. In the complex, it probably interacts directly with COPS2, COPS4, COPS5, COPS7 (COPS7A or COPS7B) and COPS9 isoform 1. Interacts with the translation initiation factor EIF3S6. Interacts weakly with RBX1. Directly interacts with COP1 and 14-3-3 protein sigma/SFN. Interacts with ERCC6. (Microbial infection) Interacts with the HIV-1 protein Vpr.

Subcellular location. Nucleus. Cytoplasm Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed.

Similarity. Belongs to the peptidase M67A family. CSN6 subfamily.

RefSeq proteins (1): NP_006824* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR024969	EIF3F/CSN6-like_C	Domain
IPR033859	MPN_CSN6	Family
IPR037518	MPN	Domain

Pfam: PF01398, PF13012

UniProt features (18 total): strand 9, helix 5, chain 1, domain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

29 structures by resolution:

PDB	Title	Method	Resolution (Å)
4QFT	Structure of COP9 signalosome complex subunit 6	X-RAY DIFFRACTION	1.76
4R14	Crystal structure of human CSN6 MPN domain	X-RAY DIFFRACTION	2.6
9QO4	Dissociation-state-3 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex	ELECTRON MICROSCOPY	2.95
9EFQ	Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-2	ELECTRON MICROSCOPY	2.96
9PH4	Cryo-EM structure of COP9 signalosome in complex with CSN5i-1a	ELECTRON MICROSCOPY	3
9QO6	9-subunit COP9 signalosome complex	ELECTRON MICROSCOPY	3
9EFV	Cryo-EM structure of CSN-N8CUL1 in complex with CSN5i-3	ELECTRON MICROSCOPY	3.03
9EFM	Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-1	ELECTRON MICROSCOPY	3.16
9QO1	Activated 9-subunit COP9 signalosome and neddylated SCF (SKP1-SKP2-CKS1) complex structure	ELECTRON MICROSCOPY	3.23
9QO0	Pre-activated 9-subunit COP9 signalosome and neddylated SCF (Skp1-Skp2-Cks1) complex …	ELECTRON MICROSCOPY	3.26
9E77	Cryo-EM structure of CSN-N8 in complex with CSN5i-3	ELECTRON MICROSCOPY	3.3
9E81	Cryo-EM structure of COP9 signalosome in complex with CSN5i-3	ELECTRON MICROSCOPY	3.3
9EG8	Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-4A	ELECTRON MICROSCOPY	3.39
9E5Z	Cryo-EM structure of COP9 signalosome	ELECTRON MICROSCOPY	3.4
9EG1	COP9 signalosome deneddylation complex with cullin-5	ELECTRON MICROSCOPY	3.52
4D10	Crystal structure of the COP9 signalosome	X-RAY DIFFRACTION	3.8
9QO2	Dissociation-state-1 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex	ELECTRON MICROSCOPY	3.8
9EGL	Cryo-EM structure of COP9 signalosome precatalytic state with neddylated cullin-3	ELECTRON MICROSCOPY	3.93
9QO5	Dissociation-state-4 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex	ELECTRON MICROSCOPY	4
4D18	Crystal structure of the COP9 signalosome	X-RAY DIFFRACTION	4.08
8H38	Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN(mutate) complex	ELECTRON MICROSCOPY	4.25
9QO3	Dissociation-state-2 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex	ELECTRON MICROSCOPY	4.6
4WSN	Crystal structure of the COP9 signalosome, a P1 crystal form	X-RAY DIFFRACTION	5.5
6R7I	Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome	ELECTRON MICROSCOPY	5.9
8H3F	Cryo-EM Structure of the KBTBD2-CRL3-CSN complex	ELECTRON MICROSCOPY	6.73
8H3A	Cryo-EM Structure of the KBTBD2-CRL3~N8(removed)-CSN complex	ELECTRON MICROSCOPY	7.51
6R7F	Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome	ELECTRON MICROSCOPY	8.2
6R6H	Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome	ELECTRON MICROSCOPY	8.4
6R7H	Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome	ELECTRON MICROSCOPY	8.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L5N1-F1	86.28	0.65

Human Protein Atlas

Protein class: Enzymes, Peptidases, Metallopeptidases, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-5696394	DNA Damage Recognition in GG-NER	curated
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex	curated
R-HSA-8951664	Neddylation	curated
R-HSA-8856828	Clathrin-mediated endocytosis	—
R-HSA-73894	DNA Repair	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 168 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, MORF_HDAC1, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, GOBP_PROTEIN_NEDDYLATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, MUELLER_PLURINET, MORF_CTBP1, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GCM_NF2, MORF_IKBKG, MORF_AATF

GO Biological Process (3): protein deneddylation (GO:0000338), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434)

GO Molecular Function (3): protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), COP9 signalosome (GO:0008180), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Nucleotide Excision Repair	2
Global Genome Nucleotide Excision Repair (GG-NER)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1
Clathrin-mediated endocytosis	1
Post-translational protein modification	1
Vesicle-mediated transport	1
DNA Repair	1
Metabolism of proteins	1
Membrane Trafficking	1

GO top-level categories

14 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
protein modification by small protein removal	1
protein modification by small protein conjugation	1
protein neddylation	1
regulation of protein modification by small protein conjugation or removal	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
protein deneddylation	BP	direct assay
COP9 signalosome	CC	direct assay
cytoplasm	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,138 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS6	COPS8	Q99627	845
COPS6	COPS4	Q9BT78	843
COPS6	COPS5	Q92905	835
COPS6	COPS7A	Q9UBW8	815
COPS6	COPS7B	Q9H9Q2	729
COPS6	NEDD8	Q15843	700
COPS6	COPS2	P61201	678
COPS6	GPS1	Q13098	638
COPS6	PSMD14	O00487	604
COPS6	COPS3	Q9UNS2	600
COPS6	CUL1	Q13616	593
COPS6	MPND	Q8N594	538
COPS6	CUL3	Q13618	514
COPS6	STAMBPL1	Q96FJ0	506
COPS6	COPS9	Q8WXC6	497

IntAct

Human interaction partners of COPS6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 92 partners by confidence:

Partner	Interaction type	MIscore	Records
COPS5	physical association	0.930	2
COPS4	physical association	0.920	4
COPS3	physical association	0.920	1
COPS2	association	0.880	10
RHOBTB1	association	0.730	6
SFN	association	0.650	6
BFSP2	physical association	0.560	3
CCBE1	physical association	0.560	3
SHC3	physical association	0.560	3
USHBP1	physical association	0.560	3
ZFHX3	physical association	0.560	3
BTRC	physical association	0.560	1
SMN1	physical association	0.550	2
TK1	physical association	0.550	2
MAPK1	physical association	0.540	2
KLHL18	association	0.530	1
COP1	association	0.520	2
MIF	physical association	0.400	1
ANXA1	physical association	0.370	1
ANXA7	physical association	0.370	1
CDKN1A	physical association	0.370	1
MAPK6	physical association	0.370	1
MAPKAPK3	physical association	0.370	1
SHANK3	physical association	0.370	1
TP63	physical association	0.370	1
TSG101	physical association	0.370	1
VIM	physical association	0.370	1
DDX3X	association	0.350	1
GPS1	association	0.350	1
ASH2L	physical association	0.000	1

BioGRID (765 interactions; top human partners by supporting records in a sample of 600 records): COPS5 (Reconstituted Complex; 17 records), COPS4 (Affinity Capture-MS; 15 records), CUL4A (Affinity Capture-MS; 14 records), COPS2 (Affinity Capture-MS; 12 records), COPS3 (Affinity Capture-MS; 12 records), COPS7B (Affinity Capture-MS; 11 records), COPS8 (Affinity Capture-MS; 11 records), GPS1 (Affinity Capture-MS; 11 records), COPS7A (Affinity Capture-MS; 10 records), CUL3 (Affinity Capture-MS; 9 records), DDB2 (Affinity Capture-MS; 9 records), CUL4B (Affinity Capture-MS; 8 records), DCAF11 (Affinity Capture-MS; 8 records), CUL2 (Affinity Capture-MS; 7 records), BTBD1 (Affinity Capture-MS; 6 records)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
AKT	up-regulates	COPS6	phosphorylation
AKT1	up-regulates	COPS6	phosphorylation
COPS6	“form complex”	“COP9 signalosome variant 2”	binding
COPS6	“form complex”	“COP9 signalosome variant 1”	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
CSA-POLIIa complex	13	COPS3, COPS4, COPS5, COPS7A, CUL4A, ERCC8, RBX1, COPS2, COPS6, COPS8, DDB1, GPS1, POLR2A
DDB2 complex	12	COPS7A, CUL4A, DDB1, DDB2, COPS4, COPS6, COPS8, GPS1, RBX1, COPS2, COPS3, COPS5
CSA complex	12	COPS5, COPS7A, CUL4A, DDB1, GPS1, RBX1, COPS2, COPS6, COPS8, ERCC8, COPS3, COPS4
CNS-P53 complex	9	COPS3, COPS6, COPS2, COPS4, COPS5, COPS7A, COPS8, GPS1, TP53
COP9 signalosome complex	8	COPS7A, COPS8, GPS1, COPS2, COPS3, COPS4, COPS5, COPS6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
RHOBTB1 GTPase cycle	5	36.0×	4e-05
DNA Damage Recognition in GG-NER	7	30.3×	9e-07
Formation of TC-NER Pre-Incision Complex	8	25.6×	5e-07
Cargo recognition for clathrin-mediated endocytosis	7	11.1×	4e-04
Neddylation	11	7.9×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	7	76.2×	1e-09
protein neddylation	6	49.0×	6e-07

Disease & clinical

Genetic variants

Variant evidence for COPS6: 63 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 636):

Position(s)	Effect	Δscore	Sites
7:100089067–100089068	donor_loss	1.0000	4
7:100089720	donor_gain	1.0000
7:100089750	donor_gain	1.0000
7:100089769	donor_gain	1.0000
7:100090488–100090489	donor_loss	1.0000	4
7:100090591	acceptor_gain	1.0000
7:100091139	donor_gain	1.0000
7:100091153–100091154	donor_loss	1.0000	5
7:100091227	acceptor_gain	1.0000
7:100091233	acceptor_gain	1.0000

AlphaMissense

1,189 missense substitutions predicted likely pathogenic (of 2,167 scored), across 264 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M230	9	0.967	0.998
H44	8	0.995	1.000
H54	8	0.987	0.999
D285	8	0.984	0.995
D201	8	0.983	0.997
F116	8	0.974	0.999
D135	8	0.973	0.991
F87	8	0.972	0.999
D53	8	0.965	0.999
H202	8	0.959	0.994
D173	8	0.954	0.990
F183	8	0.946	0.999
N85	8	0.933	0.998
F275	8	0.931	0.992
H139	8	0.907	0.997
F121	8	0.905	0.996
D314	8	0.828	0.969
F151	8	0.826	0.993
W124	7	0.997	1.000
E196	7	0.997	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.05e-07
Kidney Chromophobe (TCGA)	unfavorable	8.21e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.7e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00036
Lung Adenocarcinoma (TCGA)	unfavorable	0.00054

Disease associations

OMIM: gene MIM:614729 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST010703_241	Brain morphology (MOSTest)	6e-15
GCST010702_30	Subcortical volume (MOSTest)	6e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067091 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants, Occupational	affects expression	1
Cadmium	increases abundance, increases expression	1
Ivermectin	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	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
CHEMBL5651165	Binding	Binding affinity to human COPS6 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*

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F6IW	EDITGENE COPS6 Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_SJ52	HAP1 COPS6 (-) 1	Cancer cell line	Male
CVCL_SJ53	HAP1 COPS6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	Phase 4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02441894	Phase 4	COMPLETED	Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
NCT02475057	Phase 4	COMPLETED	Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists
NCT02511665	Phase 4	UNKNOWN	Metformin And Longevity
NCT02651948	Phase 4	COMPLETED	Transperineal, MRI-guided, Prostate Biopsy
NCT02721433	Phase 4	COMPLETED	4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
NCT02726009	Phase 4	COMPLETED	A Trial to Evaluate Safety of Firmagon® (Degarelix) in Indian Patients Diagnosed With Advanced Hormone-dependent Prostate Cancer
NCT02749825	Phase 4	TERMINATED	Comparison of Trelstar Versus Lupron or Zoladex in Advanced Prostate Cancer
NCT02757365	Phase 4	UNKNOWN	Efficiency Study of Aspirin to Prevent the Occurrence of Prostate Cancer
NCT02773251	Phase 4	COMPLETED	The Effect of Guardix-solution for the Prevention of Postoperative Intestinal Adhesion and Intestinal Obstruction After Laparoscopic Pelvic Cavity Surgery
NCT02812186	Phase 4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for COPS6 across ~30M SureChEMBL compounds — explore on Sugi Predict.