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): 62 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_006833

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: 28 — 21 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

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

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79918	23.6313	1812

Top tissues by expression

300 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting COPS6, 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-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

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

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)

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): C9JQK5, E7EM64, Q7L5N1, 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.

PDB	Method	Resolution (Å)
4QFT	X-RAY DIFFRACTION	1.76
4R14	X-RAY DIFFRACTION	2.6
9QO4	ELECTRON MICROSCOPY	2.95
9EFQ	ELECTRON MICROSCOPY	2.96
9PH4	ELECTRON MICROSCOPY	3
9QO6	ELECTRON MICROSCOPY	3
9EFV	ELECTRON MICROSCOPY	3.03
9EFM	ELECTRON MICROSCOPY	3.16
9QO1	ELECTRON MICROSCOPY	3.23
9QO0	ELECTRON MICROSCOPY	3.26
9E77	ELECTRON MICROSCOPY	3.3
9E81	ELECTRON MICROSCOPY	3.3
9EG8	ELECTRON MICROSCOPY	3.39
9E5Z	ELECTRON MICROSCOPY	3.4
9EG1	ELECTRON MICROSCOPY	3.52
4D10	X-RAY DIFFRACTION	3.8
9QO2	ELECTRON MICROSCOPY	3.8
9EGL	ELECTRON MICROSCOPY	3.93
9QO5	ELECTRON MICROSCOPY	4
4D18	X-RAY DIFFRACTION	4.08
8H38	ELECTRON MICROSCOPY	4.25
9QO3	ELECTRON MICROSCOPY	4.6
4WSN	X-RAY DIFFRACTION	5.5
6R7I	ELECTRON MICROSCOPY	5.9
8H3F	ELECTRON MICROSCOPY	6.73
8H3A	ELECTRON MICROSCOPY	7.51
6R7F	ELECTRON MICROSCOPY	8.2
6R6H	ELECTRON MICROSCOPY	8.4
6R7H	ELECTRON MICROSCOPY	8.8

Predicted structure (AlphaFold)

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

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8951664	Neddylation

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

Rollup of top-4 pathways:

Category	Pathways
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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

3042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS6	COPS5	Q92905	986
COPS6	COPS4	Q9BT78	968
COPS6	COPS8	Q99627	950
COPS6	COPS7A	Q9UBW8	946
COPS6	COPS3	Q9UNS2	874
COPS6	COPS2	P61201	829
COPS6	COPS7B	Q9H9Q2	822
COPS6	GPS1	Q13098	804
COPS6	NEDD8	Q15843	718
COPS6	EIF3H	O15372	694
COPS6	MPND	Q8N594	680
COPS6	IGF2R	P11717	665
COPS6	PSMD14	O00487	636
COPS6	CUL1	Q13616	635
COPS6	RBX1	P62877	610

IntAct

294 interactions, top by confidence:

A	B	Type	Score
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
COPS5	COPS6	psi-mi:“MI:0915”(physical association)	0.930
COPS6	COPS3	psi-mi:“MI:0915”(physical association)	0.920
COPS6	COPS4	psi-mi:“MI:0915”(physical association)	0.920
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
FBXO7	SKP1	psi-mi:“MI:0914”(association)	0.900
COPS6	COPS2	psi-mi:“MI:0914”(association)	0.880
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
COPS3	COPS2	psi-mi:“MI:0914”(association)	0.870
GPS1	COPS2	psi-mi:“MI:0915”(physical association)	0.860

BioGRID (761): COPS6 (Reconstituted Complex), NEDD8 (Reconstituted Complex), COPS6 (Co-crystal Structure), CDKN1B (Affinity Capture-Western), COPS6 (Affinity Capture-MS), COPS6 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), GPS1 (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CUL4A (Affinity Capture-MS), COPS4 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), DDB2 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A2AWA9, A2RSQ0, A6QQ21, A7TX81, B1H2N3, B5DGH9, B5KFI0, D2SW95, O43242, O88545, P11029, P11497, P14685, P17426, P23514, P53618, P60228, P60229, Q05AY2, Q07G98, Q0IIL1, Q13085, Q1LUA8, Q28559, Q2KJ46, Q3B8M3, Q3T102, Q4R518, Q4R6G8, Q5R8K9, Q5R8N4, Q5R922, Q5REY0, Q5SWU9, Q5ZIA5, Q5ZLA5, Q641X8, Q6DRI1, Q6NUC2

Diamond homologs: A1CQH7, A1D3E1, A2QQ10, A4R0E5, A5A6I3, A6QQ21, A7TX81, A8PZS4, B0XQ55, O00303, O43060, O88545, P0CO84, P0CO85, Q07G98, Q0CCM5, Q0UTQ6, Q1DRC9, Q2HGJ2, Q2UPM0, Q4PI88, Q4R5B8, Q4WTH0, Q54C49, Q5REY0, Q6C4H1, Q6NUC2, Q7L5N1, Q9DCH4, Q9P748, Q54C92, Q5BB47, Q6ZKM2, Q7S8C8, Q8W1P0, Q8W206, Q95PZ0, Q9VCY3, Q8WZY4, P68356

SIGNOR signaling

4 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
DNA Damage Recognition in GG-NER	12	35.3×	1e-13
RHOBTB1 GTPase cycle	6	29.4×	5e-06
Formation of TC-NER Pre-Incision Complex	12	26.2×	5e-12
Chaperone Mediated Autophagy	5	25.6×	1e-04
Iron uptake and transport	5	17.8×	6e-04
Neddylation	35	17.1×	1e-31
Late endosomal microautophagy	5	16.8×	7e-04
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	5	13.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	8	63.5×	5e-11
protein neddylation	9	53.6×	1e-11
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	10	31.7×	1e-10
intrinsic apoptotic signaling pathway	7	21.3×	5e-06
cellular response to UV	6	15.0×	3e-04
protein monoubiquitination	5	14.6×	2e-03
G1/S transition of mitotic cell cycle	7	11.9×	2e-04
protein ubiquitination	30	10.5×	2e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1157 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100089037:G:GT	donor_gain	1.0000
7:100089063:GCAG:G	donor_gain	1.0000
7:100089064:CAG:C	donor_loss	1.0000
7:100089067:G:GA	donor_loss	1.0000
7:100089282:A:AG	acceptor_gain	1.0000
7:100089288:A:AG	acceptor_gain	1.0000
7:100089289:G:GA	acceptor_gain	1.0000
7:100089289:GT:G	acceptor_gain	1.0000
7:100089289:GTA:G	acceptor_gain	1.0000
7:100089397:G:GT	donor_gain	1.0000
7:100089411:GCAGG:G	donor_gain	1.0000
7:100089412:CAGGG:C	donor_loss	1.0000
7:100089413:AGGG:A	donor_loss	1.0000
7:100089414:GG:G	donor_gain	1.0000
7:100089414:GGGTG:G	donor_loss	1.0000
7:100089415:GG:G	donor_gain	1.0000
7:100089416:G:GG	donor_gain	1.0000
7:100089613:A:AG	acceptor_gain	1.0000
7:100089613:AGT:A	acceptor_gain	1.0000
7:100089614:G:GG	acceptor_gain	1.0000
7:100089614:GT:G	acceptor_gain	1.0000
7:100089614:GTG:G	acceptor_gain	1.0000
7:100089614:GTGA:G	acceptor_gain	1.0000
7:100089695:G:GT	donor_gain	1.0000
7:100089719:G:GT	donor_gain	1.0000
7:100089720:A:T	donor_gain	1.0000
7:100089736:G:GT	donor_gain	1.0000
7:100089737:G:GT	donor_gain	1.0000
7:100089742:GCA:G	donor_gain	1.0000
7:100089745:G:GG	donor_gain	1.0000

AlphaMissense

2167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100089343:C:G	H44D	1.000
7:100089382:C:A	R57S	1.000
7:100089383:G:C	R57P	1.000
7:100089620:G:T	G70W	1.000
7:100089621:G:A	G70E	1.000
7:100089633:G:A	G74D	1.000
7:100089633:G:T	G74V	1.000
7:100089668:T:C	S86P	1.000
7:100089669:C:T	S86F	1.000
7:100090431:G:C	G123R	1.000
7:100090434:T:A	W124R	1.000
7:100090434:T:C	W124R	1.000
7:100090623:T:C	L152P	1.000
7:100091093:G:C	R197P	1.000
7:100091250:T:C	L221P	1.000
7:100091267:G:C	A227P	1.000
7:100091280:T:C	L231P	1.000
7:100089335:T:A	V41D	0.999
7:100089341:T:A	L43H	0.999
7:100089341:T:C	L43P	0.999
7:100089345:T:A	H44Q	0.999
7:100089345:T:G	H44Q	0.999
7:100089347:C:A	P45H	0.999
7:100089350:T:A	L46H	0.999
7:100089350:T:C	L46P	0.999
7:100089353:T:A	V47D	0.999
7:100089359:T:C	L49P	0.999
7:100089367:T:C	S52P	0.999
7:100089371:A:T	D53V	0.999
7:100089374:A:C	H54P	0.999

dbSNP variants (sampled 300 via entrez): RS1000138670 (7:100087543 T>A), RS1000377958 (7:100088036 A>G), RS1000687972 (7:100089004 C>T), RS1000915042 (7:100087614 G>T), RS1002466257 (7:100091860 TGA>T), RS1002701065 (7:100092157 C>G), RS1003206079 (7:100087373 A>T), RS1004253991 (7:100088691 A>G), RS1004605702 (7:100088910 G>C,T), RS1005198663 (7:100090804 T>G), RS1006252722 (7:100091921 C>G,T), RS1006279819 (7:100088846 G>A,C,T), RS1006414141 (7:100089016 C>T), RS1007419249 (7:100092062 C>G,T), RS1007824263 (7:100092602 C>G,T)

Disease associations

OMIM: gene MIM:614729 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067091 (SINGLE PROTEIN)

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

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	increases expression, affects cotreatment	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 expression, increases abundance	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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SJ52	HAP1 COPS6 (-) 1	Cancer cell line	Male
CVCL_SJ53	HAP1 COPS6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	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	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	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	PHASE4	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	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	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	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	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	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer