COPS8

Summary

COPS8 (COP9 signalosome subunit 8, HGNC:24335) is a protein-coding gene on chromosome 2q37.3, encoding COP9 signalosome complex subunit 8 (Q99627). 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 98.8% 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. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 10920 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 43 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24335
Approved symbol	COPS8
Name	COP9 signalosome subunit 8
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	COP9, CSN8, MGC1297, SGN8
Ensembl gene	ENSG00000198612
Ensembl biotype	protein_coding
OMIM	616011
Entrez	10920

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000354371, ENST00000392008, ENST00000409334, ENST00000419015, ENST00000447464, ENST00000465362, ENST00000470452, ENST00000855904, ENST00000855905, ENST00000855906, ENST00000930830

RefSeq mRNA: 2 — MANE Select: NM_006710 NM_006710, NM_198189

CCDS: CCDS2517, CCDS42835

Canonical transcript exons

ENST00000354371 — 8 exons

Exon	Start	End
ENSE00001142591	237096822	237096869
ENSE00001142598	237095822	237095884
ENSE00001142606	237094090	237094197
ENSE00001819930	237097663	237100474
ENSE00002311798	237085889	237086042
ENSE00003481991	237087127	237087197
ENSE00003546557	237089862	237089994
ENSE00003656173	237088605	237088653

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.8487 / max 265.6956, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26241	48.8487	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.87	gold quality
oocyte	CL:0000023	99.85	gold quality
endothelial cell	CL:0000115	99.39	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.44	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.42	gold quality
middle temporal gyrus	UBERON:0002771	98.34	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.29	gold quality
substantia nigra pars compacta	UBERON:0001965	98.24	gold quality
pons	UBERON:0000988	97.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.70	gold quality
lateral globus pallidus	UBERON:0002476	97.64	gold quality
dorsal root ganglion	UBERON:0000044	97.49	gold quality
superior vestibular nucleus	UBERON:0007227	97.41	gold quality
heart right ventricle	UBERON:0002080	97.39	gold quality
biceps brachii	UBERON:0001507	97.38	gold quality
decidua	UBERON:0002450	97.36	gold quality
gastrocnemius	UBERON:0001388	97.22	gold quality
choroid plexus epithelium	UBERON:0003911	97.22	gold quality
germinal epithelium of ovary	UBERON:0001304	97.21	gold quality
orbitofrontal cortex	UBERON:0004167	97.21	gold quality
cranial nerve II	UBERON:0000941	97.20	gold quality
trigeminal ganglion	UBERON:0001675	97.09	gold quality
ventral tegmental area	UBERON:0002691	97.05	gold quality
entorhinal cortex	UBERON:0002728	97.02	gold quality
CA1 field of hippocampus	UBERON:0003881	97.02	gold quality
pigmented layer of retina	UBERON:0001782	96.99	gold quality
adult organism	UBERON:0007023	96.92	gold quality
prefrontal cortex	UBERON:0000451	96.88	gold quality
muscle of leg	UBERON:0001383	96.85	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	533.43
E-MTAB-7303	no	293.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting COPS8, 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-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-26A-1-3P	99.64	66.81	788

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• DDB2 and CSA are each integrated into nearly identical complexes via interaction with DDB1. Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity. They also contain the COP9 signalosome (CSN) (PMID:12732143)
• The COP9 signalosome (CSN) controls NF-kappaB by deubiquitinylation of IkappaBalpha. (PMID:17318178)
• COP9/signalosome increases the efficiency of von Hippel-Lindau protein ubiquitin ligase-mediated hypoxia-inducible factor-alpha ubiquitination (PMID:18424433)
• analysis of the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3 (PMID:20399188)
• proteomic-based approach can broaden our understanding of the functions of the CSN in contexts such as viral-host interactions or immune activation in their natural milieu (PMID:22414063)
• miR-146a expression is up-regulated in a majority of gastric cancers where it targets CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB. (PMID:22992343)
• Data indicate that silencing of Csn8 caused an increased growth rate, whereas silencing of Csn5 impaired proliferation in HeLa cells. (PMID:23689509)
• Among 479 individuals affected with clear cell renal cell carcinoma, only synonymous variants were found in COPS8 and one of the missense variants in ACKR3:c.892C>T, was observed in 4/479 individuals screened (PMID:28063109)
• CSN8 is a key regulator in hypoxia-induced epithelial-mesenchymal transition and dormancy of colorectal cancer cells. (PMID:33261601)
• COPS8 in cutaneous melanoma: an oncogene that accelerates the malignant development of tumor cells and predicts poor prognosis. (PMID:33604618)
• COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma. (PMID:38466642)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cops8	ENSMUSG00000034432
rattus_norvegicus	Cops8	ENSRNOG00000019635

Protein

Protein identifiers

COP9 signalosome complex subunit 8 — Q99627 (reviewed: Q99627)

Alternative names: COP9 homolog, JAB1-containing signalosome subunit 8

All UniProt accessions (4): E9PGT6, Q99627, F8WEF2, H7C3S9

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/ICSBP, 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.

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 COPS3, COPS4 and COPS7 (COPS7A or COPS7B).

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the CSN8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99627-1	1	yes
Q99627-2	2

RefSeq proteins (2): NP_006701, NP_937832 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR033205	COP9_CSN8	Family
IPR033464	CSN8_PSD8_EIF3K	Domain

Pfam: PF10075

UniProt features (5 total): initiator methionine 1, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
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
6R7N	ELECTRON MICROSCOPY	6.5
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-Q99627-F1	85.78	0.73

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 175

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: 180 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GOBP_PROTEIN_NEDDYLATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, ONKEN_UVEAL_MELANOMA_UP, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (7): protein deneddylation (GO:0000338), protein phosphorylation (GO:0006468), activation of NF-kappaB-inducing kinase activity (GO:0007250), negative regulation of cell population proliferation (GO:0008285), COP9 signalosome assembly (GO:0010387), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434)

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

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), COP9 signalosome (GO:0008180), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), protein-containing complex (GO:0032991)

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
phosphorylation	1
protein modification process	1
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
protein-containing complex assembly	1
protein modification by small protein conjugation	1
protein neddylation	1
regulation of protein modification by small protein conjugation or removal	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
extracellular vesicle	1
cellular_component	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS8	COPS4	Q9BT78	986
COPS8	COPS7A	Q9UBW8	976
COPS8	COPS6	Q7L5N1	950
COPS8	COPS5	Q92905	931
COPS8	GPS1	Q13098	893
COPS8	COPS7B	Q9H9Q2	853
COPS8	CUL4A	Q13619	833
COPS8	COPS2	P61201	811
COPS8	RBX1	P62877	799
COPS8	COPS3	Q9UNS2	776
COPS8	NEDD8	Q15843	735
COPS8	COPS9	Q8WXC6	700
COPS8	C5orf34	Q96MH7	684
COPS8	CUL3	Q13618	680
COPS8	CCDC124	Q96CT7	665

IntAct

171 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
COPS8	COPS3	psi-mi:“MI:0915”(physical association)	0.940
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
COPS6	COPS2	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
COPS8	COPS2	psi-mi:“MI:0914”(association)	0.850
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790

BioGRID (299): USHBP1 (Two-hybrid), COPS8 (Affinity Capture-Western), COPS8 (Affinity Capture-Western), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), COPS8 (Co-fractionation), COPS8 (Co-fractionation), COPS8 (Co-fractionation), COPS8 (Co-fractionation), COPS8 (Co-fractionation)

ESM2 similar proteins: A7Y521, B0BN93, B5DGH9, F1LMZ8, F1QGH9, F6P3G4, F6XBL2, O00231, O35142, O43242, O55029, O88544, P14685, P35605, P35606, P60228, P60229, P84169, Q05AY2, Q13098, Q1LUA8, Q2KI42, Q2KJ46, Q3B8M3, Q3SZA0, Q3T102, Q4R5E6, Q4R6G8, Q5E964, Q5R648, Q5R664, Q5R8K9, Q5RF54, Q5ZLA5, Q641X8, Q68FS2, Q6DRI1, Q6NRT5, Q6P0H6, Q6P4Z9

Diamond homologs: P43255, P68396, Q5RF54, Q6GQA6, Q6P4Z9, Q6P637, Q7ZUZ0, Q8VBV7, Q99627, Q75K24

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
COPS8	“form complex”	“COP9 signalosome variant 2”	binding
COPS8	“form complex”	“COP9 signalosome variant 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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	38.1×	3e-14
RHOBTB1 GTPase cycle	5	26.4×	9e-05
Formation of TC-NER Pre-Incision Complex	11	25.9×	5e-11
Recognition of DNA damage by PCNA-containing replication complex	5	21.1×	3e-04
Neddylation	31	16.3×	4e-27
Dual Incision in GG-NER	5	14.4×	2e-03
Formation of Incision Complex in GG-NER	5	14.1×	2e-03
Activation of NF-kappaB in B cells	5	10.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	8	71.3×	2e-11
protein neddylation	9	60.2×	5e-12
intrinsic apoptotic signaling pathway	6	20.5×	5e-05
cellular response to UV	5	14.1×	2e-03
positive regulation of protein catabolic process	6	11.6×	1e-03
G1/S transition of mitotic cell cycle	6	11.5×	1e-03
protein ubiquitination	26	10.2×	2e-16
ubiquitin-dependent protein catabolic process	14	9.9×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1312 predictions. Top by Δscore:

Variant	Effect	Δscore
2:237088589:T:TA	acceptor_gain	1.0000
2:237096820:A:AG	acceptor_gain	1.0000
2:237096821:G:GG	acceptor_gain	1.0000
2:237096821:GTT:G	acceptor_gain	1.0000
2:237097661:A:AG	acceptor_gain	1.0000
2:237097662:G:GG	acceptor_gain	1.0000
2:237086797:G:GG	donor_gain	0.9900
2:237087116:T:A	acceptor_gain	0.9900
2:237087198:G:GG	donor_gain	0.9900
2:237088587:T:TA	acceptor_gain	0.9900
2:237088590:G:A	acceptor_gain	0.9900
2:237088592:T:TA	acceptor_gain	0.9900
2:237088649:AATCT:A	donor_gain	0.9900
2:237088654:G:GG	donor_gain	0.9900
2:237094077:A:AG	acceptor_gain	0.9900
2:237094085:A:AG	acceptor_gain	0.9900
2:237094086:ATAG:A	acceptor_loss	0.9900
2:237094088:A:AG	acceptor_gain	0.9900
2:237094088:A:T	acceptor_loss	0.9900
2:237094089:G:GG	acceptor_gain	0.9900
2:237094194:AAAGG:A	donor_loss	0.9900
2:237094195:AAG:A	donor_loss	0.9900
2:237094197:GGT:G	donor_loss	0.9900
2:237094198:GTA:G	donor_loss	0.9900
2:237094199:T:A	donor_loss	0.9900
2:237095816:TTTTA:T	acceptor_loss	0.9900
2:237095819:TA:T	acceptor_loss	0.9900
2:237095820:A:AG	acceptor_gain	0.9900
2:237095820:AGG:A	acceptor_loss	0.9900
2:237095821:G:GG	acceptor_gain	0.9900

AlphaMissense

1352 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:237088622:T:C	L56P	1.000
2:237094120:T:A	V121D	1.000
2:237095839:T:A	W153R	1.000
2:237095839:T:C	W153R	1.000
2:237097711:T:C	L200P	1.000
2:237097728:T:C	F206L	1.000
2:237097730:C:A	F206L	1.000
2:237097730:C:G	F206L	1.000
2:237097732:T:A	L207H	1.000
2:237097732:T:C	L207P	1.000
2:237087167:T:C	L40P	0.999
2:237088613:C:A	A53E	0.999
2:237088616:G:C	R54T	0.999
2:237088617:A:C	R54S	0.999
2:237088617:A:T	R54S	0.999
2:237088631:G:C	R59T	0.999
2:237088632:A:C	R59S	0.999
2:237088632:A:T	R59S	0.999
2:237088634:T:A	I60K	0.999
2:237089886:T:A	W75R	0.999
2:237089886:T:C	W75R	0.999
2:237089895:G:A	G78R	0.999
2:237089895:G:C	G78R	0.999
2:237089896:G:A	G78E	0.999
2:237089955:T:A	W98R	0.999
2:237089955:T:C	W98R	0.999
2:237094117:T:C	L120P	0.999
2:237094131:T:G	Y125D	0.999
2:237094137:T:C	S127P	0.999
2:237094141:T:A	I128N	0.999

dbSNP variants (sampled 300 via entrez): RS1000053513 (2:237094344 T>C), RS1000130283 (2:237098110 T>A), RS1000172172 (2:237085550 G>C), RS1000455492 (2:237097560 C>T), RS1000461488 (2:237097781 G>A,C,T), RS1000680888 (2:237086985 A>G), RS1000729023 (2:237091489 T>C), RS1000749993 (2:237085875 C>A,T), RS1001099946 (2:237086795 T>C), RS1001109361 (2:237087327 G>A), RS1001293311 (2:237100783 ATATATATATATGTG>A), RS1001580843 (2:237100877 A>C,G), RS1001772035 (2:237084458 G>C,T), RS1002155670 (2:237096021 G>A), RS1002524557 (2:237099756 T>C)

Disease associations

OMIM: gene MIM:616011 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002759_15	Motion sickness	3.000000e-12
GCST002783_449	Body mass index	8.000000e-06
GCST003831_38	Asthma	8.000000e-06
GCST004748_77	Lung cancer	7.000000e-06
GCST004867_24	Systemic lupus erythematosus	3.000000e-06
GCST007096_206	Pulse pressure	5.000000e-08
GCST010866_5	Coronary artery disease	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296015 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.81	Kd	1543	nM	CHEMBL5653589
5.81	ED50	1544	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	2148124: Binding affinity to human COPS8 incubated for 45 mins by Kinobead based pull down assay	kd	1.5432	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases expression, affects expression	2
Aflatoxin B1	increases expression, increases methylation	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
cupric chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Phthalic Acids	increases methylation	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Antirheumatic Agents	increases expression	1
beta-Naphthoflavone	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118623	Binding	Binding affinity to COPS8 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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