COPS3

Summary

COPS3 (COP9 signalosome subunit 3, HGNC:2239) is a protein-coding gene on chromosome 17p11.2, encoding COP9 signalosome complex subunit 3 (Q9UNS2). Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.

The protein encoded by this gene possesses kinase activity that phosphorylates regulators involved in signal transduction. It phosphorylates I kappa-Balpha, p105, and c-Jun. It acts as a docking site for complex-mediated phosphorylation. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8533 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 79 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_003653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2239
Approved symbol	COPS3
Name	COP9 signalosome subunit 3
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	SGN3, CSN3
Ensembl gene	ENSG00000141030
Ensembl biotype	protein_coding
OMIM	604665
Entrez	8533

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 21 protein_coding, 7 nonsense_mediated_decay, 5 retained_intron

ENST00000268717, ENST00000417352, ENST00000439936, ENST00000462236, ENST00000463097, ENST00000471414, ENST00000477299, ENST00000486032, ENST00000486810, ENST00000492672, ENST00000495640, ENST00000539941, ENST00000577210, ENST00000577246, ENST00000578317, ENST00000579716, ENST00000583160, ENST00000584216, ENST00000904391, ENST00000904392, ENST00000904393, ENST00000904394, ENST00000904395, ENST00000904396, ENST00000904397, ENST00000938830, ENST00000938831, ENST00000938832, ENST00000938833, ENST00000938834, ENST00000954594, ENST00000954595, ENST00000954596

RefSeq mRNA: 7 — MANE Select: NM_003653 NM_001199125, NM_001316354, NM_001316355, NM_001316356, NM_001316357, NM_001316358, NM_003653

CCDS: CCDS11183, CCDS56022

Canonical transcript exons

ENST00000268717 — 12 exons

Exon	Start	End
ENSE00001901824	17281132	17281246
ENSE00002721947	17246616	17247151
ENSE00003458989	17248926	17249039
ENSE00003475753	17270758	17270807
ENSE00003519143	17260301	17260474
ENSE00003581107	17276035	17276164
ENSE00003582176	17270896	17271008
ENSE00003592268	17247480	17247560
ENSE00003624911	17264802	17264981
ENSE00003635224	17254859	17254945
ENSE00003671261	17267885	17267977
ENSE00003788263	17261966	17262106

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.9489 / max 768.2898, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164758	21.4143	1810
164759	9.6144	1773
164760	9.6095	1772
164757	7.3107	1697

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	97.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.65	gold quality
muscle of leg	UBERON:0001383	97.55	gold quality
cortical plate	UBERON:0005343	97.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.27	gold quality
muscle organ	UBERON:0001630	97.14	gold quality
skeletal muscle organ	UBERON:0014892	97.14	gold quality
ganglionic eminence	UBERON:0004023	97.07	gold quality
right testis	UBERON:0004534	97.07	gold quality
left testis	UBERON:0004533	97.05	gold quality
testis	UBERON:0000473	96.52	gold quality
skeletal muscle tissue	UBERON:0001134	96.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.09	gold quality
vastus lateralis	UBERON:0001379	96.08	gold quality
biceps brachii	UBERON:0001507	96.01	gold quality
quadriceps femoris	UBERON:0001377	95.96	gold quality
triceps brachii	UBERON:0001509	95.81	gold quality
islet of Langerhans	UBERON:0000006	95.74	gold quality
deltoid	UBERON:0001476	95.64	gold quality
monocyte	CL:0000576	95.52	gold quality
ventricular zone	UBERON:0003053	95.52	gold quality
gluteal muscle	UBERON:0002000	95.46	gold quality
mononuclear cell	CL:0000842	95.25	gold quality
leukocyte	CL:0000738	95.21	gold quality
heart left ventricle	UBERON:0002084	95.19	gold quality
bone marrow	UBERON:0002371	95.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.14	gold quality
prefrontal cortex	UBERON:0000451	95.06	gold quality
cardiac ventricle	UBERON:0002082	95.04	gold quality
adenohypophysis	UBERON:0002196	95.04	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	465.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

54 targeting COPS3, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-5700	99.64	69.88	2280

Literature-anchored findings (GeneRIF, showing 7)

• of the COPS3 gene might have important roles in metastasis of osteosarcoma cells. (PMID:21436869)
• this study demonstrates Csn3 as an oncogene that regulates the tumorigenesis process in hepatocellular carcinoma (HCC) cells. (PMID:22237956)
• Here the authors identify a potential mechanism by which desmosomes assist the de-neddylating COP9 signalosome (CSN) in attenuating EGFR through an association between the Cops3 subunit of the CSN and desmosomal components, Desmoglein1 (Dsg1) and Desmoplakin (Dp), to promote epidermal differentiation. (PMID:28891468)
• COPS3 may be a new potential target of clear cell renal cell carcinoma. (PMID:29477618)
• these data reveal a novel function of COPS3 in the regulation of autophagy and highlight the relationship between autophagy and metastasis in osteosarcoma cells. (PMID:29970115)
• COPS3 may be closely related to the progress of PCa. Knockdown of COPS3 inhibited the progress of PCa through reducing the levels of phosphorylated P38 MAPK and impaired the epithelial-mesenchymal transition process. (PMID:31509289)
• The COPS3-FOXO3 positive feedback loop regulates autophagy to promote cisplatin resistance in osteosarcoma. (PMID:36451342)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops3	ENSDARG00000008623
mus_musculus	Cops3	ENSMUSG00000019373
rattus_norvegicus	Cops3	ENSRNOG00000053943
drosophila_melanogaster	CSN3	FBGN0027055
caenorhabditis_elegans		WBGENE00004460

Paralogs (1): PSMD3 (ENSG00000108344)

Protein

Protein identifiers

COP9 signalosome complex subunit 3 — Q9UNS2 (reviewed: Q9UNS2)

Alternative names: JAB1-containing signalosome subunit 3

All UniProt accessions (10): C9JLV5, Q9UNS2, H7C3P9, J3KTQ1, J3QKR0, J3QL22, J3QS85, K7EJF9, K7ELN6, K7ES36

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 COPS1, COPS4, COPS8 and COPS9 isoform 1. Interacts with CK2 and PKD. Interacts with the translation initiation factor EIF3S6 and IKBKG. Interacts with ERCC6.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed. Expressed at high level in heart and skeletal muscle.

Miscellaneous. Amplified and overexpressed in some osteosarcomas (OS), suggesting that it may participate in TP53 degradation in OS.

Similarity. Belongs to the CSN3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNS2-1	1	yes
Q9UNS2-2	2

RefSeq proteins (7): NP_001186054, NP_001303283, NP_001303284, NP_001303285, NP_001303286, NP_001303287, NP_003644* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR048621	CSN3_C	Domain
IPR050756	CSN3	Family
IPR055089	COP9_N	Domain

Pfam: PF01399, PF21215, PF22788

UniProt features (9 total): modified residue 4, initiator methionine 1, chain 1, domain 1, region of interest 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-Q9UNS2-F1	84.64	0.51

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 (4): 2, 407, 410, 423

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: 278 (showing top): MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, PAL_PRMT5_TARGETS_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_PROTEIN_NEDDYLATION, REACTOME_MEMBRANE_TRAFFICKING, MODULE_16, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, chr4q13, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (8): protein deneddylation (GO:0000338), in utero embryonic development (GO:0001701), ubiquitin-dependent protein catabolic process (GO:0006511), signal transduction (GO:0007165), response to light stimulus (GO:0009416), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434)

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

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), COP9 signalosome (GO:0008180), perinuclear region of cytoplasm (GO:0048471), 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
chordate embryonic development	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to radiation	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of cellular response to stress	1
regulation of signal transduction by p53 class mediator	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
cellular_component	1

Protein interactions and networks

STRING

1708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS3	COPS2	P61201	981
COPS3	GPS1	Q13098	961
COPS3	COPS5	Q92905	899
COPS3	NT5M	Q9NPB1	893
COPS3	COPS6	Q7L5N1	874
COPS3	COPS4	Q9BT78	865
COPS3	COPS8	Q99627	776
COPS3	COPS7B	Q9H9Q2	775
COPS3	COPS7A	Q9UBW8	768
COPS3	LLGL1	Q15334	691
COPS3	DSP	P15924	567
COPS3	MED9	Q9NWA0	474
COPS3	NFKBIA	P25963	460
COPS3	JUN	P05412	454
COPS3	WDR77	Q9BQA1	451

IntAct

379 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
COPS3	COPS5	psi-mi:“MI:0915”(physical association)	0.930
COPS6	COPS3	psi-mi:“MI:0915”(physical association)	0.920
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
COPS3	COPS7A	psi-mi:“MI:0915”(physical association)	0.900
FBXO7	SKP1	psi-mi:“MI:0914”(association)	0.900
COPS6	COPS2	psi-mi:“MI:0914”(association)	0.880
COPS3	COPS2	psi-mi:“MI:0914”(association)	0.870
COPS3	COPS2	psi-mi:“MI:0915”(physical association)	0.870
GPS1	COPS2	psi-mi:“MI:0915”(physical association)	0.860

BioGRID (517): COPS3 (Affinity Capture-Western), COPS3 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), COPS3 (Affinity Capture-MS), MYEOV2 (Affinity Capture-MS), COPS8 (Affinity Capture-MS), DCAF4 (Affinity Capture-MS), GPS1 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CUL4A (Affinity Capture-MS), COPS4 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), COPS7B (Affinity Capture-MS)

ESM2 similar proteins: A6H7B5, A7SPX9, B0WTN3, B3MCZ5, B3NRC6, B4GDM5, B4HR14, B4JW83, B4KT65, B4LJT9, B4MY75, B4P6M6, B4QFD2, O13873, O88543, Q0U0X1, Q10335, Q12377, Q17D30, Q28IV6, Q292F0, Q2HBQ2, Q2TBN6, Q3SYT7, Q4R898, Q54B82, Q54E53, Q54NQ0, Q55C75, Q5DHT6, Q5FWP8, Q5JVF3, Q5RE15, Q5RFS2, Q5U3P0, Q5ZJF1, Q68FW9, Q6P2U9, Q7JVI3, Q7Q068

Diamond homologs: A6H7B5, O88543, P68358, Q28IV6, Q4R898, Q54E53, Q5RFS2, Q5ZJF1, Q68FW9, Q6P2U9, Q7ZTN8, Q8SYG2, Q8W575, Q9UNS2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MLF1	up-regulates	COPS3	binding
COPS3	“up-regulates quantity by stabilization”	SOS1	binding
COPS3	“form complex”	“COP9 signalosome variant 2”	binding
COPS3	“form complex”	“COP9 signalosome variant 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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	10	31.7×	1e-10
Formation of TC-NER Pre-Incision Complex	10	23.5×	2e-09
Neddylation	26	13.7×	4e-20
Cargo recognition for clathrin-mediated endocytosis	9	10.5×	2e-05
Antigen processing: Ubiquitination & Proteasome degradation	15	6.2×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	8	68.7×	4e-11
protein neddylation	9	58.0×	9e-12
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	8	27.5×	9e-08
intrinsic apoptotic signaling pathway	6	19.7×	9e-05
G1/S transition of mitotic cell cycle	6	11.0×	2e-03
protein autoubiquitination	5	10.7×	7e-03
protein polyubiquitination	7	7.4×	4e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	15	7.2×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	55
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57091	GRCh38/hg38 4q13.2-13.3(chr4:66842408-70831557)x1	Pathogenic

SpliceAI

1906 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17247148:TACT:T	acceptor_gain	1.0000
17:17247150:CT:C	acceptor_gain	1.0000
17:17247152:C:CC	acceptor_gain	1.0000
17:17247476:TCA:T	donor_loss	1.0000
17:17247479:C:CA	donor_loss	1.0000
17:17247491:A:AC	donor_gain	1.0000
17:17247492:C:CC	donor_gain	1.0000
17:17247559:ATC:A	acceptor_loss	1.0000
17:17247561:C:CC	acceptor_gain	1.0000
17:17247562:T:C	acceptor_loss	1.0000
17:17248921:TTTAC:T	donor_loss	1.0000
17:17248923:TACCT:T	donor_loss	1.0000
17:17248924:ACC:A	donor_loss	1.0000
17:17248924:ACCT:A	donor_gain	1.0000
17:17248925:CCTC:C	donor_gain	1.0000
17:17248927:T:TA	donor_gain	1.0000
17:17249036:CTAT:C	acceptor_gain	1.0000
17:17249037:TAT:T	acceptor_gain	1.0000
17:17249037:TATC:T	acceptor_loss	1.0000
17:17249038:AT:A	acceptor_gain	1.0000
17:17249038:ATCT:A	acceptor_loss	1.0000
17:17249040:C:CC	acceptor_gain	1.0000
17:17249040:CT:C	acceptor_loss	1.0000
17:17260294:T:A	donor_gain	1.0000
17:17260475:C:CC	acceptor_gain	1.0000
17:17264977:CAAAG:C	acceptor_gain	1.0000
17:17267978:C:CC	acceptor_gain	1.0000
17:17268044:CACT:C	acceptor_gain	1.0000
17:17268047:T:C	acceptor_gain	1.0000
17:17268047:T:TC	acceptor_gain	1.0000

AlphaMissense

2808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17248983:G:C	F360L	1.000
17:17248983:G:T	F360L	1.000
17:17248984:A:C	F360C	1.000
17:17248984:A:G	F360S	1.000
17:17248985:A:G	F360L	1.000
17:17248990:A:T	V358D	1.000
17:17249011:A:C	I351S	1.000
17:17249011:A:T	I351N	1.000
17:17249017:G:T	A349E	1.000
17:17254859:C:A	M341I	1.000
17:17254859:C:G	M341I	1.000
17:17254859:C:T	M341I	1.000
17:17254869:A:T	V338D	1.000
17:17254882:C:G	A334P	1.000
17:17254915:C:G	A323P	1.000
17:17254932:A:G	L317P	1.000
17:17254932:A:T	L317Q	1.000
17:17254940:A:C	F314L	1.000
17:17254940:A:T	F314L	1.000
17:17254941:A:G	F314S	1.000
17:17254942:A:G	F314L	1.000
17:17254942:A:T	F314I	1.000
17:17260308:A:G	L310P	1.000
17:17262077:A:C	S217R	1.000
17:17262077:A:T	S217R	1.000
17:17262079:T:G	S217R	1.000
17:17262090:G:T	A213D	1.000
17:17264857:C:T	G189E	1.000
17:17264858:C:A	G189W	1.000
17:17264858:C:G	G189R	1.000

dbSNP variants (sampled 300 via entrez): RS1000022699 (17:17279982 T>C), RS1000181907 (17:17249486 G>C,T), RS1000292884 (17:17276413 C>T), RS1000385602 (17:17255237 T>C), RS1000406382 (17:17276130 C>G), RS1000452656 (17:17281672 G>A), RS1000502229 (17:17270419 T>C), RS1000519228 (17:17247978 G>A,T), RS1000689304 (17:17252385 T>C), RS1000761082 (17:17281967 C>T), RS1000825008 (17:17252222 T>C), RS1000886258 (17:17259034 G>A,T), RS1000895744 (17:17265729 A>G), RS1000938322 (17:17246685 A>C,G), RS1000990154 (17:17265393 A>C,T)

Disease associations

OMIM: gene MIM:604665 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST90002392_7	Mean corpuscular volume	9.000000e-12
GCST90002397_732	Mean spheric corpuscular volume	7.000000e-18
GCST90002399_283	Neutrophil percentage of white cells	3.000000e-09
GCST90002405_329	Reticulocyte count	1.000000e-09
GCST90011898_49	Alanine aminotransferase levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066248 (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
6.96	Kd	109.2	nM	CHEMBL5653589
6.96	ED50	109.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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	2148121: Binding affinity to human COPS3 incubated for 45 mins by Kinobead based pull down assay	kd	0.1092	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases palmitoylation, decreases expression, decreases reaction	3
bisphenol A	decreases methylation, decreases expression	2
Cadmium	decreases expression, decreases reaction, increases abundance, increases palmitoylation	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
tetrahydropalmatine	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Calcium Chloride	increases expression	1
Cisplatin	increases expression	1
Clozapine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Doxorubicin	affects expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Haloperidol	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases 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
CHEMBL5651163	Binding	Binding affinity to human COPS3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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