COPS7A

Summary

COPS7A (COP9 signalosome subunit 7A, HGNC:16758) is a protein-coding gene on chromosome 12p13.31, encoding COP9 signalosome complex subunit 7a (Q9UBW8). Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.

This gene encodes a component of the COP9 signalosome, an evolutionarily conserved multi-subunit protease that regulates the activity of the ubiquitin conjugation pathway. Alternatively spliced transcript variants that encode the same protein have been described.

Source: NCBI Gene 50813 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_001164094

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16758
Approved symbol	COPS7A
Name	COP9 signalosome subunit 7A
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	CSN7A
Ensembl gene	ENSG00000111652
Ensembl biotype	protein_coding
OMIM	616009
Entrez	50813

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 40 protein_coding, 10 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000229251, ENST00000455113, ENST00000534877, ENST00000534947, ENST00000536872, ENST00000537022, ENST00000538375, ENST00000538410, ENST00000538753, ENST00000539735, ENST00000540408, ENST00000541866, ENST00000542150, ENST00000542630, ENST00000543155, ENST00000543170, ENST00000543537, ENST00000543939, ENST00000544316, ENST00000544725, ENST00000546229, ENST00000889557, ENST00000889558, ENST00000889559, ENST00000889560, ENST00000889561, ENST00000889562, ENST00000889563, ENST00000889564, ENST00000889565, ENST00000889566, ENST00000889567, ENST00000889568, ENST00000889569, ENST00000889570, ENST00000889571, ENST00000889572, ENST00000889573, ENST00000928876, ENST00000928877, ENST00000928878, ENST00000928879, ENST00000928880, ENST00000928881, ENST00000928882, ENST00000928883, ENST00000956855, ENST00000956856, ENST00000956857, ENST00000956858, ENST00000956859, ENST00000956860

RefSeq mRNA: 4 — MANE Select: NM_001164094 NM_001164093, NM_001164094, NM_001164095, NM_016319

CCDS: CCDS8558

Canonical transcript exons

ENST00000543155 — 8 exons

Exon	Start	End
ENSE00001768170	6731000	6731865
ENSE00002238006	6724046	6724179
ENSE00003433080	6724614	6724818
ENSE00003470204	6727926	6728001
ENSE00003614193	6730402	6730507
ENSE00003660227	6730669	6730820
ENSE00003670235	6729247	6729449
ENSE00003693806	6728223	6728311

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8673 / max 126.6371, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123712	14.7798	1789
123709	11.1128	1778
123714	3.6778	1535
123713	1.7361	1166
123711	0.7959	556
123710	0.7648	543

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	97.25	gold quality
stromal cell of endometrium	CL:0002255	97.18	gold quality
right frontal lobe	UBERON:0002810	96.70	gold quality
cingulate cortex	UBERON:0003027	96.15	gold quality
anterior cingulate cortex	UBERON:0009835	96.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.04	gold quality
apex of heart	UBERON:0002098	95.97	gold quality
right adrenal gland	UBERON:0001233	95.95	gold quality
right adrenal gland cortex	UBERON:0035827	95.92	gold quality
gastrocnemius	UBERON:0001388	95.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.66	gold quality
muscle of leg	UBERON:0001383	95.65	gold quality
amygdala	UBERON:0001876	95.55	gold quality
adenohypophysis	UBERON:0002196	95.49	gold quality
right atrium auricular region	UBERON:0006631	95.49	gold quality
thoracic aorta	UBERON:0001515	95.44	gold quality
left adrenal gland	UBERON:0001234	95.42	gold quality
ascending aorta	UBERON:0001496	95.41	gold quality
heart left ventricle	UBERON:0002084	95.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.36	gold quality
left coronary artery	UBERON:0001626	95.32	gold quality
descending thoracic aorta	UBERON:0002345	95.32	gold quality
pons	UBERON:0000988	95.28	gold quality
frontal cortex	UBERON:0001870	95.28	gold quality
frontal lobe	UBERON:0016525	95.28	gold quality
right coronary artery	UBERON:0001625	95.22	gold quality
left adrenal gland cortex	UBERON:0035825	95.20	gold quality
cardiac ventricle	UBERON:0002082	95.18	gold quality
cerebellar hemisphere	UBERON:0002245	95.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.64
E-GEOD-100618	no	607.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting COPS7A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4688	99.48	64.68	828

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops7a	ENSDARG00000022788
mus_musculus	Cops7a	ENSMUSG00000030127
rattus_norvegicus	Cops7a	ENSRNOG00000016778
drosophila_melanogaster	CSN7	FBGN0028836

Paralogs (2): COPS7B (ENSG00000144524), EIF3M (ENSG00000149100)

Protein

Protein identifiers

COP9 signalosome complex subunit 7a — Q9UBW8 (reviewed: Q9UBW8)

Alternative names: Dermal papilla-derived protein 10, JAB1-containing signalosome subunit 7a

All UniProt accessions (9): Q9UBW8, F5GXT7, F5GYF7, F5H248, F5H3M6, F5H4U8, F5H4Z0, F5H7C6, G3XAP1

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, JUN, I-kappa-B-alpha/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, COPS2, COPS4, COPS5, COPS6 and COPS8. Interacts with PMF1. Interacts with the translation initiation factor EIF3S6. Interacts with CK2 and PKD. Interacts directly with ID3. (Microbial infection) Interacts with vaccinia virus protein C9L.

Subcellular location. Cytoplasm. Nucleus.

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

Post-translational modifications. Phosphorylated by CK2 and PKD kinases.

Similarity. Belongs to the CSN7/EIF3M family. CSN7 subfamily.

RefSeq proteins (4): NP_001157565, NP_001157566, NP_001157567, NP_057403 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR041481	CSN7_helixI	Domain
IPR045237	COPS7/eIF3m	Family

Pfam: PF01399, PF18392, PF22061

UniProt features (10 total): compositionally biased region 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1, region of interest 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4D10	X-RAY DIFFRACTION	3.8
4D18	X-RAY DIFFRACTION	4.08
4WSN	X-RAY DIFFRACTION	5.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBW8-F1	84.98	0.72

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): 2

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: 184 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PROTEIN_NEDDYLATION, KYNG_DNA_DAMAGE_DN, TGACCTY_ERR1_Q2, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GCM_DDX11, ELK1_01, CCCAGAG_MIR326, REACTOME_DNA_REPAIR, TAATTA_CHX10_01

GO Biological Process (4): protein deneddylation (GO:0000338), 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 (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), COP9 signalosome (GO:0008180), 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	3
protein modification by small protein removal	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
cytoplasm	1
nuclear protein-containing complex	1
cellular_component	1

Protein interactions and networks

STRING

1005 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS7A	COPS8	Q99627	976
COPS7A	COPS4	Q9BT78	973
COPS7A	COPS6	Q7L5N1	946
COPS7A	COPS5	Q92905	927
COPS7A	GHITM	Q9H3K2	877
COPS7A	COPS2	P61201	815
COPS7A	GPS1	Q13098	795
COPS7A	MINDY3	Q9H8M7	771
COPS7A	COPS3	Q9UNS2	768
COPS7A	TMEM45A	Q9NWC5	714
COPS7A	NEDD8	Q15843	687
COPS7A	EIF3H	O15372	619
COPS7A	ROGDI	Q9GZN7	618
COPS7A	DCAF5	Q96JK2	594
COPS7A	PEDS1	A5PLL7	583

IntAct

203 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	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
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
COPS2	GPS1	psi-mi:“MI:0914”(association)	0.860

BioGRID (357): PTGS2 (Reconstituted Complex), COPS7A (Two-hybrid), COPS7A (Affinity Capture-MS), COPS7A (Affinity Capture-MS), COPS7A (Affinity Capture-MS), COPS7A (Affinity Capture-MS), COPS7A (Affinity Capture-MS), COPS7A (Affinity Capture-MS), ARHGEF2 (Co-fractionation), COPS2 (Co-fractionation), COPS3 (Co-fractionation), COPS4 (Co-fractionation), COPS5 (Co-fractionation), COPS6 (Co-fractionation), COPS7A (Co-fractionation)

ESM2 similar proteins: A4FV58, A5GFZ6, A6H791, A6H7F2, D3ZAA9, D4A1R8, D4A7C0, E7F3I6, H1UBN0, O88618, P49004, Q02053, Q08DB4, Q4IQT8, Q4PF70, Q4QR99, Q4R4J2, Q4R579, Q4WT40, Q56XY2, Q58DD9, Q5BJ53, Q5E9M9, Q5R762, Q5RF36, Q5U300, Q5ZKI2, Q66JK4, Q66KF6, Q6NS21, Q6PUR6, Q7TMW6, Q7TSA0, Q7YRA3, Q86U10, Q8C166, Q8CHW4, Q8IXI1, Q8JZN7, Q8VEJ1

Diamond homologs: Q2KI56, Q55BD5, Q5R762, Q7SGS1, Q8BV13, Q94JU3, Q9CZ04, Q9H9Q2, Q9UBW8, Q9V4S8, Q00648, B4GDM5, B4JW83, B4KT65, P68395, Q0CPV5, Q292F0, Q2UDZ9, A8WQY8, Q94261

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COPS7A	“form complex”	“COP9 signalosome variant 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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	32.0×	4e-13
Formation of TC-NER Pre-Incision Complex	12	23.7×	1e-11
RHOBTB1 GTPase cycle	5	22.2×	3e-04
Recognition of DNA damage by PCNA-containing replication complex	5	17.8×	7e-04
Neddylation	37	16.4×	9e-33
Iron uptake and transport	5	16.2×	1e-03
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	5	12.4×	3e-03
Dual Incision in GG-NER	5	12.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	8	53.5×	2e-10
protein neddylation	9	45.1×	8e-11
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	9	24.1×	2e-08
intrinsic apoptotic signaling pathway	7	17.9×	1e-05
protein monoubiquitination	6	14.7×	3e-04
cellular response to UV	5	10.6×	6e-03
protein ubiquitination	35	10.3×	6e-23
G1/S transition of mitotic cell cycle	7	10.0×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1397 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6724816:GAG:G	donor_gain	1.0000
12:6724816:GAGG:G	donor_loss	1.0000
12:6724817:AGGT:A	donor_loss	1.0000
12:6724818:GGT:G	donor_loss	1.0000
12:6724819:G:T	donor_loss	1.0000
12:6724820:T:G	donor_loss	1.0000
12:6728210:C:A	acceptor_gain	1.0000
12:6728218:CCTA:C	acceptor_loss	1.0000
12:6728220:TA:T	acceptor_loss	1.0000
12:6728221:A:AG	acceptor_gain	1.0000
12:6728221:AGCT:A	acceptor_gain	1.0000
12:6728222:G:GA	acceptor_gain	1.0000
12:6728222:GC:G	acceptor_gain	1.0000
12:6728222:GCT:G	acceptor_gain	1.0000
12:6728222:GCTG:G	acceptor_gain	1.0000
12:6728222:GCTGA:G	acceptor_gain	1.0000
12:6728224:T:A	acceptor_gain	1.0000
12:6728309:AAG:A	donor_gain	1.0000
12:6728311:GGT:G	donor_loss	1.0000
12:6728312:G:GG	donor_gain	1.0000
12:6728312:GTGA:G	donor_loss	1.0000
12:6729415:GACC:G	donor_gain	1.0000
12:6729445:G:GT	donor_gain	1.0000
12:6729446:A:T	donor_gain	1.0000
12:6729450:G:GG	donor_gain	1.0000
12:6730390:T:TA	acceptor_gain	1.0000
12:6730398:GCAG:G	acceptor_loss	1.0000
12:6730400:A:AG	acceptor_gain	1.0000
12:6730400:AG:A	acceptor_gain	1.0000
12:6730400:AGGT:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000966919 (12:6726419 T>C), RS1001415163 (12:6730757 T>C,G), RS1001808319 (12:6727061 G>C), RS1002867490 (12:6724334 G>C,T), RS1002897111 (12:6724159 G>A,T), RS1003760376 (12:6732146 A>T), RS1004872195 (12:6727134 C>T), RS1004956438 (12:6732083 G>A), RS1005091910 (12:6726848 G>T), RS1005333527 (12:6732313 AGAGT>A), RS1005545140 (12:6729864 T>C), RS1005683056 (12:6722694 G>A,C), RS1005731157 (12:6722920 T>G), RS1005741338 (12:6729006 G>A), RS1005930358 (12:6722741 C>A,G,T)

Disease associations

OMIM: gene MIM:616009 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002403_216	Red blood cell count	2.000000e-09
GCST90020028_1900	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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
bisphenol A	increases expression, affects cotreatment, decreases expression	4
Valproic Acid	affects expression, increases expression	3
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Selenium	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2UX	Abcam HEK293T COPS7A KO	Transformed cell line	Female
CVCL_SJ54	HAP1 COPS7A (-) 1	Cancer cell line	Male
CVCL_SJ55	HAP1 COPS7A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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