COPS9

Summary

COPS9 (COP9 signalosome subunit 9, HGNC:21314) is a protein-coding gene on chromosome 2q37.3, encoding COP9 signalosome complex subunit 9 (Q8WXC6). Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.

Involved in cellular response to UV; negative regulation of protein neddylation; and positive regulation of cell population proliferation. Located in chromatin; cytoplasm; and nucleus.

Source: NCBI Gene 150678 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001163424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21314
Approved symbol	COPS9
Name	COP9 signalosome subunit 9
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	CSNAP
Ensembl gene	ENSG00000172428
Ensembl biotype	protein_coding
OMIM	619349
Entrez	150678

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000307266, ENST00000403160, ENST00000489698, ENST00000491765, ENST00000607357, ENST00000924049

RefSeq mRNA: 2 — MANE Select: NM_001163424 NM_001163424, NM_138336

CCDS: CCDS2532, CCDS63183

Canonical transcript exons

ENST00000607357 — 3 exons

Exon	Start	End
ENSE00001890368	240130828	240131088
ENSE00003574321	240133933	240134005
ENSE00003697081	240136222	240136305

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.3235 / max 509.7884, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34819	80.3235	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.37	gold quality
amygdala	UBERON:0001876	99.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.32	gold quality
putamen	UBERON:0001874	99.31	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.19	gold quality
caudate nucleus	UBERON:0001873	99.17	gold quality
substantia nigra	UBERON:0002038	99.16	gold quality
anterior cingulate cortex	UBERON:0009835	99.16	gold quality
prefrontal cortex	UBERON:0000451	99.15	gold quality
Ammon’s horn	UBERON:0001954	99.13	gold quality
spinal cord	UBERON:0002240	99.13	gold quality
nucleus accumbens	UBERON:0001882	99.12	gold quality
right frontal lobe	UBERON:0002810	99.10	gold quality
endothelial cell	CL:0000115	99.08	gold quality
midbrain	UBERON:0001891	99.07	gold quality
hypothalamus	UBERON:0001898	99.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.99	gold quality
left ventricle myocardium	UBERON:0006566	98.98	gold quality
apex of heart	UBERON:0002098	98.96	gold quality
frontal cortex	UBERON:0001870	98.95	gold quality
lateral globus pallidus	UBERON:0002476	98.95	gold quality
neocortex	UBERON:0001950	98.89	gold quality
temporal lobe	UBERON:0001871	98.88	gold quality
forebrain	UBERON:0001890	98.87	gold quality
cerebral cortex	UBERON:0000956	98.86	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.78	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.77	gold quality
adenohypophysis	UBERON:0002196	98.70	gold quality
brain	UBERON:0000955	98.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.98
E-HCAD-13	no	2.82
E-CURD-112	no	2.48

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Myeloma overexpressed 2 (Myeov2) regulates L11 subnuclear localization through Nedd8 modification. (PMID:23776465)
• CSNAP, the smallest CSN subunit, modulates proteostasis through cullin-RING ubiquitin ligases. (PMID:31367012)
• The disordered PCI-binding human proteins CSNAP and DSS1 have diverged in structure and function. (PMID:34272906)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops9	ENSDARG00000045296
drosophila_melanogaster	CG17059	FBGN0040754

Protein

Protein identifiers

COP9 signalosome complex subunit 9 — Q8WXC6 (reviewed: Q8WXC6)

Alternative names: CSN acidic protein, Myeloma-overexpressed gene 2 protein

All UniProt accessions (2): Q8WXC6, J3QT29

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. Plays a role in cell proliferation. Negatively regulates neddylation of proteins, including ribosoaml protein RPL11.

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 interacts directly with COPS3, COPS5 and COPS6. Isoform 2 associates with CSN complex. Isoform 2 interacts with COPS5, CUL1, CUL3 and RPL11. According to PubMed:26456823, does not associate with CSN complex.

Subcellular location. Nucleus. Cytoplasm. Nucleoplasm Nucleus. Nucleoplasm.

Domain organisation. The Phe/Asp-rich domain at the C-terminus is necessary for its incorporation into the CSN complex. Amino acids 60-89 in isoform 2 are necessary for interaction with COPS5, CUL1, CUL3.

Similarity. Belongs to the CSN9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WXC6-2	1, CSNAP	yes
Q8WXC6-1	2, MYEOV2-L

RefSeq proteins (2): NP_001156896, NP_612209 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029391	CSN9_metazoa	Family

Pfam: PF15004

UniProt features (7 total): splice variant 3, mutagenesis site 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9QO4	ELECTRON MICROSCOPY	2.95
9QO6	ELECTRON MICROSCOPY	3
9QO1	ELECTRON MICROSCOPY	3.23
9QO0	ELECTRON MICROSCOPY	3.26
9QO2	ELECTRON MICROSCOPY	3.8
9QO5	ELECTRON MICROSCOPY	4
9QO3	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXC6-F1	62.86	0.00

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): 26

Mutagenesis-validated functional residues (2):

Position	Phenotype
44	does not abolish interaction with csn complex. abolishes interaction with csn complex; when associated with a-51.
51	decreases interaction with csn complex. abolishes interaction with csn complex; when associated with a-44.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_PROTEIN_NEDDYLATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MARTINEZ_RB1_TARGETS_DN, GOBP_RESPONSE_TO_UV, GOBP_RESPONSE_TO_RADIATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_RADIATION, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_NUCLEUS

GO Biological Process (4): positive regulation of cell population proliferation (GO:0008284), cellular response to UV (GO:0034644), negative regulation of protein localization to nucleolus (GO:1904750), negative regulation of protein neddylation (GO:2000435)

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

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), COP9 signalosome (GO:0008180)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to UV	1
cellular response to light stimulus	1
negative regulation of protein localization to nucleus	1
protein localization to nucleolus	1
regulation of protein localization to nucleolus	1
protein neddylation	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of protein neddylation	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS9	COPS8	Q99627	700
COPS9	COPS6	Q7L5N1	522
COPS9	TCEAL9	Q9UHQ7	517
COPS9	CUL3	Q13618	487
COPS9	OTOS	Q8NHW6	438
COPS9	SNAP25	P13795	435
COPS9	COPS4	Q9BT78	431
COPS9	COPS7A	Q9UBW8	418
COPS9	GPR160	Q9UJ42	412
COPS9	MYEOV	Q96EZ4	397
COPS9	SAMD7	Q7Z3H4	396
COPS9	COPS5	Q92905	394
COPS9	SENP8	Q96LD8	370
COPS9	CCDC15	Q0P6D6	367
COPS9	ZNF227	Q86WZ6	367

IntAct

24 interactions, top by confidence:

A	B	Type	Score
COPS5	CUL4A	psi-mi:“MI:0914”(association)	0.840
COPS3	HBB	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
NEDD8	DDX3X	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
COPS6		psi-mi:“MI:0914”(association)	0.350
DDB1	POLRMT	psi-mi:“MI:0914”(association)	0.350
COPS9	KLHL18	psi-mi:“MI:0914”(association)	0.350
ZRANB3	COPS9	psi-mi:“MI:0914”(association)	0.350
COPS2	PXDNL	psi-mi:“MI:0914”(association)	0.350
COPS3	POTEF	psi-mi:“MI:0914”(association)	0.350
COPS8	UBB	psi-mi:“MI:0914”(association)	0.350
COPS2	RHOBTB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (80): MYEOV2 (Affinity Capture-MS), MYEOV2 (Affinity Capture-RNA), GPS1 (Affinity Capture-Western), COPS3 (Affinity Capture-Western), COPS5 (Affinity Capture-Western), COPS8 (Affinity Capture-Western), GPS1 (Co-fractionation), COPS3 (Co-fractionation), COPS8 (Co-fractionation), MYEOV2 (Affinity Capture-Western), MYEOV2 (Affinity Capture-Western), COPS3 (Reconstituted Complex), COPS5 (Reconstituted Complex), COPS6 (Reconstituted Complex), MYEOV2 (Affinity Capture-MS)

ESM2 similar proteins: A0L486, A1A0T8, A1L3P1, A4VVZ9, A4W2A7, A5VPI8, A6NMA1, A6U7A2, A6X296, A7HX41, A7IM18, A9MA26, B0CKX7, B2IIA1, B2SAC9, B6IN07, B7GUQ0, B8DTW7, C0HK64, C0RHZ3, F5HGI9, K4JY29, O13619, O94688, P08804, P16792, P85800, Q17684, Q2RT88, Q2W519, Q2YN12, Q32PD7, Q3U898, Q55GR4, Q57E91, Q5RDL6, Q6DDA3, Q6FM20, Q6G465, Q6NVV0

Diamond homologs: A1L3P1, Q32PD7, Q3U898, Q6DDA3, Q6P6E6, Q7JVR7, Q8WXC6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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	129.8×	6e-18
Formation of TC-NER Pre-Incision Complex	10	96.1×	1e-16
Cargo recognition for clathrin-mediated endocytosis	8	38.1×	9e-10
Neddylation	16	34.5×	2e-20
Antigen processing: Ubiquitination & Proteasome degradation	5	8.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	7	234.1×	6e-14
protein neddylation	8	200.6×	3e-15
intrinsic apoptotic signaling pathway	6	76.8×	7e-09
G1/S transition of mitotic cell cycle	6	43.0×	2e-07
protein ubiquitination	9	13.3×	5e-07
ubiquitin-dependent protein catabolic process	5	13.3×	8e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	7	13.0×	2e-05
DNA damage response	5	9.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
997054	GRCh37/hg19 2q37.3(chr2:239860877-241385960)	Pathogenic
625780	GRCh37/hg19 2q37.3(chr2:238795602-242918203)	Likely pathogenic

SpliceAI

714 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240136187:C:A	donor_gain	1.0000
2:240136203:C:CA	donor_gain	1.0000
2:240136226:T:TA	donor_gain	1.0000
2:240136239:AGGG:A	donor_gain	1.0000
2:240136239:AGGGC:A	donor_gain	1.0000
2:240133927:CCTTA:C	donor_loss	0.9900
2:240133928:CTTAC:C	donor_loss	0.9900
2:240133929:TTACC:T	donor_loss	0.9900
2:240133930:T:TG	donor_loss	0.9900
2:240133932:CCGT:C	donor_loss	0.9900
2:240134001:CCCGC:C	acceptor_gain	0.9900
2:240134002:CCGCC:C	acceptor_gain	0.9900
2:240134004:GCC:G	acceptor_loss	0.9900
2:240134007:T:A	acceptor_loss	0.9900
2:240136179:C:A	donor_gain	0.9900
2:240136186:C:CA	donor_gain	0.9900
2:240136191:CG:C	donor_gain	0.9900
2:240136204:C:A	donor_gain	0.9900
2:240136223:T:TA	donor_gain	0.9900
2:240133828:C:CT	donor_gain	0.9800
2:240134002:CCGC:C	acceptor_gain	0.9800
2:240134003:CGCC:C	acceptor_gain	0.9800
2:240134006:C:CC	acceptor_gain	0.9800
2:240136173:C:A	donor_gain	0.9800
2:240136178:T:TA	donor_gain	0.9800
2:240136250:C:CA	donor_gain	0.9800
2:240131089:C:CC	acceptor_gain	0.9700
2:240133931:A:AC	donor_gain	0.9700
2:240133932:C:CC	donor_gain	0.9700
2:240136166:T:TA	donor_gain	0.9700

AlphaMissense

389 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240136259:A:C	F9C	0.997
2:240136258:G:C	F9L	0.996
2:240136258:G:T	F9L	0.996
2:240136260:A:G	F9L	0.996
2:240136259:A:G	F9S	0.995
2:240133974:A:G	L32S	0.994
2:240133953:A:T	V39D	0.993
2:240136251:C:G	G12R	0.993
2:240136269:C:G	D6H	0.991
2:240133983:A:G	L29S	0.990
2:240136260:A:C	F9V	0.990
2:240136260:A:T	F9I	0.989
2:240133940:A:C	F43L	0.987
2:240133940:A:T	F43L	0.987
2:240133942:A:G	F43L	0.987
2:240136262:A:G	M8T	0.987
2:240133974:A:C	L32W	0.986
2:240136251:C:A	G12C	0.985
2:240136268:T:A	D6V	0.985
2:240133941:A:G	F43S	0.984
2:240136245:C:A	G14W	0.984
2:240133962:T:A	E36V	0.981
2:240133977:T:A	D31V	0.981
2:240136245:C:G	G14R	0.981
2:240136245:C:T	G14R	0.981
2:240136265:T:A	E7V	0.980
2:240136269:C:T	D6N	0.977
2:240136244:C:T	G14E	0.976
2:240136256:G:T	P10H	0.975
2:240133994:G:C	S25R	0.974

dbSNP variants (sampled 300 via entrez): RS1000063454 (2:240129307 C>T), RS1000504538 (2:240132586 G>A,C), RS1000667551 (2:240128236 G>C), RS1001238557 (2:240134708 T>G), RS1001302797 (2:240136410 C>A,T), RS1001663020 (2:240127109 G>A), RS1001779187 (2:240126898 C>T), RS1002308731 (2:240135380 T>C), RS1002468390 (2:240129483 G>C), RS1002519284 (2:240130515 C>G,T), RS1002611274 (2:240135546 G>C), RS1002781491 (2:240129334 T>C,G), RS1002959220 (2:240132512 G>A,C), RS1002962021 (2:240130367 G>A), RS1003203066 (2:240131249 C>G,T)

Disease associations

OMIM: gene MIM:619349 | disease phenotypes: MIM:600430, MIM:173800

GenCC curated gene-disease

Mondo (2): 2q37 microdeletion syndrome (MONDO:0010886), Poland syndrome (MONDO:0008262)

Orphanet (2): 2q37 microdeletion syndrome (Orphanet:1001), Poland syndrome (Orphanet:2911)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011045	Poland Syndrome	C05.116.099.370.894.819.756; C05.660.585.800.756; C05.660.906.819.756; C16.131.621.585.800.756; C16.131.621.906.819.756
C538317	Chromosome 2q37 deletion syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
Valproic Acid	increases expression, affects expression	2
aristolochic acid I	increases expression	1
arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	increases expression, increases abundance	1
Dietary Carbohydrates	increases expression	1
Doxorubicin	increases expression	1
Ozone	affects methylation, increases abundance	1
Smoke	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ56	HAP1 MYEOV2 (-) 1	Cancer cell line	Male
CVCL_SZ57	HAP1 MYEOV2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
NCT06146231	Not specified	RECRUITING	Motiva Flora® Aesthetic Breast Recon® Clinical Study