COPS2

Summary

COPS2 (COP9 signalosome subunit 2, HGNC:30747) is a protein-coding gene on chromosome 15q21.1, encoding COP9 signalosome complex subunit 2 (P61201). Essential 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 97.1% of cancer cell lines).

Predicted to enable transcription corepressor activity. Involved in protein deneddylation and protein phosphorylation. Located in cytoplasm and nucleus. Part of COP9 signalosome.

Source: NCBI Gene 9318 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_004236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30747
Approved symbol	COPS2
Name	COP9 signalosome subunit 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	TRIP15, ALIEN, CSN2
Ensembl gene	ENSG00000166200
Ensembl biotype	protein_coding
OMIM	604508
Entrez	9318

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000299259, ENST00000388901, ENST00000542928, ENST00000558545, ENST00000558843, ENST00000559016, ENST00000560240, ENST00000561248, ENST00000882488, ENST00000882489, ENST00000882490, ENST00000882491, ENST00000882492, ENST00000940241

RefSeq mRNA: 2 — MANE Select: NM_004236 NM_001143887, NM_004236

CCDS: CCDS32235, CCDS45257

Canonical transcript exons

ENST00000388901 — 13 exons

Exon	Start	End
ENSE00001100871	49129477	49129559
ENSE00001100874	49128702	49128760
ENSE00001100890	49133759	49133811
ENSE00001100894	49133930	49134108
ENSE00001100896	49130719	49130816
ENSE00001100902	49139528	49139653
ENSE00001181399	49122727	49128094
ENSE00001504345	49134340	49134514
ENSE00001504346	49137348	49137437
ENSE00002537006	49155525	49155599
ENSE00003529743	49137150	49137227
ENSE00003561024	49144227	49144304
ENSE00003621712	49144965	49145078

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.8120 / max 1440.3867, expressed in 1801 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149815	51.0624	1801
149816	0.4131	172
149814	0.3366	123

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.01	gold quality
diaphragm	UBERON:0001103	98.72	gold quality
calcaneal tendon	UBERON:0003701	98.43	gold quality
parietal pleura	UBERON:0002400	98.34	gold quality
gingival epithelium	UBERON:0001949	98.20	gold quality
cauda epididymis	UBERON:0004360	98.13	gold quality
gluteal muscle	UBERON:0002000	98.07	gold quality
esophagus squamous epithelium	UBERON:0006920	98.03	gold quality
amniotic fluid	UBERON:0000173	98.02	gold quality
corpus epididymis	UBERON:0004359	97.95	gold quality
gingiva	UBERON:0001828	97.93	gold quality
germinal epithelium of ovary	UBERON:0001304	97.84	gold quality
caput epididymis	UBERON:0004358	97.82	gold quality
deltoid	UBERON:0001476	97.81	gold quality
pleura	UBERON:0000977	97.77	gold quality
squamous epithelium	UBERON:0006914	97.77	gold quality
tendon	UBERON:0000043	97.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.73	gold quality
biceps brachii	UBERON:0001507	97.59	gold quality
endometrium	UBERON:0001295	97.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.53	gold quality
visceral pleura	UBERON:0002401	97.50	gold quality
decidua	UBERON:0002450	97.50	gold quality
tibia	UBERON:0000979	97.46	gold quality
tibialis anterior	UBERON:0001385	97.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.40	gold quality
triceps brachii	UBERON:0001509	97.35	gold quality
islet of Langerhans	UBERON:0000006	97.34	gold quality
myocardium	UBERON:0002349	97.33	gold quality
mammalian vulva	UBERON:0000997	97.32	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, ZNF335

miRNA regulators (miRDB)

145 targeting COPS2, 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-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
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-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• demonstrate Alien-MLK2 interaction and also show that MLK2 is able to phosphorylate Alien; Alien, DAX-1 and thyroid hormone receptor mediated transcriptional silencing is strongly enhanced in the presence of active MLK2 (PMID:15062575)
• Alien and Sin3A reside together in vivo with the vitamin D3 receptor on the human 24-hydroxylase (CYP24) promoter containing vitamin D3 response elements by chromatin immunoprecipitation (PMID:15173382)
• Data show that Alien binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. (PMID:17339334)
• Protein interactions of Alien involving nucleophosmin, ERCC3, TRIP11, as well as CRSP3. (PMID:17438371)
• Alien inhibits E2F1 gene expression and cell proliferation. (PMID:17570542)
• the interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network (PMID:17929852)
• CSN2 gene was identified in the genome-wide loss-of-function genetic screen as putative tumor suppressor located at 15q21.2. (PMID:17968325)
• Alien seems to modulate nucleosome assembly activity. This suggests that Alien is acting on chromatin not only through recruitment of histone-modifying activities, but also through enhancing nucleosome assembly. (PMID:18174916)
• CSN2 knockdown cells underwent non-apoptotic cell death. (PMID:19400951)
• A subunit of the COP9 signalosome interacted physically with the anaphase-promoting complex and showed a genetic instability of cells. (PMID:19535905)
• p300 binds to Alien alpha by pull down (View interaction) Alien alpha physically interacts with CBP by two hybrid (PMID:23441852)
• Data indicate that DET1- and DDB1-associated protein 1 (DDA1)-mediated tumor progression is associated with the activation of the NF-kappa B (NFkappaB)/COP9 signalosome 2(CSN2)/glycogen synthase kinase3beta (GSK3beta) pathway. (PMID:26942699)
• AIBP promotes apoA-1 binding to ABCA1 on the cell membrane of macrophages and prevents ABCA1 protein from CSN2-mediated degradation so as to prevent foam cell formation (PMID:27017521)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops2	ENSDARG00000004785
mus_musculus	Cops2	ENSMUSG00000027206
rattus_norvegicus	Cops2	ENSRNOG00000008744
drosophila_melanogaster	alien	FBGN0013746
caenorhabditis_elegans	csn-2	WBGENE00000814

Paralogs (1): PSMD11 (ENSG00000108671)

Protein

Protein identifiers

COP9 signalosome complex subunit 2 — P61201 (reviewed: P61201)

Alternative names: Alien homolog, JAB1-containing signalosome subunit 2, Thyroid receptor-interacting protein 15

All UniProt accessions (5): B4DIH5, P61201, H0YKU5, H0YM03, H0YMC2

UniProt curated annotations — full annotation on UniProt →

Function. Essential 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. Involved in early stage of neuronal differentiation via its interaction with NIF3L1.

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, COPS5, COPS6 and COPS7 (COPS7A or COPS7B). Specifically interacts with the ligand binding domain of the thyroid receptor (TR). Does not require the presence of thyroid hormone for its interaction. Interacts with CUL1 and CUL2. Interacts with IRF8/ICSBP1 and with nuclear receptors NR2F1 and NR0B1. Interacts with NIF3L1.

Subcellular location. Cytoplasm. Nucleus.

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

Similarity. Belongs to the CSN2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P61201-1	1	yes
P61201-2	2

RefSeq proteins (2): NP_001137359, NP_004227* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050871	26S_Proteasome/COP9_Components	Family
IPR058796	COPS2_C	Domain

Pfam: PF01399, PF25983

UniProt features (16 total): helix 7, sequence conflict 5, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
6A73	X-RAY DIFFRACTION	2.45
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-P61201-F1	85.22	0.50

Function

Pathways and Gene Ontology

Reactome pathways

5 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
R-HSA-9013422	RHOBTB1 GTPase cycle

MSigDB gene sets: 344 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_GROWTH, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_PROTEIN_NEDDYLATION, GOBP_NEUROGENESIS, REACTOME_MEMBRANE_TRAFFICKING, MODULE_16, PID_REG_GR_PATHWAY, MODULE_308, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_MONOATOMIC_CATION_TRANSPORT, chr4q13, GOBP_INNER_CELL_MASS_CELL_PROLIFERATION

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), protein deneddylation (GO:0000338), inner cell mass cell proliferation (GO:0001833), trophectodermal cell proliferation (GO:0001834), transcription by RNA polymerase II (GO:0006366), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), neuron differentiation (GO:0030182), skeletal muscle cell differentiation (GO:0035914), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (2): transcription corepressor activity (GO:0003714), 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-5 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
RHOBTB GTPase Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
blastocyst growth	2
cell population proliferation	2
DNA-templated transcription	2
cell differentiation	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
protein modification by small protein removal	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
generation of neurons	1
skeletal muscle tissue development	1
protein modification by small protein conjugation	1
protein neddylation	1
regulation of protein modification by small protein conjugation or removal	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	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

1932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS2	COPS3	Q9UNS2	981
COPS2	GPS1	Q13098	948
COPS2	COPS5	Q92905	926
COPS2	COPS4	Q9BT78	867
COPS2	COPS6	Q7L5N1	829
COPS2	COPS7A	Q9UBW8	815
COPS2	COPS8	Q99627	811
COPS2	COPS7B	Q9H9Q2	803
COPS2	RBX1	P62877	783
COPS2	CUL4A	Q13619	777
COPS2	DDB2	Q92466	671
COPS2	NIF3L1	Q9GZT8	656
COPS2	THRB	P10828	655
COPS2	TXNRD2	Q9NNW7	653
COPS2	DDB1	Q16531	636

IntAct

228 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
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 (572): CUL4A (Reconstituted Complex), COPS2 (Affinity Capture-Western), IP6K1 (Reconstituted Complex), COPS2 (Affinity Capture-Western), COPS2 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), COPS2 (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)

ESM2 similar proteins: A0A1L8F5J9, A0JN27, F1LTR1, F1NBL0, O15294, P35438, P35439, P56558, P61201, P61202, P61203, P61599, P61600, P63138, P79101, P81436, Q03555, Q05586, Q13888, Q15303, Q27HV0, Q2PFM2, Q2TBV5, Q4L208, Q58ED9, Q5R1P0, Q5SP67, Q5ZJ75, Q61527, Q62956, Q6IQT4, Q6IR75, Q6P1K8, Q6P632, Q7ZXR3, Q8BUV3, Q8C6G8, Q8CGY8, Q8R4D1, Q91854

Diamond homologs: O01422, P61201, P61202, P61203, Q54HL6, Q5B3U7, Q6IQT4, Q6IR75, Q7SI58, Q8W207, Q94899, Q9HFR0, F1QGH9, Q9GS00

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
COPS2	“form complex”	“COP9 signalosome variant 2”	binding
COPS2	“form complex”	“COP9 signalosome variant 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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	13	35.0×	5e-15
Formation of TC-NER Pre-Incision Complex	13	25.9×	2e-13
Neddylation	37	16.5×	5e-33
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	5	12.5×	4e-03
Dual Incision in GG-NER	5	12.2×	4e-03
Formation of Incision Complex in GG-NER	5	12.0×	4e-03
Cargo recognition for clathrin-mediated endocytosis	12	11.9×	4e-08
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	10.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	9	65.3×	9e-13
protein neddylation	10	54.4×	4e-13
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	9	26.1×	7e-09
intrinsic apoptotic signaling pathway	7	19.5×	7e-06
cellular response to UV	5	11.5×	5e-03
G1/S transition of mitotic cell cycle	7	10.9×	3e-04
protein ubiquitination	33	10.6×	7e-22
proteasome-mediated ubiquitin-dependent protein catabolic process	22	8.9×	1e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1714 predictions. Top by Δscore:

Variant	Effect	Δscore
15:49128090:TAGTG:T	acceptor_gain	1.0000
15:49128091:AGTG:A	acceptor_gain	1.0000
15:49128092:GTG:G	acceptor_gain	1.0000
15:49128092:GTGC:G	acceptor_loss	1.0000
15:49128093:TG:T	acceptor_gain	1.0000
15:49128095:C:CA	acceptor_loss	1.0000
15:49128095:C:CC	acceptor_gain	1.0000
15:49128698:TTAC:T	donor_loss	1.0000
15:49128699:TAC:T	donor_loss	1.0000
15:49128700:A:AC	donor_gain	1.0000
15:49128700:ACTTA:A	donor_loss	1.0000
15:49128701:C:CT	donor_gain	1.0000
15:49128701:CT:C	donor_gain	1.0000
15:49128701:CTT:C	donor_gain	1.0000
15:49128701:CTTA:C	donor_gain	1.0000
15:49128701:CTTAT:C	donor_gain	1.0000
15:49128704:AT:A	donor_gain	1.0000
15:49128705:T:C	donor_gain	1.0000
15:49128758:CTC:C	acceptor_gain	1.0000
15:49128760:CCTAA:C	acceptor_loss	1.0000
15:49128761:C:A	acceptor_loss	1.0000
15:49128761:C:CC	acceptor_gain	1.0000
15:49130714:CATA:C	donor_loss	1.0000
15:49130715:ATACC:A	donor_loss	1.0000
15:49130716:TA:T	donor_loss	1.0000
15:49130717:A:AC	donor_gain	1.0000
15:49130717:AC:A	donor_gain	1.0000
15:49130718:C:CC	donor_gain	1.0000
15:49130718:CC:C	donor_gain	1.0000
15:49130718:CCTT:C	donor_gain	1.0000

AlphaMissense

2971 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:49128723:A:G	L389P	1.000
15:49129529:A:G	L359P	1.000
15:49130775:A:G	L330P	1.000
15:49133810:G:T	A299D	1.000
15:49133811:C:G	A299P	1.000
15:49133932:C:T	E298K	1.000
15:49133938:A:G	S296P	1.000
15:49133967:A:G	L286P	1.000
15:49133994:A:G	L277S	1.000
15:49133996:G:C	C276W	1.000
15:49133997:C:T	C276Y	1.000
15:49133998:A:G	C276R	1.000
15:49134018:C:T	G269E	1.000
15:49134025:C:T	E267K	1.000
15:49134028:C:G	D266H	1.000
15:49134035:C:A	K263N	1.000
15:49134035:C:G	K263N	1.000
15:49134038:G:C	F262L	1.000
15:49134038:G:T	F262L	1.000
15:49134040:A:G	F262L	1.000
15:49134043:C:G	A261P	1.000
15:49134099:C:A	G242V	1.000
15:49134099:C:T	G242D	1.000
15:49134100:C:G	G242R	1.000
15:49134102:C:T	G241D	1.000
15:49134103:C:G	G241R	1.000
15:49134341:T:A	R238S	1.000
15:49134341:T:G	R238S	1.000
15:49134342:C:A	R238I	1.000
15:49134342:C:G	R238T	1.000

dbSNP variants (sampled 300 via entrez): RS1000081953 (15:49139691 T>C,G), RS1000153063 (15:49140534 T>C), RS1000249973 (15:49140837 G>A,C), RS1000388594 (15:49127240 C>G), RS1000471338 (15:49133224 G>A,C), RS1000579215 (15:49157464 C>G,T), RS1000640215 (15:49122459 C>A,G), RS1000781503 (15:49139317 T>C), RS1000822599 (15:49129137 C>A,G), RS1000875123 (15:49153341 A>G), RS1000883746 (15:49127508 T>C), RS1001116179 (15:49140690 C>T), RS1001127270 (15:49128816 A>G), RS1001329466 (15:49140161 T>A), RS1001378705 (15:49153171 G>A)

Disease associations

OMIM: gene MIM:604508 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004744_31	Lung adenocarcinoma	2.000000e-16
GCST004748_33	Lung cancer	1.000000e-09
GCST007430_56	Peak expiratory flow	4.000000e-13
GCST007431_23	Lung function (FEV1/FVC)	3.000000e-23

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067242 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
GSK-J4	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
kojic acid	decreases expression	1
tetrahydropalmatine	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
indirubin	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Coumestrol	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	increases abundance, affects expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Taurine	increases expression	1
Valproic Acid	decreases methylation	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
CHEMBL5651162	Binding	Binding affinity to human COPS2 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.