COPS4

Summary

COPS4 (COP9 signalosome subunit 4, HGNC:16702) is a protein-coding gene on chromosome 4q21.22, encoding COP9 signalosome complex subunit 4 (Q9BT78). 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 96.7% of cancer cell lines).

This gene encodes one of eight subunits composing 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. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51138 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 43 total — 3 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 96.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_016129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16702
Approved symbol	COPS4
Name	COP9 signalosome subunit 4
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	CSN4, SGN4
Ensembl gene	ENSG00000138663
Ensembl biotype	protein_coding
OMIM	616008
Entrez	51138

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000264389, ENST00000503682, ENST00000504274, ENST00000506443, ENST00000507376, ENST00000509093, ENST00000509317, ENST00000510801, ENST00000511653, ENST00000511708, ENST00000511891, ENST00000873600, ENST00000873601, ENST00000873602, ENST00000873603, ENST00000928044, ENST00000942933, ENST00000942934

RefSeq mRNA: 3 — MANE Select: NM_016129 NM_001258006, NM_001330727, NM_016129

CCDS: CCDS3600, CCDS58909, CCDS82935

Canonical transcript exons

ENST00000264389 — 10 exons

Exon	Start	End
ENSE00000728547	83057258	83057408
ENSE00000728588	83063076	83063246
ENSE00000969786	83068438	83068522
ENSE00001073258	83056926	83057079
ENSE00001150240	83075297	83075818
ENSE00001150247	83035183	83035298
ENSE00003458479	83045626	83045705
ENSE00003468122	83049166	83049317
ENSE00003574881	83049881	83049984
ENSE00003635917	83066438	83066553

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 97.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4102 / max 775.5929, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48595	34.2257	1814
48594	2.1401	1289
48593	1.0444	759

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	97.48	gold quality
vastus lateralis	UBERON:0001379	97.30	gold quality
quadriceps femoris	UBERON:0001377	97.19	gold quality
deltoid	UBERON:0001476	97.01	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.00	gold quality
gluteal muscle	UBERON:0002000	96.86	gold quality
diaphragm	UBERON:0001103	96.76	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.59	gold quality
tibialis anterior	UBERON:0001385	96.41	gold quality
skeletal muscle tissue	UBERON:0001134	96.33	gold quality
heart right ventricle	UBERON:0002080	96.29	gold quality
muscle organ	UBERON:0001630	96.26	gold quality
skeletal muscle organ	UBERON:0014892	96.26	gold quality
secondary oocyte	CL:0000655	96.18	gold quality
muscle of leg	UBERON:0001383	96.03	gold quality
islet of Langerhans	UBERON:0000006	95.97	gold quality
gastrocnemius	UBERON:0001388	95.96	gold quality
substantia nigra pars compacta	UBERON:0001965	95.96	gold quality
triceps brachii	UBERON:0001509	95.91	gold quality
oocyte	CL:0000023	95.86	gold quality
muscle tissue	UBERON:0002385	95.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.50	gold quality
tibia	UBERON:0000979	95.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.21	gold quality
calcaneal tendon	UBERON:0003701	95.15	gold quality
oral cavity	UBERON:0000167	94.97	gold quality
prefrontal cortex	UBERON:0000451	94.80	gold quality
myocardium	UBERON:0002349	94.66	gold quality
pons	UBERON:0000988	94.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	1318.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting COPS4, 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-4682	100.00	68.89	1258
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-5579-3P	97.00	68.81	1111
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-5192	96.89	63.35	879

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Level in fetal Down syndrome brain found to be comparable to that of controls. (PMID:11824616)
• Identified is a novel-binding partner of torsin A, the subunit 4 (CSN4) of CSN signalosome. (PMID:21102408)
• CSN4 silencing decreases CSN5 protein levels and suggest that the CSN4 effects on sGCA1 and p53 proteins are mediated by CSN5. (PMID:24725084)
• CSN4 modulates the proliferation and apoptosis of breast cancer cells by regulating the expression of CDK6 and Caspase3 genes and thereby tumorigenesis (PMID:30992253)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cops4	ENSDARG00000043732
mus_musculus	Cops4	ENSMUSG00000035297
rattus_norvegicus	Cops4	ENSRNOG00000023650
drosophila_melanogaster	CSN4	FBGN0027054
caenorhabditis_elegans		WBGENE00000816

Paralogs (1): PSMD12 (ENSG00000197170)

Protein

Protein identifiers

COP9 signalosome complex subunit 4 — Q9BT78 (reviewed: Q9BT78)

Alternative names: JAB1-containing signalosome subunit 4

All UniProt accessions (6): Q9BT78, A0A0S2Z5H7, D6RAX7, D6RD63, D6REK7, D6RFN0

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. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, 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, COPS3, COPS5, COPS6, COPS7 (COPS7A or COPS7B) and COPS8. Interacts with TOR1A; the interaction is direct and associates TOR1A and SNAPIN with the CSN complex. Interacts with STON2; controls STON2 neddylation levels. Interacts with ERCC6.

Subcellular location. Cytoplasm. Nucleus. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle.

Similarity. Belongs to the CSN4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BT78-1	1	yes
Q9BT78-2	2

RefSeq proteins (3): NP_001244935, NP_001317656, NP_057213* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040134	PSMD12/CSN4	Family
IPR041406	CSN4_HTH	Domain
IPR054559	PSMD12-CSN4-like_N	Domain

Pfam: PF01399, PF18420, PF22241

UniProt features (38 total): helix 24, strand 4, turn 2, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
4D0P	X-RAY DIFFRACTION	1.6
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-Q9BT78-F1	94.79	0.91

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 (2): 2, 25

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: 172 (showing top): GOBP_PROTEIN_NEDDYLATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_DNA_REPAIR, ACEVEDO_LIVER_CANCER_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, chr4q21, GOCC_EXOCYTIC_VESICLE, GOCC_SECRETORY_VESICLE, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_SYNAPSE, GOCC_COP9_SIGNALOSOME

GO Biological Process (3): protein deneddylation (GO:0000338), protein neddylation (GO:0045116), regulation of protein neddylation (GO:2000434)

GO Molecular Function (2): deNEDDylase activity (GO:0019784), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), synaptic vesicle (GO:0008021), COP9 signalosome (GO:0008180), nuclear speck (GO:0016607), cell junction (GO:0030054), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), synapse (GO:0045202)

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	4
cytoplasm	2
protein modification by small protein removal	1
protein modification by small protein conjugation	1
protein neddylation	1
regulation of protein modification by small protein conjugation or removal	1
ubiquitin-like protein peptidase activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
exocytic vesicle	1
presynapse	1
nuclear protein-containing complex	1
nuclear ribonucleoprotein granule	1
intracellular vesicle	1
cellular_component	1
cell junction	1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COPS4	COPS8	Q99627	986
COPS4	COPS5	Q92905	979
COPS4	COPS7A	Q9UBW8	973
COPS4	COPS6	Q7L5N1	968
COPS4	COPS2	P61201	867
COPS4	COPS3	Q9UNS2	865
COPS4	COPS7B	Q9H9Q2	824
COPS4	GPS1	Q13098	814
COPS4	RBX1	P62877	750
COPS4	NEDD8	Q15843	735
COPS4	CUL4A	Q13619	668
COPS4	CUL1	Q13616	640
COPS4	CUL3	Q13618	570
COPS4	PSMD7	P51665	510
COPS4	DDB1	Q16531	500

IntAct

249 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
COPS6	COPS4	psi-mi:“MI:0915”(physical association)	0.920
COPS5	COPS2	psi-mi:“MI:0914”(association)	0.910
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
GPS1	COPS2	psi-mi:“MI:0915”(physical association)	0.860
COPS2	GPS1	psi-mi:“MI:0914”(association)	0.860
COPS8	COPS2	psi-mi:“MI:0914”(association)	0.850
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850

BioGRID (432): USHBP1 (Two-hybrid), COPS4 (Affinity Capture-RNA), COPS4 (Affinity Capture-RNA), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Affinity Capture-MS), COPS4 (Two-hybrid), COPS4 (Two-hybrid), USHBP1 (Two-hybrid), C19orf57 (Two-hybrid), MBIP (Two-hybrid)

ESM2 similar proteins: A0A8I3PI99, A0M8U1, A7Y521, B5DEN9, C5HGF3, O88544, O94973, P13666, P17427, P18484, P38024, Q00765, Q0VCK5, Q0X0A5, Q13098, Q1RLU8, Q28635, Q2PG42, Q3KNM2, Q3SZA0, Q3T0N3, Q3T126, Q3T178, Q3ZC24, Q4R5E6, Q5F418, Q5I0H4, Q5M7T4, Q5R648, Q5R9B0, Q5R9M4, Q5RE33, Q5ZJ41, Q5ZJD7, Q6DGW9, Q6GM44, Q6NRT5, Q7TQ48, Q8C407, Q8R1Z9

Diamond homologs: A7Y521, O88544, Q3SZA0, Q4R5E6, Q54B82, Q5R648, Q68FS2, Q6P0H6, Q7S0P8, Q8L5U0, Q9BT78, Q9C467, Q9N359, Q9V345, Q8VWK0, P68359

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
COPS4	“form complex”	“COP9 signalosome variant 2”	binding
COPS4	“form complex”	“COP9 signalosome variant 1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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	37.2×	4e-14
Formation of TC-NER Pre-Incision Complex	12	27.6×	2e-12
RHOBTB1 GTPase cycle	5	25.9×	1e-04
Neddylation	32	16.5×	3e-28
Cargo recognition for clathrin-mediated endocytosis	11	12.5×	1e-07
Activation of NF-kappaB in B cells	5	10.7×	6e-03
Antigen processing: Ubiquitination & Proteasome degradation	19	7.7×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
regulation of protein neddylation	9	72.6×	3e-13
protein neddylation	10	60.5×	1e-13
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	8	25.8×	1e-07
intrinsic apoptotic signaling pathway	6	18.6×	1e-04
protein monoubiquitination	5	14.8×	2e-03
cellular response to UV	5	12.7×	3e-03
G1/S transition of mitotic cell cycle	6	10.4×	2e-03
protein ubiquitination	26	9.3×	3e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
59456	GRCh38/hg38 4q21.21-21.23(chr4:81061483-83332595)x1	Pathogenic
59457	GRCh38/hg38 4q21.22-21.23(chr4:81733333-83448842)x1	Pathogenic
59458	GRCh38/hg38 4q21.22-21.23(chr4:81802008-83437114)x1	Pathogenic
442797	GRCh37/hg19 4q21.21-21.23(chr4:82359656-84155605)x1	Likely pathogenic

SpliceAI

1761 predictions. Top by Δscore:

Variant	Effect	Δscore
4:83035295:GCAA:G	donor_gain	1.0000
4:83035296:CAA:C	donor_gain	1.0000
4:83035297:AA:A	donor_gain	1.0000
4:83035297:AAG:A	donor_loss	1.0000
4:83035298:AG:A	donor_loss	1.0000
4:83035299:G:C	donor_loss	1.0000
4:83035299:G:GG	donor_gain	1.0000
4:83045621:TGTA:T	acceptor_loss	1.0000
4:83045623:TA:T	acceptor_loss	1.0000
4:83045624:A:AG	acceptor_gain	1.0000
4:83045624:A:T	acceptor_loss	1.0000
4:83045625:G:GG	acceptor_gain	1.0000
4:83045701:AGCAA:A	donor_gain	1.0000
4:83045702:GCAA:G	donor_gain	1.0000
4:83045702:GCAAG:G	donor_gain	1.0000
4:83045703:CAA:C	donor_gain	1.0000
4:83045704:AA:A	donor_gain	1.0000
4:83045704:AAG:A	donor_loss	1.0000
4:83045705:AGT:A	donor_loss	1.0000
4:83045706:G:GG	donor_gain	1.0000
4:83045706:G:T	donor_loss	1.0000
4:83045707:T:G	donor_loss	1.0000
4:83049159:A:AG	acceptor_gain	1.0000
4:83049160:A:AG	acceptor_gain	1.0000
4:83049161:A:AG	acceptor_gain	1.0000
4:83049162:C:G	acceptor_gain	1.0000
4:83049163:A:AG	acceptor_gain	1.0000
4:83049163:AAGT:A	acceptor_gain	1.0000
4:83049163:AAGTG:A	acceptor_gain	1.0000
4:83049164:A:AC	acceptor_loss	1.0000

AlphaMissense

2673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:83049183:A:C	S58R	1.000
4:83049185:T:A	S58R	1.000
4:83049185:T:G	S58R	1.000
4:83049187:T:A	L59H	1.000
4:83049190:T:A	V60E	1.000
4:83049196:C:G	S62W	1.000
4:83049199:G:C	R63P	1.000
4:83049208:T:C	L66P	1.000
4:83049295:G:T	R95I	1.000
4:83049296:A:C	R95S	1.000
4:83049296:A:T	R95S	1.000
4:83049306:T:C	F99L	1.000
4:83049307:T:C	F99S	1.000
4:83049308:T:A	F99L	1.000
4:83049308:T:G	F99L	1.000
4:83049309:G:A	E100K	1.000
4:83049310:A:T	E100V	1.000
4:83049311:G:C	E100D	1.000
4:83049311:G:T	E100D	1.000
4:83049903:T:C	L110P	1.000
4:83049905:G:C	A111P	1.000
4:83049941:G:C	A123P	1.000
4:83049945:C:A	A124D	1.000
4:83049971:G:A	E133K	1.000
4:83049977:G:A	G135R	1.000
4:83049977:G:C	G135R	1.000
4:83049978:G:A	G135E	1.000
4:83056945:A:G	K144E	1.000
4:83056947:A:C	K144N	1.000
4:83056947:A:T	K144N	1.000

dbSNP variants (sampled 300 via entrez): RS1000033981 (4:83057970 A>G), RS1000061061 (4:83063649 C>T), RS1000088340 (4:83063469 G>A), RS1000104430 (4:83071822 C>G,T), RS1000162087 (4:83074251 CTT>C,CTTT), RS1000296982 (4:83067526 T>A,C), RS1000299016 (4:83034065 T>G), RS1000340520 (4:83039102 T>G), RS1000382979 (4:83073888 T>A,C), RS1000520429 (4:83054211 A>G), RS1000525789 (4:83075490 C>T), RS1000556786 (4:83075847 C>T), RS1000640547 (4:83038079 C>G,T), RS1000670196 (4:83037767 C>T), RS1000692383 (4:83060660 T>C)

Disease associations

OMIM: gene MIM:616008 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1271	Metabolite levels	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010546	uridine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724761 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.47	IC50	340	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178661: Inhibition of COPS4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Ozone	increases oxidation, increases abundance, affects expression, affects cotreatment	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects 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
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Haloperidol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697391	Binding	Inhibition of COPS4 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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