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GeneE
9 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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COPS4
COP9 signalosome subunit 4
Chromosome 4 · 4q21.22
NCBI Gene: 51138Ensembl: ENSG00000138663.10HGNC: HGNC:16702UniProt: A0A0S2Z5H7
168PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytoplasmprotein deneddylationnuclear speckneurodegenerative diseasecervical carcinomaatrial fibrillationmetabolic syndrome
✦AI Summary

COPS4 encodes a core subunit of the COP9 signalosome (CSN), a multifunctional protein complex essential for cellular regulation. As a structural component of CSN, COPS4 maintains complex integrity and participates in deneddylation of cullin-containing E3 ubiquitin ligases, thereby modulating the ubiquitin-proteasome degradation pathway 1. The complex also associates with kinases like CK2 and PKD to phosphorylate regulatory proteins including p53, c-Jun, and IκBα, controlling their stability and function 2. COPS4 expression is significantly elevated in multiple cancer types including cholangiocarcinoma, hepatocellular carcinoma, esophageal squamous cell carcinoma, and head/neck cancers, where elevated levels correlate with advanced pathological stage, nodal involvement, and metastatic status 3. In breast cancer, COPS4 is a frequently recognized autoantigen, with elevated IgG responses associated with shorter recurrence-free survival and lower CD8+ T cell infiltration 4. Mechanistically, COPS4 knockdown in breast cancer cells reduces proliferation and induces apoptosis via modulation of CDK6 and Caspase3 expression 5. In prostate cancer, COPS4 prevents proteasomal degradation of soluble guanylyl cyclase α1 while promoting p53 degradation, supporting tumor survival 2. COPS4 dysregulation through gene amplification, mutations, and promoter hypomethylation drives overexpression in tumors 3, positioning it as a prognostic biomarker and potential therapeutic target across multiple malignancies.

Sources cited
1
COPS4 is upregulated in multiple cancer types (CHOL, HNSC, ESCA, LIHC) with associations to clinical stage, grade, nodal involvement, metastatic status, and immune cell infiltration; identified as prognostic biomarker and therapeutic target
PMID: 40424765
2
COPS4 is frequently recognized as an autoantigen in breast cancer; elevated IgG responses correlate with shorter recurrence-free survival and lower CD8+ T cell infiltration
PMID: 30515157
3
COPS4 identified as part of secondary fusion transcripts in sarcomas (COPS4-TBC1D9)
PMID: 36232302
4
COPS4 is one of seven COP9 genes with highly coordinated expression in normal tissues; COP9 complex possesses deneddylase activity to modulate oncogenic protein concentrations
PMID: 27903243
5
COPS4 is identified within the critical region for 4q21.22 microdeletion syndrome, with low frequency of truncating mutations suggesting haploinsufficiency risk
PMID: 28371330
6
CSN4/COPS4 interacts with tescalcin in calcium-dependent manner and regulates deneddylation of cullin-1 and stability of p27 and p53 during cell differentiation
PMID: 24659803
7
COPS4 knockdown in MDA-MB-231 breast cancer cells decreases proliferation, induces apoptosis, and regulates CDK6 and Caspase3 expression
PMID: 30992253
8
COPS4 protects soluble guanylyl cyclase α1 from proteasomal degradation while promoting p53 degradation via CSN5-CK2 complex in prostate cancer; COPS4 overexpression correlates with sGCα1 and inverse correlation with p53 in tumors
PMID: 24725084
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
cervical carcinomaOpen Targets
0.27Weak
atrial fibrillationOpen Targets
0.11Weak
metabolic syndromeOpen Targets
0.07Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.04Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin E diseaseOpen Targets
0.04Suggestive
delta-beta-thalassemiaOpen Targets
0.04Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.04Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
hemoglobin H diseaseOpen Targets
0.04Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.03Suggestive
Blackfan-Diamond anemiaOpen Targets
0.03Suggestive
hypertensionOpen Targets
0.03Suggestive
beta-thalassemia-X-linked thrombocytopenia syndromeOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CRBNProtein interaction100%CUL3Protein interaction100%ELOCProtein interaction100%CUL1Protein interaction100%ELOBProtein interaction100%PSMD6Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
66%
Bone Marrow
54%
Ovary
35%
Lung
31%
Liver
25%
Gene Interaction Network
Click a node to explore
COPS4CRBNCUL3ELOCCUL1ELOBPSMD6
PROTEIN STRUCTURE
Preparing viewer…
PDB4D0P · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.07–0.30]
RankingsWhere COPS4 stands among ~20K protein-coding genes
  • #2,645of 20,598
    Most Researched168 · top quartile
  • #1,182of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedCOPS4
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
COPS4 is a novel prognostic biomarker and potential therapeutic target involved in regulation of immune microenvironment in numerous cancers.
PMID: 40424765
Comput Biol Med · 2025
1.00
2
Antigen Specificity and Clinical Significance of IgG and IgA Autoantibodies Produced
PMID: 30515157
Front Immunol · 2018
0.89
3
mRNA Capture Sequencing and RT-qPCR for the Detection of Pathognomonic, Novel, and Secondary Fusion Transcripts in FFPE Tissue: A Sarcoma Showcase.
PMID: 36232302
Int J Mol Sci · 2022
0.78
4
Analysis of RNA expression of normal and cancer tissues reveals high correlation of COP9 gene expression with respiratory chain complex components.
PMID: 27903243
BMC Genomics · 2016
0.67
5
A de novo deletion in a boy with cerebral palsy suggests a refined critical region for the 4q21.22 microdeletion syndrome.
PMID: 28371330
Am J Med Genet A · 2017
0.56