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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PSMC4
proteasome 26S subunit, ATPase 4
Chromosome 19 · 19q13.2
NCBI Gene: 5704Ensembl: ENSG00000013275.9HGNC: HGNC:9551UniProt: A8K2M0
326PubMed Papers
20Diseases
5Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnucleusnucleoplasmcytosolmultiple myelomaneoplasmMantle cell lymphomaHIV infection
✦AI Summary

PSMC4 (proteasome 26S subunit, ATPase 4) is a critical component of the 26S proteasome complex that functions as an AAA+ ATPase to unfold and translocate ubiquitinated proteins for degradation. As part of the heterohexameric AAA ring, PSMC4 plays essential roles in protein homeostasis by facilitating ATP-dependent proteolysis of misfolded, damaged, or regulatory proteins 1. The protein exhibits significant oncogenic potential across multiple cancer types, where overexpression correlates with poor prognosis and enhanced tumor progression 231. In prostate carcinoma, PSMC4 promotes progression through the CBX3-EGFR-PI3K-AKT-mTOR signaling pathway 2, while in low-grade gliomas, it regulates pathways including Notch, Toll-like receptor, and VEGF signaling 3. PSMC4 also functions in cellular processes beyond proteolysis, including cell extension formation in fibroblasts through Smad3 and ROCK signaling pathways 4. Additionally, PSMC4 serves as a component of immune-related prognostic signatures in osteosarcoma 5 and shows altered expression in dilated cardiomyopathy 6. The protein's expression can be downregulated by neurotoxic pesticides, potentially contributing to Parkinson's disease pathogenesis 7.

Sources cited
1
PSMC4 is an AAA+ ATPase component of 26S proteasome with oncogenic potential across multiple cancers
PMID: 39985882
2
PSMC4 promotes prostate carcinoma progression through CBX3-EGFR-PI3K-AKT-mTOR pathway
PMID: 37436074
3
PSMC4 overexpression in low-grade gliomas correlates with poor prognosis and regulates multiple signaling pathways
PMID: 41634888
4
PSMC4 is required for cell extension formation in fibroblasts via Smad3 and ROCK signaling
PMID: 29476834
5
PSMC4 is part of immune-related prognostic signatures in osteosarcoma
PMID: 37452172
6
PSMC4 expression is altered in dilated cardiomyopathy
PMID: 40074718
7
PSMC4 expression is downregulated by neurotoxic pesticides in neuroblastoma cells
PMID: 26498265
Disease Associationsⓘ20
multiple myelomaOpen Targets
0.60Moderate
neoplasmOpen Targets
0.51Moderate
Mantle cell lymphomaOpen Targets
0.50Moderate
HIV infectionOpen Targets
0.48Moderate
amyloidosisOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.27Weak
lymphomaOpen Targets
0.12Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
Waldenstrom macroglobulinemiaOpen Targets
0.11Weak
non-Hodgkins lymphomaOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.10Suggestive
leukemiaOpen Targets
0.10Suggestive
AL amyloidosisOpen Targets
0.10Suggestive
chronic graft versus host diseaseOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.08Suggestive
small cell lung carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
prostate cancerOpen Targets
0.08Suggestive
neuroendocrine carcinomaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets5
BORTEZOMIB D-MANNITOLApproved
26S proteasome inhibitor
Mantle cell lymphoma
CARFILZOMIBApproved
26S proteasome inhibitor
multiple myeloma
IXAZOMIBApproved
26S proteasome inhibitor
multiple myeloma
IXAZOMIB CITRATEApproved
26S proteasome inhibitor
multiple myeloma
OPROZOMIBPhase II
26S proteasome inhibitor
Hodgkins lymphoma
Related Genes
PSMD8Protein interaction100%PSMA1Protein interaction100%PSMA2Protein interaction100%PSMA3Protein interaction100%PSMA4Protein interaction100%PSMA5Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
100%
Brain
93%
Lung
75%
Bone Marrow
63%
Ovary
59%
Gene Interaction Network
Click a node to explore
PSMC4PSMD8PSMA1PSMA2PSMA3PSMA4PSMA5
PROTEIN STRUCTURE
Preparing viewer…
PDB2DVW · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.26 [0.17–0.41]
RankingsWhere PSMC4 stands among ~20K protein-coding genes
  • #1,006of 20,598
    Most Researched326 · top 5%
  • #372of 1,025
    FDA-Approved Drug Targets4
  • #2,067of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedPSMC4
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Discovering new hub genes of dilated cardiomyopathy.
PMID: 40074718
ESC Heart Fail · 2025
1.00
2
PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.
PMID: 37436074
J Cell Mol Med · 2023
0.90
3
Identification of suitable reference genes for real-time PCR analysis of statin-treated human umbilical vein endothelial cells.
PMID: 23251572
PLoS One · 2012
0.80
4
Genetic Cross-Talk between Oral Squamous Cell Carcinoma and Type 2 Diabetes: The Potential Role of Immunity.
PMID: 35634436
Dis Markers · 2022
0.72
5
PSMC4 promotes low-grade glioma progression and predicts poor prognosis.
PMID: 41634888
Eur J Med Res · 2026
0.70