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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PSMD9
proteasome 26S subunit, non-ATPase 9
Chromosome 12 · 12q24.31
NCBI Gene: 5715Ensembl: ENSG00000110801.15HGNC: HGNC:9567UniProt: O00233
161PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
proteasome regulatory particle, base subcomplexproteasome regulatory particle assemblyprotein bindingcytosolneoplasmbreast cancerhepatocellular carcinomacancer
✦AI Summary

PSMD9 (proteasome 26S subunit, non-ATPase 9) is a multifunctional chaperone protein with primary roles in proteasome assembly and beyond. As a canonical function, PSMD9 acts as an assembly chaperone during 26S proteasome base subcomplex formation, participating in the intermediate PSMD9:PSMC6:PSMC3 modulator trimer complex before being released during final assembly 1. Recently identified functions extend far beyond proteasome biology. PSMD9 was discovered as a lipid regulatory protein involved in controlling mammalian lipid metabolism and hepatosteatosis pathogenesis 2. In cancer contexts, PSMD9 expression is elevated and prognostically significant across multiple malignancies. In glioblastoma, PSMD9 knockdown inhibits cell proliferation, invasion, migration, and induces G2/M arrest, with high expression conferring resistance to panobinostat 3. In hepatocellular carcinoma, PSMD9 promotes progression by interacting with E3 ubiquitin ligase c-Cbl to suppress EGFR ubiquitination and activate ERK1/2/Akt signaling, with PSMD9 knockdown sensitizing cells to erlotinib 4. In metastatic prostate cancer, PSMD9 participates in an m6A-modified enhancer RNA regulatory complex affecting radiotherapy resistance 5. PSMD9 also shows associations with immune responses and proteostasis regulation, with elevated serum levels in long-term responders to immunotherapy 6 and identified as a risk factor for osteosarcopenia 7. The protein's multifunctionality relies primarily on protein-protein interactions rather than enzymatic activity 8.

Sources cited
1
PSMD9 identified as a lipid regulatory protein involved in lipid homeostasis and hepatosteatosis pathogenesis through systems genetic analysis
PMID: 30814737
2
PSMD9 knockdown inhibits GBM cell proliferation, invasion, migration, and induces G2/M arrest; high PSMD9 confers panobinostat resistance
PMID: 37485655
3
PSMD9 promotes HCC progression by interacting with c-Cbl to suppress EGFR ubiquitination and activate ERK1/2/Akt signaling; PSMD9 knockdown sensitizes to erlotinib
PMID: 38745188
4
PSMD9 is part of an MLXIPe/KHSRP/PSMD9 regulatory complex involved in bone metastatic prostate cancer radiotherapy resistance
PMID: 36632223
5
Higher serum PSMD9 levels associated with long-term benefits from immune checkpoint blockade in metastatic NSCLC patients
PMID: 39991958
6
PSMD9 is a multifunctional protein relying on protein-protein interactions with roles in proteasome assembly, cancer progression, and proteostasis
PMID: 41738541
7
PSMD9 identified as a risk factor for osteosarcopenia through multi-omics Mendelian randomization analysis
PMID: 41071635
8
PSMD9 is an assembly chaperone of the 26S proteasome modulator trimer complex; mapped to chromosome 12q24.2-q24.3
PMID: 9653651
Disease Associationsⓘ20
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
gastric cancerOpen Targets
0.10Weak
nasopharyngeal carcinomaOpen Targets
0.10Weak
osteosarcomaOpen Targets
0.10Suggestive
melanomaOpen Targets
0.09Suggestive
myocardial infarctionOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
lymphomaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
Miyoshi myopathyOpen Targets
0.09Suggestive
chronic lymphocytic leukemiaOpen Targets
0.08Suggestive
cholesteatomaOpen Targets
0.08Suggestive
chronic myelogenous leukemiaOpen Targets
0.08Suggestive
cervical cancerOpen Targets
0.08Suggestive
Uterine leiomyomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PSMD14Protein interaction100%PSMD12Protein interaction100%PSMD13Protein interaction100%PSMD10Protein interaction100%PSMD6Protein interaction100%ADRM1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
86%
Lung
66%
Ovary
65%
Brain
57%
Heart
53%
Gene Interaction Network
Click a node to explore
PSMD9PSMD14PSMD12PSMD13PSMD10PSMD6ADRM1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O00233
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.33LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.92 [0.65–1.33]
RankingsWhere PSMD9 stands among ~20K protein-coding genes
  • #2,796of 20,598
    Most Researched161 · top quartile
  • #13,913of 17,882
    Most Constrained (LOEUF)1.33
Genes detectedPSMD9
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
An integrative systems genetic analysis of mammalian lipid metabolism.
PMID: 30814737
Nature · 2019
1.00
2
Comprehensive analysis of PSMD family members and validation of PSMD9 as a potential therapeutic target in human glioblastoma.
PMID: 37485655
CNS Neurosci Ther · 2024
0.90
3
PSMD9 promotes the malignant progression of hepatocellular carcinoma by interacting with c-Cbl to activate EGFR signaling and recycling.
PMID: 38745188
J Exp Clin Cancer Res · 2024
0.80
4
Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by m
PMID: 36632223
Theranostics · 2023
0.70
5
Molecular and immunological features associated with long-term benefits in metastatic NSCLC patients undergoing immune checkpoint blockade.
PMID: 39991958
Oncoimmunology · 2025
0.60