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GeneE
4 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP4R3B
protein phosphatase 4 regulatory subunit 3B
Chromosome 2 · 2p16.1
NCBI Gene: 57223Ensembl: ENSG00000275052.6HGNC: HGNC:29267UniProt: Q5MIZ7
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
centrosomenuclear speckregulation of double-strand break repairnucleoplasmhypothyroidismmale reproductive organ cancerhypertensionessential hypertension
✦AI Summary

PPP4R3B is a regulatory subunit of protein phosphatase 4 (PP4), a critical regulator of DNA damage response (DDR) and immune signaling. As a component of the PP4 complex, PPP4R3B likely modulates serine/threonine phosphatase activity at centrosomal and nuclear sites, influencing double-strand break repair and chr2 dynamics 1. Functionally, PPP4R3B participates in coordinating cellular responses to DNA damage and genotoxic stress. PP4 inhibition or PPP4R3B knockdown combined with chemotherapy triggers robust inflammatory signaling through NF-κB and STAT1 activation, increasing pro-inflammatory cytokine expression (CCL5, CXCL10, IL-6) and type I interferon responses 1. These events enhance recruitment and activation of immune effector cells, including NK cells and CD8+ T cells, promoting anti-tumor immunity 1. Clinically, PPP4R3B dysfunction has been associated with psoriasis susceptibility, identified through exome-wide rare loss-of-function variant analysis in Han Chinese populations 2. The gene's role in both cancer immunotherapy and inflammatory disease suggests PPP4R3B functions as a nodal regulator integrating DNA damage signals with immune activation pathways. These findings support investigating PP4/PPP4R3B inhibition as a potential therapeutic strategy to enhance chemo-immunotherapy responses in ovarian cancer and other malignancies.

Sources cited
1
PPP4R3B knockdown combined with chemotherapy triggers STAT1/NF-κB inflammatory signaling, increases pro-inflammatory cytokines and type I interferon response, and enhances NK cell and CD8+ T cell recruitment and anti-tumor cytotoxicity
PMID: 36564125
2
PPP4R3B is identified as a susceptibility gene for psoriasis via rare loss-of-function variant enrichment study in Han Chinese populations
PMID: 31376382
3
PPP4R3B-DT (a cuproptosis-related lncRNA) functions as a protective factor in predicting prognosis of NSCLC patients after radiotherapy
PMID: 36360316
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
hypothyroidismOpen Targets
0.39Weak
male reproductive organ cancerOpen Targets
0.30Weak
hypertensionOpen Targets
0.29Weak
essential hypertensionOpen Targets
0.29Weak
VitiligoOpen Targets
0.26Weak
myxedemaOpen Targets
0.20Weak
thyroid diseaseOpen Targets
0.17Weak
autoimmune thyroid diseaseOpen Targets
0.16Weak
MODYOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.05Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.05Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
maturity-onset diabetes of the young type 2Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.05Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPP4R3AProtein interaction100%PPP4R3CProtein interaction99%PPP2CAProtein interaction99%CRTC2Protein interaction92%PPP3CAProtein interaction91%RANBP1Protein interaction76%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
90%
Brain
85%
Ovary
67%
Lung
66%
Heart
60%
Gene Interaction Network
Click a node to explore
PPP4R3BPPP4R3APPP4R3CPPP2CACRTC2PPP3CARANBP1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q5MIZ7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.80LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.61 [0.47–0.80]
RankingsWhere PPP4R3B stands among ~20K protein-coding genes
  • #8,480of 20,598
    Most Researched53
  • #6,695of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedPPP4R3B
Sources retrieved4 papers
Response time—
📄 Sources
4
1
PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling.
PMID: 36564125
J Immunother Cancer · 2022
1.00
2
Radiosensitization-Related Cuproptosis LncRNA Signature in Non-Small Cell Lung Cancer.
PMID: 36360316
Genes (Basel) · 2022
0.75
3
Exome-Wide Rare Loss-of-Function Variant Enrichment Study of 21,347 Han Chinese Individuals Identifies Four Susceptibility Genes for Psoriasis.
PMID: 31376382
J Invest Dermatol · 2020
0.50
4
Rbm38 Reduces the Transcription Elongation Defect of the
PMID: 33233740
Int J Mol Sci · 2020
0.25