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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP4C
protein phosphatase 4 catalytic subunit
Chromosome 16 · 16p11.2
NCBI Gene: 5531Ensembl: ENSG00000149923.15HGNC: HGNC:9319UniProt: A0A024R625
117PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Homologous Recombination
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein serine/threonine phosphatase activitychromatinnucleoplasmprotein bindingneurodegenerative diseaseneoplasmlung adenocarcinomabreast cancer
✦AI Summary

PPP4C (protein phosphatase 4 catalytic subunit) is a serine/threonine phosphatase with diverse cellular functions centered on DNA damage response and cell cycle regulation. Primary functions include dephosphorylation of key DNA repair proteins—PPP4C dephosphorylates gamma-H2AX and RPA2 to facilitate homologous recombination repair 1, and dephosphorylates PLK1 to negatively regulate its activity during DSB response 1. The enzyme regulates multiple signaling pathways including NF-κB and STAT1 activation 2, and modulates YAP1 activity through MST4 dephosphorylation 3. Clinically, PPP4C overexpression is associated with poor prognosis across multiple cancer types. High PPP4C expression in gastric cancer promotes cell cycle progression by inhibiting p53 signaling, increasing S-phase cells and alleviating G2/M arrest 4. In lung adenocarcinoma, elevated PPP4C correlates with poor survival and promotes tumor proliferation and migration 5. Similarly, high PPP4C expression predicts poor overall and progression-free survival in diffuse large B-cell lymphoma 6. Conversely, PPP4C inhibition sensitizes ovarian cancer to immune attack by activating inflammatory signaling and enhancing NK cell cytotoxicity 2. Non-neoplastic functions include male fertility—PPP4C deficiency causes oligoasthenoteratospermia-like phenotypes in mice 7. These findings position PPP4C as both a prognostic biomarker and potential therapeutic target.

Sources cited
1
High PPP4C expression in gastric cancer promotes malignant progression and is an independent risk factor for poor 5-year survival; promotes cell proliferation by inhibiting p53 signaling
PMID: 37927012
2
PP4 inhibition combined with carboplatin triggers inflammatory signaling via NF-κB and STAT1 activation, enhancing NK cell-mediated cytotoxicity against ovarian cancer cells
PMID: 36564125
3
Elevated PPP4C expression in lung adenocarcinoma correlates with poor prognosis and promotes cellular proliferation and migration; associated with altered immune microenvironment
PMID: 39026674
4
PPP4C deletion in mice causes male-specific infertility with oligoasthenoteratospermia-like features including sperm tail bending, low sperm count, and poor motility
PMID: 33543287
5
PPP4C dephosphorylates and inactivates MST4, promoting YAP1 activation and enhancing tumor growth and immunosuppression in NSCLC
PMID: 41690452
6
High PPP4C expression in diffuse large B-cell lymphoma predicts poor overall survival and progression-free survival as an independent prognostic factor
PMID: 38683255
7
PPP4C dephosphorylates PLK1 at S137 to negatively regulate its activity during DNA damage response; deletion causes female subfertility due to DNA damage accumulation
PMID: 35546066
8
PPP4C regulatory subunits interact with the catalytic subunit to control activity in organelle assembly, spliceosomal assembly, DNA damage response, and chromatin regulation
PMID: 15913612
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.43Moderate
neoplasmOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
Insulin resistanceOpen Targets
0.08Suggestive
diffuse large B-cell lymphomaOpen Targets
0.07Suggestive
substance-related disorderOpen Targets
0.07Suggestive
cancerOpen Targets
0.04Suggestive
Crigler-Najjar syndrome type 2Open Targets
0.04Suggestive
cholestasis, progressive familial intrahepatic, 11Open Targets
0.03Suggestive
colitisOpen Targets
0.03Suggestive
gliomaOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
SepsisOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.02Suggestive
Mobius syndromeOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
ovarian cancerOpen Targets
0.01Suggestive
adrenal cortex carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes

No related genes found for this gene.

Tissue Expression6 tissues
Liver
100%
Lung
93%
Bone Marrow
75%
Heart
46%
Ovary
44%
Brain
41%
Gene Interaction Network

No interaction data available for this gene.

PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P60510
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.15–0.41]
RankingsWhere PPP4C stands among ~20K protein-coding genes
  • #4,062of 20,598
    Most Researched117 · top quartile
  • #2,106of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedPPP4C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
[Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer].
PMID: 37927012
Zhongguo Yi Xue Ke Xue Yuan Xue Bao · 2023
1.00
2
PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling.
PMID: 36564125
J Immunother Cancer · 2022
0.90
3
Comprehensive analysis of PPP4C's impact on prognosis, immune microenvironment, and immunotherapy response in lung adenocarcinoma using single-cell sequencing and multi-omics.
PMID: 39026674
Front Immunol · 2024
0.80
4
Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice.
PMID: 33543287
Mol Hum Reprod · 2021
0.70
5
PPP4C restores YAP1 activity by modulating MST4 phosphorylation to enhance immunosuppression and augment tumor growth in non-small cell lung cancer.
PMID: 41690452
Cancer Lett · 2026
0.60