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GeneE
5 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP4R4
protein phosphatase 4 regulatory subunit 4
Chromosome 14 · 14q32.12-q32.13
NCBI Gene: 57718Ensembl: ENSG00000119698.13HGNC: HGNC:23788UniProt: Q6NUP7
23PubMed Papers
0Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein phosphatase inhibitor activityprotein serine/threonine phosphatase inhibitor activityprotein bindingcytoplasm
✦AI Summary

PPP4R4 (protein phosphatase 4 regulatory subunit 4) is a regulatory subunit that forms a novel stable cytosolic complex with the catalytic subunit of protein phosphatase 4 (PP4c) 1. Unlike the scaffolding role of PP2A regulatory subunits, PPP4R4 associates specifically with PP4c but does not bridge it with other characterized PP4 regulatory subunits, representing an independent regulatory mechanism 1. The PP4c-PPP4R4 complex exhibits phosphatase activity toward fluorogenic substrates and the DNA damage marker gammaH2AX, though with lower activity than other PP4 regulatory protein combinations 1. PP4c participates in critical cellular processes including microtubule organization, DNA damage checkpoint recovery, and apoptosis regulation 1. PPP4R4 expression is dysregulated in disease contexts: it was identified as downregulated in FASN-silenced osteosarcoma cells 2, as a target of smoking-related microRNA hsa-miR-627-5p in airway epithelium 3, and associated with severe chr14 obstructive pulmonary disease (COPD) risk loci 4. These findings suggest PPP4R4 plays roles in phosphatase regulation, lung disease pathogenesis, and potentially cancer development, though direct functional characterization in disease contexts remains limited.

Sources cited
1
PPP4R4 forms a novel stable cytosolic complex with PP4c; exhibits phosphatase activity toward fluorogenic substrates and gammaH2AX; represents independent regulatory mechanism distinct from other PP4 complexes
PMID: 18715871
2
PPP4R4 is downregulated in FASN-silenced osteosarcoma 143B cells
PMID: 33405298
3
PPP4R4 is a target gene of smoking-related microRNA hsa-miR-627-5p in human airway epithelium
PMID: 31568004
4
SNPs near PPP4R4/SERPINA1 are significantly associated with severe COPD (P = 1.01 × 10-8)
PMID: 28170284
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPP4R2Protein interaction100%PPP4CProtein interaction98%PPP4R1Protein interaction98%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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PPP4R4PPP4R2PPP4CPPP4R1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q6NUP7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.43–0.71]
RankingsWhere PPP4R4 stands among ~20K protein-coding genes
  • #13,491of 20,598
    Most Researched23
  • #5,497of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedPPP4R4
Sources retrieved5 papers
Response time—
📄 Sources
5
1
Identification of gene and microRNA changes in response to smoking in human airway epithelium by bioinformatics analyses.
PMID: 31568004
Medicine (Baltimore) · 2019
1.00
2
iTRAQ-based proteomic analysis of the molecular mechanisms and downstream effects of fatty acid synthase in osteosarcoma cells.
PMID: 33405298
J Clin Lab Anal · 2021
0.80
3
Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.
PMID: 28170284
Am J Respir Cell Mol Biol · 2017
0.60
4
Natural Antioxidant By-Product Mixture Counteracts the Effects of Aflatoxin B1 and Ochratoxin A Exposure of Piglets after Weaning: A Proteomic Survey on Liver Microsomal Fraction.
PMID: 37104237
Toxins (Basel) · 2023
0.40
5
PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4.
PMID: 18715871
J Biol Chem · 2008
0.20