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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPP5C
protein phosphatase 5 catalytic subunit
Chromosome 19 · 19q13.32
NCBI Gene: 5536Ensembl: ENSG00000011485.16HGNC: HGNC:9322UniProt: P53041
149PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA Repair
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Hsp90 protein bindingprotein-containing complexprotein folding chaperone complexpeptidyl-serine dephosphorylationCrohn's diseaseatrial fibrillationulcerative colitisankylosing spondylitis
✦AI Summary

PPP5C encodes protein phosphatase 5 (PP5), a serine/threonine protein phosphatase with dual function as both a phosphatase and co-chaperone 1. The enzyme exhibits unique self-inhibitory regulation through low basal activity that is activated by various cellular signals 1. PPP5C functions as a catalytic phosphatase by coordinating with active-site metal ions and dephosphorylating diverse substrates including kinases, nuclear receptors, and signaling proteins 2. The protein regulates multiple cellular processes including cell cycle progression, apoptosis, and signaling pathways such as Wnt signaling through dephosphorylation of Dvl2 3. PPP5C is highly expressed in several cancer types including prostate, bladder, and ovarian cancers, where it promotes cell proliferation and survival 456. In prostate cancer, PPP5C regulates JNK and ERK1/2 phosphorylation to promote cell survival 4. The gene shows intolerance to loss-of-function variants, and de novo variants cause severe developmental phenotypes including microcephaly, seizures, and developmental delay, suggesting haploinsufficiency 7. PPP5C also participates in glucocorticoid-responsive gene networks in brain tissue, contributing to stress response mechanisms 8. Its dual phosphatase-chaperone function makes PPP5C an emerging therapeutic target for cancer treatment 1.

Sources cited
1
PPP5C has dual function as phosphatase and co-chaperone with self-inhibitory regulation
PMID: 37054560
2
PPP5C is a catalytic phosphatase that coordinates with active-site metal ions
PMID: 30679389
3
PPP5C regulates Wnt signaling through dephosphorylation of Dvl2
PMID: 29426949
4
PPP5C is highly expressed in prostate cancer and regulates JNK/ERK phosphorylation
PMID: 30254472
5
PPP5C is highly expressed in bladder cancer and promotes proliferation
PMID: 28534961
6
PPP5C promotes ovarian cancer cell proliferation and colony formation
PMID: 26870184
7
De novo PPP5C variants cause microcephaly, seizures, and developmental delay via haploinsufficiency
PMID: 35361529
8
PPP5C participates in glucocorticoid-responsive gene networks in brain
PMID: 29180230
Disease Associationsⓘ20
Crohn's diseaseOpen Targets
0.41Moderate
atrial fibrillationOpen Targets
0.37Weak
ulcerative colitisOpen Targets
0.30Weak
ankylosing spondylitisOpen Targets
0.29Weak
sclerosing cholangitisOpen Targets
0.29Weak
psoriasisOpen Targets
0.28Weak
neurodegenerative diseaseOpen Targets
0.26Weak
neuroinflammatory disorderOpen Targets
0.20Weak
Neurodevelopmental disorderOpen Targets
0.12Weak
Oral ulcerOpen Targets
0.12Weak
autism spectrum disorderOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.07Suggestive
astrocytomaOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
oligodendrogliomaOpen Targets
0.07Suggestive
ParagangliomaOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
clear cell adenocarcinomaOpen Targets
0.06Suggestive
myelodysplastic syndromeOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
LB-100Phase II
Serine/threonine-protein phosphatase 5 inhibitor
astrocytoma
Related Genes
HSP90AA1Protein interaction100%HSP90AB1Protein interaction100%CDC37Protein interaction100%PTGES3Protein interaction99%BRAFProtein interaction98%MAP3K5Protein interaction97%
Tissue Expression6 tissues
Heart
100%
Lung
63%
Ovary
62%
Liver
62%
Brain
57%
Bone Marrow
36%
Gene Interaction Network
Click a node to explore
PPP5CHSP90AA1HSP90AB1CDC37PTGES3BRAFMAP3K5
PROTEIN STRUCTURE
Preparing viewer…
PDB4ZX2 · 1.23 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.46Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.32 [0.22–0.46]
RankingsWhere PPP5C stands among ~20K protein-coding genes
  • #3,047of 20,598
    Most Researched149 · top quartile
  • #2,561of 17,882
    Most Constrained (LOEUF)0.46 · top quartile
Genes detectedPPP5C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Glucocorticoids, genes and brain function.
PMID: 29180230
Prog Neuropsychopharmacol Biol Psychiatry · 2018
1.00
2
PPP5C promotes cell proliferation and survival in human prostate cancer by regulating of the JNK and ERK1/2 phosphorylation.
PMID: 30254472
Onco Targets Ther · 2018
0.90
3
Dual function of protein phosphatase 5 (PPP5C): An emerging therapeutic target for drug discovery.
PMID: 37054560
Eur J Med Chem · 2023
0.80
4
The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.
PMID: 30679389
Mol Cancer Ther · 2019
0.70
5
Disruption of serine/threonine protein phosphatase 5 inhibits tumorigenesis of urinary bladder cancer cells.
PMID: 28534961
Int J Oncol · 2017
0.60