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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PPIC
peptidylprolyl isomerase C
Chromosome 5 · 5q23.2
NCBI Gene: 5480Ensembl: ENSG00000168938.7HGNC: HGNC:9256UniProt: P45877
40PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
peptidyl-prolyl cis-trans isomerase activityprotein bindingextracellular exosomeprotein foldingdiverticular diseaseocular hypotensioncoronary atherosclerosisInguinal hernia
✦AI Summary

PPIC (peptidylprolyl isomerase C) is a peptidyl-prolyl cis-trans isomerase that catalyzes protein folding by facilitating the isomerization of proline residues in peptide bonds 1. The protein functions as a molecular chaperone, with all cyclophilin family members, including PPIC, demonstrating the ability to prevent tau aggregation in vitro, with PPIC showing particularly strong inhibitory effects 1. In cellular models, PPIC reduces both soluble and insoluble tau levels and uniquely protects cells from tau seeding, suggesting neuroprotective potential in tauopathies 1. However, PPIC also exhibits pathological roles in multiple diseases. In hepatic fibrosis, PPIC expression is upregulated and promotes hepatic stellate cell activation and extracellular matrix deposition, with knockdown significantly improving liver damage in mouse models 2. PPIC expression is regulated by miR-137-3p, forming a regulatory axis that modulates hepatic fibrosis progression 2. In cancer contexts, PPIC serves as a prognostic biomarker, with upregulation associated with poor outcomes in high-grade gliomas 3 and cutaneous melanoma, where it promotes tumor progression and drug resistance while suppressing CD8+ T cell activation 4. PPIC is also identified as a key predictive gene in idiopathic pulmonary fibrosis, potentially co-regulating NOTCH and autophagy pathways 5.

Sources cited
1
PPIC prevents tau aggregation and reduces cellular tau accumulation, with unique protective effects against tau seeding
PMID: 36305768
2
PPIC promotes hepatic stellate cell activation and fibrosis, regulated by miR-137-3p
PMID: 34224798
3
PPIC is associated with poor prognosis in melanoma and promotes tumor progression while suppressing immune responses
PMID: 39115044
4
PPIC is upregulated in glioma tissue and correlates with patient survival as a prognostic marker
PMID: 27801851
5
PPIC is identified as a key predictive gene in idiopathic pulmonary fibrosis, potentially regulating NOTCH and autophagy pathways
PMID: 40494203
Disease Associationsⓘ20
diverticular diseaseOpen Targets
0.26Weak
ocular hypotensionOpen Targets
0.13Weak
coronary atherosclerosisOpen Targets
0.12Weak
Inguinal herniaOpen Targets
0.11Weak
coronary artery diseaseOpen Targets
0.10Weak
androgenetic alopeciaOpen Targets
0.08Suggestive
hypertensionOpen Targets
0.08Suggestive
migraine disorderOpen Targets
0.08Suggestive
essential hypertensionOpen Targets
0.08Suggestive
Genu valgumOpen Targets
0.08Suggestive
ovarian neoplasmOpen Targets
0.08Suggestive
Genu varumOpen Targets
0.06Suggestive
cardiovascular diseaseOpen Targets
0.05Suggestive
Increased blood pressureOpen Targets
0.05Suggestive
alopeciaOpen Targets
0.05Suggestive
neutropenia, severe congenital, 2, autosomal dominantOpen Targets
0.05Suggestive
thoracic aortic aneurysmOpen Targets
0.04Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.04Suggestive
Abnormal nasolacrimal system morphologyOpen Targets
0.04Suggestive
aneurysmOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PPIAL4HShared pathway100%SDIM1Shared pathway100%PPIAL4EShared pathway100%PPIAL4FShared pathway100%PPIAL4CShared pathway100%PPIAL4AShared pathway100%
Tissue Expression6 tissues
Heart
100%
Liver
53%
Lung
45%
Ovary
31%
Brain
5%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
PPICPPIAL4HSDIM1PPIAL4EPPIAL4FPPIAL4CPPIAL4A
PROTEIN STRUCTURE
Preparing viewer…
PDB2ESL · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.35LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.62–1.35]
RankingsWhere PPIC stands among ~20K protein-coding genes
  • #10,224of 20,598
    Most Researched40
  • #14,151of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedPPIC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The prognostic implications of cuproptosis-related gene signature and the potential of PPIC as a promising biomarker in cutaneous melanoma.
PMID: 39115044
Pigment Cell Melanoma Res · 2024
1.00
2
Ppic modulates CCl
PMID: 34224798
Toxicol Lett · 2021
0.90
3
Chaperoning activity of the cyclophilin family prevents tau aggregation.
PMID: 36305768
Protein Sci · 2022
0.80
4
Machine learning algorithms integrate bulk and single-cell RNA data to reveal the crosstalk and heterogeneity of NOTCH and autophagy activity following idiopathic pulmonary fibrosis.
PMID: 40494203
Int Immunopharmacol · 2025
0.70
5
Polymersomal Poly(I:C) Self-Magnifies Antitumor Immunity by Inducing Immunogenic Cell Death and Systemic Immune Activation.
PMID: 38896790
Adv Healthc Mater · 2024
0.60