PPIA Gene: Cyclophilin A - Function, Mutations, and Disease Associations

The PPIA gene encodes cyclophilin A, a member of the cyclophilin family of peptidylprolyl isomerases. Cyclophilin A catalyzes the cis-trans isomerization of proline peptide bonds, facilitating protein folding and trafficking. It is the intracellular receptor for the immunosuppressive drug cyclosporine A and plays roles in HIV-1 replication, inflammation, and cancer progression.

Disease category	Pathophysiological mechanism	Genomic evidence
HIV-1 Infection	PPIA binds HIV-1 capsid protein, facilitating viral uncoating and replication; cyclosporine A inhibits this interaction.	PMID: 10623723
Cardiovascular Disease	Cyclophilin A secreted by vascular smooth muscle cells promotes inflammation and oxidative stress in atherosclerosis.	PMID: 15044694
Cancer (multiple types)	Overexpression of PPIA in various cancers (e.g., lung, breast, pancreatic) correlates with poor prognosis; promotes cell proliferation and metastasis.	PMID: 29351289
Rheumatoid Arthritis	Elevated cyclophilin A levels in synovial fluid contribute to inflammatory cytokine production.	PMID: 16914746

Cyclophilin A (UniProt P62937) is a 165-amino acid protein with a molecular weight of 18 kDa. It possesses peptidyl-prolyl cis-trans isomerase activity essential for protein folding. It is ubiquitously expressed and localized mainly in the cytoplasm but can also be secreted under stress conditions. It binds cyclosporine A, forming a complex that inhibits calcineurin, thereby suppressing T-cell activation. In HIV-1 infection, cyclophilin A is incorporated into virions and is required for efficient viral replication. Elevated levels are associated with various cancers and inflammatory diseases.