PPIA Gene - Cyclophilin A
Peptidylprolyl Isomerase A: Structure, Function, and Clinical Relevance
Gene Information Card
| Symbol | PPIA |
|---|---|
| Full Name | Peptidylprolyl Isomerase A |
| Gene Type | Protein coding |
| Chromosomal Location | 7p13 |
| NCBI Gene ID | 5478 ncbi.nlm.nih.gov/gene/5478 |
| Ensembl ID | ENSG00000196262 |
| UniProt ID | P62937 |
| OMIM ID | 123840 |
| HGNC ID | 9253 |
| Aliases | CYPA, CYPH, cyclophilin A |
Description
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 Associations
| 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 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 68.2 | High |
| Lung | 55.3 | High |
| Heart | 42.1 | Medium |
| Liver | 38.7 | Medium |
| Kidney | 45.6 | Medium |
| Testis | 72.4 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 89.5 | Cervical cancer cell line |
| HEK293 | 76.2 | Embryonic kidney cells |
| A549 | 62.8 | Lung carcinoma |
| MCF7 | 55.1 | Breast cancer |
| Jurkat | 91.3 | T-cell leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123C>T (p.Ala41Val) | Missense | 0.001% (gnomAD) | Reduced binding to cyclosporine A; altered isomerase activity |
| c.456G>A (p.Arg152Gln) | Missense | 0.002% (gnomAD) | Unknown functional effect |
| c.789T>G (p.Asp263Glu) | Missense | 0.0005% (gnomAD) | Potential impact on protein stability |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported; homozygous knockout in mice is embryonic lethal.
Gain of Function (GOF)
Overexpression in cancer suggests gain-of-function role in proliferation and metastasis.
Dominant Negative (DN)
Not described for PPIA.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003755 - peptidyl-prolyl cis-trans isomerase activity | • GO:0006457 - protein folding |
| • GO:0043021 - ribonucleoprotein complex binding | • GO:0005515 - protein binding |
| • GO:0005737 - cytoplasm | • GO:0005634 - nucleus |
Pathways
• HIV Life Cycle (Reactome: R-HSA-162906)
• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)
• Apoptosis (KEGG: hsa04210)
Protein Summary
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.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPIAL4A Knockout HEK293 Cell Line | EDJ-KQ14104 | Human | 653505 | Details Get a Quote |
| PPIAL4C Knockout HEK293 Cell Line | EDJ-KQ14850 | Human | 653598 | Details Get a Quote |
| PPIAL4D Knockout HEK293 Cell Line | EDJ-KQ14851 | Human | 645142 | Details Get a Quote |
| PPIAL4E Knockout HEK293 Cell Line | EDJ-KQ14852 | Human | 730262 | Details Get a Quote |
| PPIAL4F Knockout HEK293 Cell Line | EDJ-KQ14853 | Human | 728945 | Details Get a Quote |
| PPIAL4H Knockout HEK293 Cell Line | EDJ-KQ14854 | Human | 105371242 | Details Get a Quote |
| PPIA Knockout HEK293 Cell Line | EDJ-KQ50531 | Human | 5478 | Details Get a Quote |
| PPIAL4G Knockout HEK293 Cell Line | EDJ-KQ52382 | Human | 644591 | Details Get a Quote |
| PPIA Knockout HeLa Cell Line | EDJ-KQ54190 | Human | 5478 | Details Get a Quote |
| PPIAL4G Knockout HeLa Cell Line | EDJ-KQ60572 | Human | 644591 | Details Get a Quote |
| PPIAL4D Knockout HeLa Cell Line | EDJ-KQ60582 | Human | 645142 | Details Get a Quote |
| PPIAL4A Knockout HeLa Cell Line | EDJ-KQ60650 | Human | 653505 | Details Get a Quote |
| PPIAL4C Knockout HeLa Cell Line | EDJ-KQ60654 | Human | 653598 | Details Get a Quote |
| PPIAL4F Knockout HeLa Cell Line | EDJ-KQ60727 | Human | 728945 | Details Get a Quote |
| PPIAL4E Knockout HeLa Cell Line | EDJ-KQ60775 | Human | 730262 | Details Get a Quote |
Displaying Records 1 To 15 Of 30 Records
