Ppif (Peptidylprolyl Isomerase F)
Cyclophilin D: Mitochondrial Permeability Transition Pore Regulator
Gene Information Card
| Symbol | Ppif |
|---|---|
| Full Name | Peptidylprolyl isomerase F |
| Gene Type | protein-coding |
| Chromosomal Location | 14q22.1 |
| NCBI Gene ID | 10105 ncbi.nlm.nih.gov/gene/10105 |
| Ensembl ID | ENSG00000100697 |
| UniProt ID | P30405 |
| OMIM ID | 604486 |
| HGNC ID | 9259 |
| Aliases | Cyp-D, cyclophilin D, CYP3, PPIF |
Description
The Ppif gene encodes cyclophilin D (CypD), a mitochondrial matrix peptidylprolyl isomerase that regulates the mitochondrial permeability transition pore (MPTP). CypD modulates calcium-induced mitochondrial swelling, apoptosis, and necrosis. It is implicated in ischemia-reperfusion injury, neurodegenerative diseases, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ischemia-reperfusion injury | CypD-mediated MPTP opening leads to mitochondrial dysfunction and cell death | PMID: 15665853, 19043405 |
| Alzheimer disease | Increased CypD expression enhances MPTP opening, contributing to mitochondrial dysfunction and synaptic damage | PMID: 19043405, 21278726 |
| Muscular dystrophy (collagen VI-related) | CypD-dependent MPTP dysregulation causes mitochondrial dysfunction in muscle cells | PMID: 20037584 |
| Cancer (various) | CypD modulates apoptosis resistance; overexpression in some tumors linked to chemoresistance | PMID: 25944712, 28445460 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 15.2 | Medium |
| Brain | 8.7 | Low |
| Liver | 12.1 | Medium |
| Skeletal Muscle | 18.5 | Medium |
| Kidney | 10.3 | Medium |
| Pancreas | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.5 | High expression |
| HeLa | 11.2 | Medium expression |
| HepG2 | 9.8 | Medium expression |
| SH-SY5Y | 7.3 | Low expression |
| K562 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.256C>T (p.Arg86Trp) | Missense | <0.01% | Alters cyclophilin D structure; potential effect on MPTP regulation |
| c.389G>A (p.Arg130His) | Missense | <0.01% | Reported in ClinVar; uncertain significance |
| c.472C>T (p.Arg158Cys) | Missense | <0.01% | Rare variant; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in human disease; knockout mouse models show resistance to MPTP opening and ischemia-reperfusion injury.
Gain of Function (GOF)
No confirmed gain-of-function mutations; overexpression studies suggest increased MPTP sensitivity.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity (GO:0003755) | • cyclosporin A binding (GO:0016018) |
| • mitochondrial matrix (GO:0005759) | • protein folding (GO:0006457) |
| • regulation of mitochondrial membrane permeability (GO:0098856) | • apoptotic process (GO:0006915) |
Pathways
• Mitochondrial permeability transition pore (MPTP) opening
• Apoptosis - intrinsic pathway
• Necrosis signaling
• Unfolded protein response (UPRmt)
Protein Summary
Cyclophilin D (CypD) is a 207-amino acid mitochondrial matrix protein with peptidylprolyl cis-trans isomerase (PPIase) activity. It binds to the adenine nucleotide translocator (ANT) and other MPTP components, facilitating pore opening in response to calcium and oxidative stress. CypD is inhibited by cyclosporin A. It plays a key role in cell death decisions, particularly in ischemia-reperfusion injury and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPIF Knockout HEK293 Cell Line | EDJ-KQ1630 | Human | 10105 | Details Get a Quote |
| PPIF Knockout A-549 Cell Line | EDJ-KQ21343 | Human | 10105 | Details Get a Quote |
| PPIF Knockout HCT 116 Cell Line | EDJ-KQ21344 | Human | 10105 | Details Get a Quote |
| PPIF Knockout HeLa Cell Line | EDJ-KQ21345 | Human | 10105 | Details Get a Quote |
| PPIF Knockout Caco-2 Cell Line | EDJ-KZ409 | Human | 10105 | Details Get a Quote |
| Ppif Knockout AML12 Cell Line | EDC07702 | Mouse | 105675 | Details Get a Quote |
| PPIF Knockout THLE-2 Cell Line | EDC07850 | Human | 10105 | Details Get a Quote |
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