PPID Gene - Cyclophilin D
PPID (Peptidylprolyl Isomerase D) encodes cyclophilin D, a mitochondrial peptidyl-prolyl cis-trans isomerase involved in mitochondrial permeability transition pore regulation.
Gene Information Card
| Symbol | PPID |
|---|---|
| Full Name | Peptidylprolyl Isomerase D |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.3 |
| NCBI Gene ID | 5481 ncbi.nlm.nih.gov/gene/5481 |
| Ensembl ID | ENSG00000138684 |
| UniProt ID | Q08752 |
| OMIM ID | 601753 |
| HGNC ID | 9258 |
| Aliases | CYP40, CYPD, cyclophilin D |
Description
PPID (Peptidylprolyl Isomerase D) is a protein-coding gene located on chromosome 4q31.3. It encodes cyclophilin D, a member of the cyclophilin family of peptidyl-prolyl cis-trans isomerases. Cyclophilin D is primarily localized to the mitochondrial matrix and plays a critical role in regulating the mitochondrial permeability transition pore (mPTP). By modulating mPTP opening, cyclophilin D influences mitochondrial membrane potential, calcium homeostasis, and cell death pathways, particularly in the context of ischemia-reperfusion injury and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ischemia-reperfusion injury | Cyclophilin D promotes mPTP opening, leading to mitochondrial swelling and cell death during reperfusion | PMID: 15775970 |
| Alzheimer disease | Increased cyclophilin D expression enhances mPTP opening and mitochondrial dysfunction in neurons | PMID: 18425119 |
| Muscular dystrophy (Duchenne) | Cyclophilin D-mediated mPTP opening contributes to muscle cell death in dystrophin-deficient models | PMID: 20037584 |
| Multiple sclerosis | Cyclophilin D inhibition reduces axonal degeneration in experimental autoimmune encephalomyelitis | PMID: 23934111 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Brain | 8.7 | Low |
| Liver | 6.2 | Low |
| Skeletal muscle | 15.1 | Medium |
| Kidney | 9.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Cervical carcinoma |
| HEK293 | 8.2 | Embryonic kidney |
| SH-SY5Y | 7.9 | Neuroblastoma |
| HepG2 | 6.8 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | Unknown functional effect |
| c.100C>T | Nonsense | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., c.100C>T) are predicted to cause loss of cyclophilin D function, potentially reducing mPTP opening and protecting against cell death.
Gain of Function (GOF)
No gain-of-function mutations have been reported in PPID.
Dominant Negative (DN)
No dominant-negative mutations have been described for PPID.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity (GO:0003755) | • mitochondrion (GO:0005739) |
| • apoptotic process (GO:0006915) | • unfolded protein binding (GO:0051082) |
| • protein folding (GO:0006457) |
Pathways
• Mitochondrial permeability transition pore (mPTP) regulation
• Apoptosis - intrinsic pathway
Protein Summary
Cyclophilin D (CypD) is a 207-amino acid protein (UniProt Q08752) localized to the mitochondrial matrix. It possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity, which catalyzes the isomerization of proline peptide bonds. CypD binds to the adenine nucleotide translocator (ANT) and other mPTP components, promoting pore opening under stress conditions such as elevated calcium and oxidative stress. This activity is central to mitochondrial permeability transition, a key event in necrotic and apoptotic cell death. CypD is a target of the immunosuppressant drug cyclosporin A, which inhibits its PPIase activity and blocks mPTP opening.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPID Knockout HEK293 Cell Line | EDJ-KQ3707 | Human | 5481 | Details Get a Quote |
| PPID Knockout A-549 Cell Line | EDJ-KQ25731 | Human | 5481 | Details Get a Quote |
| PPID Knockout HCT 116 Cell Line | EDJ-KQ25732 | Human | 5481 | Details Get a Quote |
| PPID Knockout HeLa Cell Line | EDJ-KQ25733 | Human | 5481 | Details Get a Quote |
