PPIF
protein-codingpeptidylprolyl isomerase F, the group of Cyclophilin peptidylprolyl isomerases
Gene summary
The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be involved in the induction of apoptotic and necrotic cell death. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPIF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005729.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 35 | 35 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 36 | 0 | 2 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005720.1 | 6 | MANE Select | |
| Ensembl | ENSP00000225174.3 | 6 | MANE Select | |
| Ensembl | ENSP00000396388.1 | 6 | Standard | |
| Ensembl | ENSP00000473548.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Huntington,s disease - Homo sapiens (human)
- Calcium signaling pathway - Homo sapiens (human)
- Toxoplasmosis - Homo sapiens (human)
- Parkinson,s disease - Homo sapiens (human)
- cGMP-PKG signaling pathway - Homo sapiens (human)
Biological Process
- protein peptidyl-prolyl isomerization
- response to ischemia
- protein folding
- regulation of proton-transporting ATPase activity, rotational mechanism
- negative regulation of ATPase activity
Molecular Function
- peptidyl-prolyl cis-trans isomerase activity
- protein binding
- cyclosporin A binding
- unfolded protein binding
Cellular Component
- mitochondrion
- mitochondrial proton-transporting ATP synthase complex
- mitochondrial permeability transition pore complex
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225174
- Coding exons
- 6
- Length
- 7869
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 67
- Defined
- 125748
- p
- 0.000266
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.676 | 88 | 108 | 0.817 | 0.00000610 | 1335 |
| Missense (PolyPhen) | 47 | 53.915 | 0.87174 | 599 | ||
| Synonymous | 0.916 | 38 | 45.9 | 0.828 | 0.00000305 | 420 |
| Loss of Function | 0.909 | 5 | 7.73 | 0.647 | 3.27e-7 | 98 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.0012 | 0.0012 | notable |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis. {ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735}.;
Recessive Scores
- pRec
- 0.199
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.938
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |