PPIA
protein-codingpeptidylprolyl isomerase A, the group of Cyclophilin peptidylprolyl isomerases
Gene summary
This gene encodes 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. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [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 ~27.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0004976
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPIA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021130.5. 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 | 0 | |||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 6 | 0 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066953.1 | 5 | MANE Select | |
| Ensembl | ENSP00000419425.1 | 5 | MANE Select | |
| RefSeq | NP_001287910.1 | 3 | Standard | |
| Ensembl | ENSP00000430817.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Necroptosis - Homo sapiens (human)
- Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
- Prolactin Signaling Pathway
- JAK-STAT
- Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
Biological Process
- protein peptidyl-prolyl isomerization
- RNA-dependent DNA biosynthetic process
- protein folding
- viral life cycle
- uncoating of virus
Molecular Function
- RNA binding
- peptidyl-prolyl cis-trans isomerase activity
- protein binding
- cyclosporin A binding
- virion binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- cytosol
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000468812
- Coding exons
- 5
- Length
- 27885
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125740
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.99 | 41 | 95.8 | 0.428 | 0.00000476 | 1103 |
| Missense (PolyPhen) | 0 | 7.8066 | 0 | 134 | ||
| Synonymous | -0.00226 | 34 | 34.0 | 1.00 | 0.00000163 | 302 |
| Loss of Function | 2.03 | 1 | 6.65 | 0.150 | 2.78e-7 | 88 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269|PubMed:20676357}.;
Recessive Scores
- pRec
- 0.413
Intolerance Scores
- LoFtool
- 0.296
- RVIS EVS
- 0.06
- RVIS percentile EVS
- 58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |