PPIL2
protein-codingpeptidylprolyl isomerase like 2, the group of Spliceosomal Bact complex|Cyclophilin peptidylprolyl isomerases|U-box domain containing
Gene summary
This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.0 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 PPIL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014337.4. 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 | 4 | 1 | 5 | |||
| missense | 94 | 2 | 96 | |||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 105 | 3 | 1 | 109 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055152.1 | 20 | MANE Select | |
| Ensembl | ENSP00000381812.3 | 20 | MANE Select | |
| RefSeq | NP_001304925.1 | 20 | Standard | |
| RefSeq | NP_680480.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Cell surface interactions at the vascular wall
- Hemostasis
- Basigin interactions
Biological Process
- protein polyubiquitination
- protein peptidyl-prolyl isomerization
- protein folding
- leukocyte migration
- protein localization to plasma membrane
Molecular Function
- peptidyl-prolyl cis-trans isomerase activity
- protein binding
- cyclosporin A binding
- ubiquitin-ubiquitin ligase activity
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- Golgi lumen
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412327
- Coding exons
- 21
- Length
- 47746
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 81
- Defined
- 125748
- p
- 0.000326
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.64 | 247 | 331 | 0.746 | 0.0000204 | 3487 |
| Missense (PolyPhen) | 61 | 106.45 | 0.57304 | 1136 | ||
| Synonymous | 0.171 | 130 | 133 | 0.981 | 0.00000908 | 960 |
| Loss of Function | 3.65 | 12 | 35.5 | 0.338 | 0.00000169 | 404 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.0017 | 0.0017 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.0013 | 0.0012 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has a ubiquitin-protein ligase activity acting as an E3 ubiquitin protein ligase or as an ubiquitin-ubiquitin ligase promoting elongation of ubiquitin chains on substrates. By mediating 'Lys-48'-linked polyubiquitination of proteins could target them for proteasomal degradation (PubMed:11435423). May also function as a chaperone, playing a role in transport to the cell membrane of BSG/Basigin for instance (PubMed:15946952). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357). {ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:15946952, ECO:0000269|PubMed:20676357}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- LoFtool
- 0.875
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 18.19
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |