GeneBe

PPIB

protein-coding

peptidylprolyl isomerase B, the group of Cyclophilin peptidylprolyl isomerases

Gene summary

The protein encoded by this gene is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta. [provided by RefSeq, Oct 2009]

MANE transcript

NM_000942.5

Inheritance

AD, AR

ClinVar variants

P:23U:72B:44

Top phenotype

Osteogenesis imperfecta, type IX

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr15:64,155,740-64,163,134

External References & Databases

Ensembl (ENSG00000166794)NCBI Gene (5479)OMIM (123841)HGNC:9255GenCCUniProt (P23284)AlphaFoldClinVar (PPIB)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteogenesis imperfecta type 4SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008148

Submitter: Orphanet

osteogenesis imperfecta type 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009805

Submitter: PanelApp Australia

osteogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008147

Submitter: Orphanet

osteogenesis imperfecta type 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009805

Submitter: Labcorp Genetics (formerly Invitae)

osteogenesis imperfecta type 9MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009805

Submitter: Ambry Genetics

osteogenesis imperfecta type 3SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009804

Submitter: Orphanet

Clinical Genomic Database (CGD)

Osteogenesis imperfecta, type IXAR

Manifestation: Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 19781681; 20089953; 22718341; 23613367Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPIB variants in ClinVar

8 Conditions Cataloged
not providedTotal: 119
Inborn genetic diseasesTotal: 34
Osteogenesis imperfecta type 9Total: 28
not specifiedTotal: 14
Osteogenesis imperfectaTotal: 12
PPIB-related disorderTotal: 7
EBV-positive nodal T- and NK-cell lymphomaTotal: 1
Osteogenesis imperfecta type IIITotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000942.5. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
40
clinvar
1
clinvar
 46
missense
1
clinvar
5
clinvar
57
clinvar
3
clinvar
 66
nonsense
2
clinvar
2
clinvar
 4
start loss
1
clinvar
 1
frameshift
5
clinvar
5
clinvar
1
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
7
clinvar
 11
Total91472431139

Highest pathogenic variant AF is 0.000010945574

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000942.5RefSeqNP_000933.15MANE Select
ENST00000300026.4EnsemblENSP00000300026.45MANE Select
ENST00000680158.1EnsemblENSP00000504873.14Standard
ENST00000681397.1EnsemblENSP00000506584.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Ibuprofen Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Ibuprofen Metabolism Pathway
  • Morphine Metabolism Pathway
  • Irinotecan Action Pathway

Biological Process

  • protein peptidyl-prolyl isomerization
  • positive regulation of multicellular organism growth
  • protein refolding
  • positive regulation by host of viral process
  • positive regulation by host of viral genome replication

Molecular Function

  • RNA binding
  • peptidyl-prolyl cis-trans isomerase activity
  • protein binding
  • collagen binding
  • cyclosporin A binding

Cellular Component

  • nucleus
  • endoplasmic reticulum
  • endoplasmic reticulum lumen
  • focal adhesion
  • membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000300026
Coding exons
5
Length
7394
Individuals with no LoFs
125722
Homozygous LoFs
0
Heterozygous LoFs
26
Defined
125748
p
0.000103
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2991191290.9260.000007681416
Missense (PolyPhen)4353.4530.80444589
Synonymous-1.126352.61.200.00000343428
Loss of Function0.33278.010.8743.46e-7106

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000140.00014rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000110.00011rare
Finnish00.0absent
European (Non-Finnish)0.000130.00013rare
South Asian00.0absent
Other0.000490.00049rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. {ECO:0000269|PubMed:20676357}.;
Disease
DISEASE: Osteogenesis imperfecta 9 (OI9) [MIM:259440]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI9 is a severe autosomal recessive form of the disorder. {ECO:0000269|PubMed:19781681, ECO:0000269|PubMed:20089953}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.400

Intolerance Scores

LoFtool
0.665
RVIS EVS
-0.34
RVIS percentile EVS
30.07

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.644

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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