PPIB

peptidylprolyl isomerase B, the group of Cyclophilin peptidylprolyl isomerases

Basic information

Region (hg38): 15:64155740-64163134

Links

ENSG00000166794NCBI:5479OMIM:123841HGNC:9255Uniprot:P23284AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • osteogenesis imperfecta type 9 (Strong), mode of inheritance: AR
  • osteogenesis imperfecta type 2 (Supportive), mode of inheritance: AD
  • osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
  • osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Osteogenesis imperfecta, type IXARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal19781681; 20089953; 22718341; 23613367

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPIB gene.

  • not provided (3 variants)
  • Osteogenesis imperfecta type 9 (2 variants)
  • Osteogenesis imperfecta (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPIB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
5
clinvar
25
clinvar
3
clinvar
33
missense
2
clinvar
38
clinvar
2
clinvar
42
nonsense
1
clinvar
1
clinvar
2
start loss
0
frameshift
1
clinvar
3
clinvar
4
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
1
clinvar
5
splice region
1
1
2
non coding
22
clinvar
22
clinvar
6
clinvar
50
Total 3 8 68 49 9

Highest pathogenic variant AF is 0.0000197

Variants in PPIB

This is a list of pathogenic ClinVar variants found in the PPIB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
15-64155818-A-AT Osteogenesis Imperfecta, Recessive Benign/Likely benign (Aug 11, 2019)316695
15-64155820-T-TA Osteogenesis Imperfecta, Recessive Benign (Aug 20, 2019)316696
15-64155820-T-TAA Osteogenesis Imperfecta, Recessive Uncertain significance (Jun 14, 2016)316697
15-64155833-A-C Osteogenesis imperfecta type 9 Uncertain significance (Jan 13, 2018)316699
15-64155833-A-AC Osteogenesis Imperfecta, Recessive Uncertain significance (Jun 14, 2016)316698
15-64155869-G-A Osteogenesis imperfecta type 9 Uncertain significance (Apr 06, 2018)885311
15-64155943-G-A Osteogenesis imperfecta type 9 Uncertain significance (Jan 12, 2018)885312
15-64155958-C-G Osteogenesis imperfecta type 9 Uncertain significance (Jan 13, 2018)885313
15-64156002-A-T Osteogenesis imperfecta type 9 Benign (Jan 13, 2018)886214
15-64156009-G-T Osteogenesis imperfecta type 9 Uncertain significance (Apr 27, 2017)886215
15-64156011-T-C Osteogenesis imperfecta type 9 Uncertain significance (Jan 12, 2018)316700
15-64156028-C-A Uncertain significance (Oct 17, 2022)1505005
15-64156034-C-A Osteogenesis imperfecta Uncertain significance (Apr 06, 2022)1702049
15-64156048-T-C Uncertain significance (Nov 03, 2023)2921248
15-64156050-C-T PPIB-related disorder Likely benign (Dec 15, 2023)2185123
15-64156058-C-T Inborn genetic diseases Uncertain significance (Apr 09, 2024)3309168
15-64156059-G-A Osteogenesis imperfecta type 9 Likely benign (Jan 11, 2019)811804
15-64156068-G-A Likely benign (Oct 15, 2023)757737
15-64156072-T-C Uncertain significance (Mar 28, 2017)426916
15-64156077-G-A Osteogenesis imperfecta type 9 Conflicting classifications of pathogenicity (Dec 02, 2023)316701
15-64156094-G-A Likely benign (Oct 16, 2023)2921230
15-64156105-C-T not specified • Osteogenesis imperfecta • Inborn genetic diseases Conflicting classifications of pathogenicity (Mar 19, 2024)218476
15-64156107-GCTGT-G Osteogenesis imperfecta type 9 Pathogenic (Nov 01, 2012)41422
15-64156114-GTCTT-G Osteogenesis imperfecta type 9 • Osteogenesis imperfecta Pathogenic (Feb 16, 2023)16925
15-64156126-T-G Uncertain significance (Aug 22, 2022)1376786

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PPIBprotein_codingprotein_codingENST00000300026 57394
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.00004720.4341257220261257480.000103
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2991191290.9260.000007681416
Missense in Polyphen4353.4530.80444589
Synonymous-1.126352.61.200.00000343428
Loss of Function0.33278.010.8743.46e-7106

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001450.000145
Ashkenazi Jewish0.00009920.0000992
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.0001320.000132
Middle Eastern0.0001090.000109
South Asian0.000.00
Other0.0004890.000489

dbNSFP

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.;
Pathway
Ibuprofen Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Ibuprofen Metabolism Pathway;Morphine Metabolism Pathway;Irinotecan Action Pathway;Morphine Action Pathway;Etoposide Action Pathway;Sorafenib Metabolism Pathway;Acetaminophen Metabolism Pathway;Vitamin A Deficiency;Irinotecan Metabolism Pathway;Etoposide Metabolism Pathway;Retinol Metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Prolactin Signaling Pathway;Prolactin;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Syndecan-1-mediated signaling events (Consensus)

Recessive Scores

pRec
0.400

Intolerance Scores

loftool
0.665
rvis_EVS
-0.34
rvis_percentile_EVS
30.07

Haploinsufficiency Scores

pHI
0.371
hipred
Y
hipred_score
0.815
ghis
0.600

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.644

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Ppib
Phenotype
limbs/digits/tail phenotype; skeleton phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

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;protein stabilization;bone development;chaperone-mediated protein folding;regulation of post-translational protein modification
Cellular component
nucleus;endoplasmic reticulum;endoplasmic reticulum lumen;focal adhesion;membrane;protein-containing complex;melanosome;perinuclear region of cytoplasm;extracellular exosome
Molecular function
RNA binding;peptidyl-prolyl cis-trans isomerase activity;protein binding;collagen binding;cyclosporin A binding;unfolded protein binding;RNA polymerase binding