PPIB
Basic information
Region (hg38): 15:64155740-64163134
Links
Phenotypes
GenCC
Source:
- 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:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Osteogenesis imperfecta, type IX | AR | General | 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 | Musculoskeletal | 19781681; 20089953; 22718341; 23613367 |
ClinVar
This is a list of variants' phenotypes submitted to
- 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 | 25 | 33 | ||||
missense | 38 | 42 | ||||
nonsense | 2 | |||||
start loss | 0 | |||||
frameshift | 4 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 5 | |||||
splice region | 1 | 1 | 2 | |||
non coding | 22 | 22 | 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) | ||
15-64155820-T-TA | Osteogenesis Imperfecta, Recessive | Benign (Aug 20, 2019) | ||
15-64155820-T-TAA | Osteogenesis Imperfecta, Recessive | Uncertain significance (Jun 14, 2016) | ||
15-64155833-A-C | Osteogenesis imperfecta type 9 | Uncertain significance (Jan 13, 2018) | ||
15-64155833-A-AC | Osteogenesis Imperfecta, Recessive | Uncertain significance (Jun 14, 2016) | ||
15-64155869-G-A | Osteogenesis imperfecta type 9 | Uncertain significance (Apr 06, 2018) | ||
15-64155943-G-A | Osteogenesis imperfecta type 9 | Uncertain significance (Jan 12, 2018) | ||
15-64155958-C-G | Osteogenesis imperfecta type 9 | Uncertain significance (Jan 13, 2018) | ||
15-64156002-A-T | Osteogenesis imperfecta type 9 | Benign (Jan 13, 2018) | ||
15-64156009-G-T | Osteogenesis imperfecta type 9 | Uncertain significance (Apr 27, 2017) | ||
15-64156011-T-C | Osteogenesis imperfecta type 9 | Uncertain significance (Jan 12, 2018) | ||
15-64156028-C-A | Uncertain significance (Oct 17, 2022) | |||
15-64156034-C-A | Osteogenesis imperfecta | Uncertain significance (Apr 06, 2022) | ||
15-64156048-T-C | Uncertain significance (Nov 03, 2023) | |||
15-64156050-C-T | PPIB-related disorder | Likely benign (Dec 15, 2023) | ||
15-64156058-C-T | Inborn genetic diseases | Uncertain significance (Apr 09, 2024) | ||
15-64156059-G-A | Osteogenesis imperfecta type 9 | Likely benign (Jan 11, 2019) | ||
15-64156068-G-A | Likely benign (Oct 15, 2023) | |||
15-64156072-T-C | Uncertain significance (Mar 28, 2017) | |||
15-64156077-G-A | Osteogenesis imperfecta type 9 | Conflicting classifications of pathogenicity (Dec 02, 2023) | ||
15-64156094-G-A | Likely benign (Oct 16, 2023) | |||
15-64156105-C-T | not specified • Osteogenesis imperfecta • Inborn genetic diseases | Conflicting classifications of pathogenicity (Mar 19, 2024) | ||
15-64156107-GCTGT-G | Osteogenesis imperfecta type 9 | Pathogenic (Nov 01, 2012) | ||
15-64156114-GTCTT-G | Osteogenesis imperfecta type 9 • Osteogenesis imperfecta | Pathogenic (Feb 16, 2023) | ||
15-64156126-T-G | Uncertain significance (Aug 22, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PPIB | protein_coding | protein_coding | ENST00000300026 | 5 | 7394 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.0000472 | 0.434 | 125722 | 0 | 26 | 125748 | 0.000103 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.299 | 119 | 129 | 0.926 | 0.00000768 | 1416 |
Missense in Polyphen | 43 | 53.453 | 0.80444 | 589 | ||
Synonymous | -1.12 | 63 | 52.6 | 1.20 | 0.00000343 | 428 |
Loss of Function | 0.332 | 7 | 8.01 | 0.874 | 3.46e-7 | 106 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000145 | 0.000145 |
Ashkenazi Jewish | 0.0000992 | 0.0000992 |
East Asian | 0.000109 | 0.000109 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000132 | 0.000132 |
Middle Eastern | 0.000109 | 0.000109 |
South Asian | 0.00 | 0.00 |
Other | 0.000489 | 0.000489 |
dbNSFP
Source:
- 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
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
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