PPIB

peptidylprolyl isomerase B, the group of Cyclophilin peptidylprolyl isomerases

Basic information

Region (hg38): 15:64155740-64163134

Links

ENSG00000166794 ∙ NCBI:5479 ∙ OMIM:123841 ∙ HGNC:9255 ∙ Uniprot:P23284 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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
• osteogenesis imperfecta type 9 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 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	25	3	33
missense		2	38	2		42
nonsense	1		1			2
start loss						0
frameshift	1	3				4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			1	1		2
non coding			22	22	6	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: gnomAD

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: 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

	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