PPIF

peptidylprolyl isomerase F, the group of Cyclophilin peptidylprolyl isomerases

Basic information

Region (hg38): 10:79347468-79355334

Links

ENSG00000108179 ∙ NCBI:10105 ∙ OMIM:604486 ∙ HGNC:9259 ∙ Uniprot:P30405 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (9 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPIF 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					2	2
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	0	2

Variants in PPIF

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

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

Position	Type	Phenotype	Significance	ClinVar
10-79347601-G-C		not specified	Uncertain significance (Nov 30, 2022)
10-79347730-G-T		not specified	Uncertain significance (Jan 08, 2024)
10-79349091-G-A		not specified	Uncertain significance (May 25, 2022)
10-79349703-G-A		not specified	Uncertain significance (Nov 09, 2023)
10-79349716-C-T		not specified	Uncertain significance (Apr 13, 2023)
10-79351493-G-A		not specified	Uncertain significance (Mar 01, 2024)
10-79351499-A-G		not specified	Uncertain significance (May 27, 2022)
10-79351541-C-T		not specified	Uncertain significance (Jan 23, 2024)
10-79351574-G-A		not specified	Uncertain significance (Mar 29, 2022)
10-79352358-T-G		not specified	Uncertain significance (Mar 24, 2023)
10-79352382-A-G		not specified	Uncertain significance (Oct 26, 2022)
10-79352385-A-C		not specified	Uncertain significance (Feb 27, 2024)
10-79353738-G-A		not specified	Uncertain significance (Jun 06, 2023)
10-79353756-G-T		not specified	Uncertain significance (Feb 14, 2023)
10-79353779-C-T			Benign (Jun 18, 2018)
10-79353830-C-G			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPIF	protein_coding	protein_coding	ENST00000225174	6	7869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00199	0.753	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	88	108	0.817	0.00000610	1335
Missense in Polyphen		47	53.915	0.87174		599
Synonymous	0.916	38	45.9	0.828	0.00000305	420
Loss of Function	0.909	5	7.73	0.647	3.27e-7	98

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000490	0.000489
South Asian	0.00121	0.00121
Other	0.00	0.00

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 (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis. {ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735}.
• Pathway: Huntington,s disease - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);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 (Consensus)

Recessive Scores

• pRec: 0.199

Haploinsufficiency Scores

• pHI: 0.245
• hipred: N
• hipred_score: 0.394
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ppif
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;response to ischemia;protein folding;regulation of proton-transporting ATPase activity, rotational mechanism;negative regulation of ATPase activity;protein refolding;negative regulation of apoptotic process;regulation of mitochondrial membrane permeability;cellular response to hydrogen peroxide;cellular response to arsenic-containing substance;cellular response to calcium ion;positive regulation of release of cytochrome c from mitochondria;negative regulation of release of cytochrome c from mitochondria;negative regulation of oxidative phosphorylation;regulation of mitochondrial membrane permeability involved in programmed necrotic cell death;mitochondrial outer membrane permeabilization involved in programmed cell death;negative regulation of oxidative phosphorylation uncoupler activity;negative regulation of intrinsic apoptotic signaling pathway
• Cellular component: mitochondrion;mitochondrial proton-transporting ATP synthase complex;mitochondrial permeability transition pore complex;membrane
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;protein binding;cyclosporin A binding;unfolded protein binding