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Protein / target

Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Encoded byPPIFP30405Homo sapiensSwiss-Prot
UniProt: P30405Ensembl: ENSG00000108179HGNC: HGNC:9259NCBI Gene: 10105
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Peptidyl-prolyl cis-trans isomerase

Strongest disease association

Hair color

Via encoding gene PPIF · Genetic evidence · score 0.26

Research activity

Emerging research

1 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.

View complete UniProt function annotation

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) (PubMed:26387735). 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 (PubMed:26387735). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (By similarity). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691)

Subcellular location

Mitochondrion matrix
Domains and Gene Ontology detail (22)

Domains & features

PPIase cyclophilin-type

Gene Ontology

  • Ccytoplasm
  • Cmembrane
  • Cmitochondrial matrix
  • Cmitochondrial permeability transition pore complex
  • Cmitochondrion
  • Fcyclosporin A binding
  • Fenzyme inhibitor activity
  • Fpeptidyl-prolyl cis-trans isomerase activity
  • Papoptotic process
  • Pcellular response to arsenic-containing substance
  • Pcellular response to calcium ion
  • Pcellular response to hydrogen peroxide

207 aa · 22 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Apoptosis & cell deathGO
View supporting evidence

Apoptosis & cell death

  • ·apoptotic process
  • ·mitochondrial outer membrane permeabilization involved in programmed cell death
  • ·negative regulation of apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PPIF

Gene-level evidence surfaced through the gene PPIF that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neurodegenerative Diseases
0.33Preliminary

Pathway evidence dominant · Open Targets 0.50 · no direct causal or clinical evidence

Diabetes Mellitus
0.28Limited support

Genetic evidence dominant · Open Targets 0.14

Hair color
0.26Limited support

Genetic evidence dominant · Open Targets 0.16

Diabetes Mellitus, Type 2
0.25Limited support

Genetic evidence dominant · Open Targets 0.15

Psoriasis
0.21Preliminary

Genetic evidence dominant · Open Targets 0.11

View evidence synthesis (5)
Neurodegenerative DiseasesPreliminary
0.33
agreement 0.16–0.51
Pathway98%Literature2%

Open Targets aggregate 0.50 · 2 independent evidence families · no direct causal or clinical evidence

Diabetes MellitusLimited support
0.28
agreement 0.14–0.42
Genetic67%Literature34%

Open Targets aggregate 0.14 · 2 independent evidence families

Hair colorLimited support
0.26
agreement 0.14–0.38
Genetic100%

Open Targets aggregate 0.16 · 1 independent evidence family

Diabetes Mellitus, Type 2Limited support
0.25
agreement 0.11–0.39
Genetic92%Literature8%

Open Targets aggregate 0.15 · 2 independent evidence families

PsoriasisPreliminary
0.21
agreement 0.09–0.34
Genetic76%RNA expression14%Literature11%

Open Targets aggregate 0.11 · 3 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neurodegenerative Diseases0.50
Hair color0.16
Diabetes Mellitus, Type 20.15
Diabetes Mellitus0.14
Metabolic Diseases0.11
Hyperlipidemias0.11
Psoriasis0.11

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (4)
SM · Structure with LigandPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Cyclophilin D in Mitochondrial Dysfunction: A Key Player in Neurodegeneration?11 cites

Coluccino G · Biomolecules · 2023

Recent

Cyclophilin D in Mitochondrial Dysfunction: A Key Player in Neurodegeneration?

Coluccino G · Biomolecules · 2023

Europe PMC papers linked directly to this protein.