Protein / target

Perforin-1

Encoded byPRF1P14222Homo sapiensSwiss-Prot

UniProt: P14222 Ensembl: ENSG00000180644 HGNC: HGNC:9360 NCBI Gene: 5551

Small-molecule tractable

Druggability

High-Quality Ligand

Research papers

Protein at a glance

Biological role

Wide pore channel

Strongest disease association

Lymphohistiocytosis, Hemophagocytic

Via encoding gene PRF1 · Genetic evidence · score 0.92

Research activity

Emerging research

3 papers · latest 2024

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

Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells.

View complete UniProt function annotation

Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, PubMed:9058810, PubMed:9164947). Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease (PubMed:9058810). Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores (PubMed:20889983, PubMed:21037563). Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes (PubMed:20038786, PubMed:20225066, PubMed:24558045, PubMed:32299851). Facilitates the delivery of cationic cargo protein, while anionic or neural proteins are not delivered efficiently (PubMed:24558045). Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu (By similarity)

Subcellular location

Cytolytic granuleSecretedCell membraneEndosome lumen

Domains and Gene Ontology detail (28)

Domains & features

MACPFEGF-likeC2

Gene Ontology

Ccytolytic granule
Ccytolytic granule lumen
Cendosome lumen
Cextracellular region
Cimmunological synapse
Cmembrane
Cplasma membrane
Fcalcium ion binding
Fidentical protein binding
Fpore-forming activity
Fwide pore channel activity
Papoptotic process

555 aa · 61 kDa

Biological roles

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

Apoptosis & cell deathUniProt · GOImmune signallingGO

View supporting evidence

Apoptosis & cell death

·Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, a…
·apoptotic process
·granzyme-mediated programmed cell death signaling pathway

Immune signalling

·immune response to tumor cell
·T cell mediated cytotoxicity

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 PRF1

Gene-level evidence surfaced through the gene PRF1that 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.

Lymphohistiocytosis, Hemophagocytic

0.94Well supported

Genetic evidence dominant · Open Targets 0.83

Anemia, Aplastic

0.92Well supported

Genetic evidence dominant · Open Targets 0.65

Lymphoma, Non-Hodgkin's

0.92Well supported

Genetic evidence dominant · Open Targets 0.56

Genetic Diseases, Inborn

0.85Well supported

Genetic evidence dominant · Open Targets 0.52

Leukemia, Lymphoid

0.84Well supported

Genetic evidence dominant · Open Targets 0.51

View evidence synthesis (5)

Lymphohistiocytosis, HemophagocyticWell supported

0.94

agreement 0.82–1.00

Genetic78%Animal model20%Literature2%Genetic literaturedup

Open Targets aggregate 0.83 · 3 independent evidence families · 1 not counted as duplicate

Anemia, AplasticWell supported

0.92

agreement 0.78–1.00

Genetic98%Literature2%Genetic literaturedup

Open Targets aggregate 0.65 · 2 independent evidence families · 1 not counted as duplicate

Lymphoma, Non-Hodgkin'sWell supported

0.92

agreement 0.79–1.00

Genetic87%Animal model13%

Open Targets aggregate 0.56 · 2 independent evidence families

Genetic Diseases, InbornWell supported

0.85

agreement 0.71–0.99

Genetic99%Literature1%

Open Targets aggregate 0.52 · 2 independent evidence families

Leukemia, LymphoidWell supported

0.84

agreement 0.72–0.96

Genetic100%

Open Targets aggregate 0.51 · 1 independent evidence family

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

Lymphohistiocytosis, Hemophagocytic0.83

Anemia, Aplastic0.65

Lymphoma, Non-Hodgkin's0.56

Lymphoid neoplasm0.52

Genetic Diseases, Inborn0.52

Leukemia, Lymphoid0.51

Lymphoma0.48

Cutaneous melanoma0.37

Tractability

Small molecules — Emerging

Feasibility evidence (high-quality ligand and druggable family) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)

SM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.