PRF1 Gene (Perforin 1)
Key mediator of cytotoxic lymphocyte granule-dependent target cell death
Gene Information Card
| Symbol | PRF1 |
|---|---|
| Full Name | Perforin 1 (pore forming protein) |
| Gene Type | protein-coding |
| Chromosomal Location | 10q22.1 |
| NCBI Gene ID | 5551 ncbi.nlm.nih.gov/gene/5551 |
| Ensembl ID | ENSG00000180644 |
| UniProt ID | P14222 |
| OMIM ID | 170280 |
| HGNC ID | 9360 |
| Aliases | FLH2, HPLH2, P1, PFN1, PFP |
Description
PRF1 encodes perforin 1, a pore-forming protein stored in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Upon target cell recognition, perforin is released and, in the presence of calcium, polymerizes into transmembrane pores that facilitate the delivery of granzymes into the target cell, inducing apoptosis. Loss-of-function mutations in PRF1 cause familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a severe hyperinflammatory syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) | Biallelic loss-of-function mutations impair perforin-mediated cytotoxicity, leading to uncontrolled immune activation and cytokine storm. | OMIM #603553; ClinVar pathogenic variants |
| Hemophagocytic lymphohistiocytosis (HLH) | PRF1 mutations reduce NK/CTL lytic activity, contributing to HLH pathogenesis. | ClinVar; NCBI GeneReviews |
| Lymphoma (non-Hodgkin) | Partial perforin deficiency may impair immune surveillance; rare somatic mutations reported. | COSMIC; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | High |
| Lymph node | 10.2 | High |
| Bone marrow | 8.9 | Medium |
| Blood (whole) | 7.1 | Medium |
| Lung | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | 15.3 | High expression; functional perforin |
| YTS (NK cell line) | 14.8 | High expression |
| Jurkat (T cell line) | 0.5 | Low; not cytotoxic lineage |
| K562 (erythroleukemia) | 0.1 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.50delT (p.Leu17Argfs*34) | Frameshift | Common in FHL2 (allele frequency ~0.5% in some populations) | Loss of function; truncated protein |
| c.272C>T (p.Ala91Val) | Missense | Rare; reported in FHL2 | Loss of function; impaired pore formation |
| c.658G>A (p.Gly220Ser) | Missense | Rare; reported in FHL2 | Loss of function; reduced lytic activity |
| c.1122G>A (p.Trp374*) | Nonsense | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most PRF1 mutations are loss-of-function, leading to absent or defective perforin, impaired cytotoxicity, and FHL2.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Granzyme-mediated apoptotic pathway (Reactome: R-HSA-168256)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
• Perforin-dependent granzyme delivery (Reactome: R-HSA-168249)
Protein Summary
Perforin 1 is a 555-amino acid pore-forming protein (UniProt P14222) with a C2 domain for calcium-dependent membrane binding and a MACPF (membrane attack complex/perforin) domain for pore formation. It is synthesized as an inactive precursor, cleaved at the C-terminus during granule maturation. Active perforin oligomerizes into ~10 nm pores on target cell membranes, allowing granzyme entry and apoptosis. Defects cause FHL2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRF1 Knockout HEK293 Cell Line | EDJ-KQ50538 | Human | 5551 | Details Get a Quote |
| PRF1 Knockout HeLa Cell Line | EDJ-KQ54204 | Human | 5551 | Details Get a Quote |
| PRF1 Knockout A-549 Cell Line | EDJ-KQ62699 | Human | 5551 | Details Get a Quote |
| PRF1 Knockout HCT 116 Cell Line | EDJ-KQ71169 | Human | 5551 | Details Get a Quote |
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