PRF1 Gene

The PRF1 gene (PRF1 stands for "perforin") is a protein-coding gene located on chromosome 10q22.1. Related signaling pathways include apoptosis-induced DNA fragmentation and IL12 signaling through STAT4.

The PRF1 gene encodes a pore-forming protein (perforin) with structural similarities to complement component C9. Perforin plays a key role in secretory granule-dependent cell death and defense against virus-infected or neoplastic cells. Perforin plays an important role in killing other cells that are recognized as foreign by the immune system, e.g., in transplant rejection or in some forms of autoimmune diseases.

In its calcium-bound form, perforin can penetrate the membrane of target cells, where it oligomerizes and forms large pores. It promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes via pore formation, which enter the cell and subsequently induce cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane within target cells has not yet been determined.

Mutations in this gene have been associated with a variety of human diseases, including diabetes, multiple sclerosis, lymphoma, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia. Assured is the association of the PRF1 gene with:

• Familial Hemophagocytic Lymphohistiocytosis Type 2 (OMIM: 267700).

1. Arico M et al (2002) Haemophagocytic lymphohistiocytosis: proposal of a diagnostic algorithm based on perforin expression. Brit J Haemat 119: 180-188.
2. Chiapparini L et al (2011) Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss (sic) diagnosis. Neurol Sci 32: 473-477.
3. Clementi R et al (2002) Adult onset and atypical presentation of hemophagocytic lymphohistiocytosis in siblings carrying PRF1 mutations. (Letter) Blood 100: 2266-2267.
4. Janka GE et al (2004) Modern management of children with haemophagocytic lymphohistiocytosis. Brit J Haemat 124: 4-14.
5. Kletzel M et al (1986) Chromosome abnormalities in familial hemophagocytic lymphohistiocytosis. Cancer 57: 2153-2157.