The PSENEN gene provides instructions for making a protein called presenilin enhancer 2 or PEN-2. This protein is one part (subunit) of a complex called gamma- (γ-) secretase. PEN-2 processes another subunit of the complex, presenilin 1, which is produced from the PSEN1 gene. This step is necessary for the γ-secretase complex to be functional.
The γ-secretase complex is located in the membrane that surrounds cells, where it cuts apart (cleaves) many different proteins that span the cell membrane (transmembrane proteins). This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function.
Health Conditions Related to Genetic Changes
At least three mutations in the PSENEN gene have been found to cause hidradenitis suppurativa, a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin that develop in hair follicles. The nodules tend to become inflamed and painful, and they produce significant scarring as they heal.
PSENEN gene mutations reduce the amount of functional PEN-2 produced in cells, so less of this protein is available to act as part of the γ-secretase complex. The resulting shortage of normal γ-secretase impairs cell signaling pathways, including Notch signaling. Although little is known about the mechanism, studies suggest that abnormal Notch signaling may promote the development of recurrent nodules in hair follicles and trigger inflammation in the skin.More About This Health Condition
MedlinePlus Genetics provides information about Dowling-Degos diseaseMore About This Health Condition
Other Names for This Gene
- gamma-secretase subunit PEN-2
- hematopoietic stem/progenitor cells protein MDS033
- presenilin enhancer 2 homolog
- presenilin enhancer gamma secretase subunit
- presenilin enhancer gamma-secretase subunit
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Melnik BC, Plewig G. Impaired Notch signalling: the unifying mechanism explaining the pathogenesis of hidradenitis suppurativa (acne inversa). Br J Dermatol. 2013 Apr;168(4):876-8. doi: 10.1111/bjd.12068. Epub 2013 Jan 31. Citation on PubMed
- Pink AE, Simpson MA, Brice GW, Smith CH, Desai N, Mortimer PS, Barker JN, Trembath RC. PSENEN and NCSTN mutations in familial hidradenitis suppurativa (Acne Inversa). J Invest Dermatol. 2011 Jul;131(7):1568-70. doi: 10.1038/jid.2011.42. Epub 2011 Mar 17. Citation on PubMed
- Pink AE, Simpson MA, Desai N, Dafou D, Hills A, Mortimer P, Smith CH, Trembath RC, Barker JNW. Mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 underlie rare forms of hidradenitis suppurativa (acne inversa). J Invest Dermatol. 2012 Oct;132(10):2459-2461. doi: 10.1038/jid.2012.162. Epub 2012 May 24. Citation on PubMed
- Pink AE, Simpson MA, Desai N, Trembath RC, Barker JNW. γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis. J Invest Dermatol. 2013 Mar;133(3):601-607. doi: 10.1038/jid.2012.372. Epub 2012 Oct 25. Review. Citation on PubMed
- Prokop S, Haass C, Steiner H. Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments. J Neurochem. 2005 Jul;94(1):57-62. Citation on PubMed
- Wang B, Yang W, Wen W, Sun J, Su B, Liu B, Ma D, Lv D, Wen Y, Qu T, Chen M, Sun M, Shen Y, Zhang X. Gamma-secretase gene mutations in familial acne inversa. Science. 2010 Nov 19;330(6007):1065. doi: 10.1126/science.1196284. Epub 2010 Oct 7. Citation on PubMed