PSENEN 2 Gene

The PSENEN gene (PSENEN stands for "Presenilin Enhancer, Gamma-Secretase Subunit") is a protein-coding gene located on chromosome 19q13.12. Alternative splicing leads to several transcript variants.

The encoded protein is an important subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid beta precursor protein). The gamma-secretase complex plays a role in the Notch and Wnt signaling cascades and in the regulation of downstream processes through its role in processing key regulatory proteins and by regulating cytosolic CTNNB1 levels. PSENEN modulates both the endoproteolysis of presenilin and gamma-secretase activity.

The PSENEN gene encodes a protein that is required for the Notch signaling pathway and for gamma-secretase activity and accumulation.

The gamma-secretase complex is composed of several subunits that cleave substrates within the transmembrane domain. This complex plays a role in the Notch and Wnt signaling cascades as well as in the regulation of downstream processes. It consists of four proteins

• presenilin
• nicastrin
• APH-1 and
• PEN2.

Presenilins, which are components of the gamma-secretase protein complex, are required for intramembrane processing of some type I transmembrane proteins, such as Notch proteins and beta-amyloid precursor protein. Signal transduction through Notch receptors mediates a wide range of cell developmental fates. Beta-amyloid precursor protein processing generates neurotoxic amyloid beta-peptides, the major component of senile plaques associated with Alzheimer's disease.

Diseases associated with PSENEN include:

Acne inversa, familial, 2, with or without Dowling-Degos disease (OMIM: 613736). This condition is a coexistence between hidradenitis suppurativa and Dowling-Degos disease (splice mutation c.62-1G>T/ Peter DCV et al.2020).

1. Pavlovsky M et al U(2018) A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN. Br J Dermatol 178:502-508.
2. Peter DCV et al.(2020) PSENEN mutation in coexistent hidradenitis suppurativa and Dowling-Degos disease. Indian Dermatol Online J 12:147-149.