PSENEN Gene

The PSENEN gene (PSENEN is the acronym for Presenilin Enhancer, Gamma-Secretase Subunit) is a protein-coding gene located on chromosome 19q13.12. PSENEN encodes PEN2 a protein required for the activity and accumulation of the gamma-secretase complex, an endoprotease.

PEN2 represents an essential subunit of the gamma-secretase complex, an internal protease that catalyzes intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). The gamma-secretase complex is composed of several subunits that cleaves substrates within the transmembrane domain. This complex plays a role in the Notch and Wnt signaling cascades and in the regulation of downstream processes. It consists of four proteins

• Presenilin
• Nicastrin
• APH-1 and
• PEN2.

PEN2 modulates both endoproteolysis of presenilin and gamma-secretase activity. Mutations leading to haploinsufficiency of the gene are associated with familial hidradenitis suppurativa (acne inversa-2 - ACNINV2) with or without Dowling-Degos disease (OMIM: 613736). Alternative splicing results in multiple transcript variants.

1. Nomura T (2020) Hidradenitis Suppurativa as a Potential Subtype of Autoinflammatory Keratinization Disease. Front Immunol11:847.
2. Zhou P et al (2021) Mutations in γ-secretase subunit-encoding PSENEN gene alone may not be sufficient for the development of acne inversa. J Dermatol Sci 103:73-81.