PSENEN

presenilin enhancer, gamma-secretase subunit

2 disorders 2 causative 19q13.12 gene with protein product

HGNC:30100 Monarch NCBI Gene 55851 ENSG00000205155 UniProt Q9NZ42 OMIM 607632

Aliases: PEN2.

Normal function · from ai-gene-review (Q9NZ42, commit 79fe13b38970) · AI-generated, not KB evidence

PSENEN encodes PEN-2, a small multipass membrane protein and essential non-catalytic subunit of the gamma-secretase intramembrane protease complex. Together with a presenilin catalytic subunit, nicastrin, and APH1A or APH1B, PEN-2 promotes presenilin maturation/endoproteolysis, gamma-secretase complex stability and trafficking, and intramembrane cleavage of substrates including APP and Notch receptors. PEN-2 localizes primarily to endoplasmic-reticulum and cis-Golgi membranes, with evidence for cell-membrane and other membrane compartments; additional orthology-based evidence links PEN-2 to energy-stress signaling through V-ATPase/AMPK/TORC1 regulation.

PSENEN/PEN-2 is an essential non-catalytic gamma-secretase subunit that promotes presenilin endoproteolysis, stabilizes and traffics the assembled complex, and enables presenilin-dependent intramembrane cleavage of APP, Notch receptors, and related membrane substrates.

molecular function: endopeptidase activator activity · contributes to molecular function: aspartic endopeptidase activity, intramembrane cleaving · directly involved in: membrane protein intracellular domain proteolysis; Notch receptor processing; amyloid precursor protein catabolic process; amyloid-beta formation; protein processing; positive regulation of endopeptidase activity · locations: endoplasmic reticulum membrane; Golgi cisterna membrane; Golgi membrane; plasma membrane; endosome membrane; membrane · in complex: gamma-secretase complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Dowling-Degos Disease	causative	mechanism: Notch Pathway Glycosylation and Cleavage Deficiency subtype: PSENEN-related DDD scoped to subtype: PSENEN-related DDD
Hidradenitis Suppurativa	causative	mechanism: Gamma-Secretase Loss of Function subtype: AI2 scoped to subtype: AI2

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.