# PSENEN

Source: https://onco.cc/targets/psenen/  
OnCo record `psenen` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

PSENEN (Gamma-secretase subunit PEN-2) is a gene. The public catalogues list it as a drug target, and an approved or late-stage drug is recorded against it. Tied to Desmoid tumour.

## Summary

Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyses 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 Notch and Wnt signalling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: presenilin enhancer, gamma-secretase subunit; Gamma-secretase subunit PEN-2; PEN2
- Tags: cancer-genes-wave
- Symbol: PSENEN
- Class: other
- Biology: Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyses 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 Notch and Wnt signalling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity. Besides its role in gamma-secretase complex, acts as a regulator of AMP-activated protein kinase (AMPK) activity in response to calorie restriction: binds metformin, an antidiabetic drug, promoting association with ATP6AP1, a subunit of the V-ATPase complex, leading to V-ATPase complex inhibition on lysosomes and AMPK activation via the AXIN1-STK11/LKB1 axis. Location: Endoplasmic reticulum membrane; Golgi apparatus, Golgi stack membrane; Cell membrane; Membrane (UniProt). Locus 19q13.12 (HGNC).
- Where found: Desmoid tumour: Open Targets association 0.50 with desmoid tumour (MONDO_0007608)

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.83. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:30100: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:30100
- UniProt Q9NZ42: https://www.uniprot.org/uniprotkb/Q9NZ42/entry
- NCBI Gene 55851: https://www.ncbi.nlm.nih.gov/gene/55851
- Ensembl ENSG00000205155: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000205155

## Connected records

- collections: [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/)

---
JSON: https://onco.cc/api/v1/entities/psenen.json