{"entity":{"id":"psenen","kind":"target","name":"PSENEN","aka":["presenilin enhancer, gamma-secretase subunit","Gamma-secretase subunit PEN-2","PEN2"],"tldr":"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.\n\n","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:30100","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:30100"},{"label":"UniProt Q9NZ42","url":"https://www.uniprot.org/uniprotkb/Q9NZ42/entry"},{"label":"NCBI Gene 55851","url":"https://www.ncbi.nlm.nih.gov/gene/55851"},{"label":"Ensembl ENSG00000205155","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000205155"}],"tags":["cancer-genes-wave"],"related":["open-targets"],"cancers":["desmoid-tumour"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PSENEN","role":["drug-target"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:30100","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:30100","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NZ42","url":"https://www.uniprot.org/uniprotkb/Q9NZ42/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000205155","url":"https://platform.opentargets.org/target/ENSG00000205155/associations","note":"per-cancer scores at or above 0.5: desmoid tumour 0.50 (GraphQL API, CC0)"}],"distribution":"one-type","specificityNote":"Specificity not established: no corpus medicine is aimed at it and the catalogues give it only the role drug-target; HPA finds the RNA tissue enhanced, which says where the protein sits but not whether the tumour differs from normal tissue. HPA PSENEN: RNA tissue enhanced (choroid plexus 320 nTPM); high antibody staining in 10 normal tissues; highest cancer staining melanoma (2 of 10 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST)); Open Targets associates it with 1 specific cancer type at or above 0.5 (desmoid tumor). (No rule of scripts/fetch-target-specificity.ts fired.)","specificitySources":[{"label":"Human Protein Atlas PSENEN tissue","url":"https://www.proteinatlas.org/ENSG00000205155-PSENEN/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000205155 associations","url":"https://platform.opentargets.org/target/ENSG00000205155/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:30100","ensembl":"ENSG00000205155","uniprot":"Q9NZ42","entrez":"55851","firstDescribed":1999,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Zhao et al, 1999, \"Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients\".","firstDescribedSource":"https://www.uniprot.org/uniprotkb/Q9NZ42/entry","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).","whereFound":["Desmoid tumour: Open Targets association 0.50 with desmoid tumour (MONDO_0007608)"],"targetClass":"other","prevalence":[]},"route":"/targets/psenen/","neighbours":{"collection":[{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","route":"/cancers/desmoid-tumour/"}]}}