PSENEN

Chr 19q13.12

presenilin enhancer, gamma-secretase subunit

Aliases:: PEN2
MANE:: ENST00000587708.7

OMIM: 607632 ↗NCBI: 55851 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

PSENEN · Q9NZ42

v62025-08-01

Predicted Aligned Error matrix for PSENEN — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

92.6/ 100

Very high

101 residues

Confidence breakdown

Very high(≥ 90)85%
Confident(70–90)13%
Low(50–70)2%
Very low(< 50)0%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial hidradenitis suppurativa
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pigmentary skin disorders
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Disease associations (Open Targets)

hidradenitis suppurativa
0.58
neurodegenerative disease
0.53
desmoid tumor
0.50
Dowling-Degos disease
0.46
Alzheimer disease
0.38
neoplasm
0.37
fibromatosis
0.28
Parkinson disease
0.26
mathematical ability
0.16
breast cancer
0.11

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Gamma-secretase subunit PEN-2

Essential 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) (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111). 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 (By similarity)