PSEN2 (Presenilin-2) variants and mutations

PSEN2 (also known as Presenilin-2) is a human protein-coding gene encoding a presenilin-2 protein. Its gamma-secretase activity contributes to intramembrane cleavage of APP and other substrates in endolysosomal and cellular membranes. Pathogenic variants are a rare cause of autosomal dominant Alzheimer disease, generally with more variable penetrance and age of onset than PSEN1 variants. This analysis covers 765 PSEN2 variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes early-onset autosomal dominant Alzheimer disease, desmoid tumor, and dilated cardiomyopathy 1V. Example PSEN2 variants include M1R, L2F, and L2V.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable PSEN2 variants

Examples include M1R, L2F, L2V, L2L, T3K, T3T, F4L, F4F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.