PSEN1 (Presenilin-1) variants and mutations

PSEN1 (also known as Presenilin-1) is a human protein-coding gene encoding a presenilin-1 protein. Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease. This analysis covers 848 PSEN1 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes Alzheimer disease 3, acne inversa, familial, 3, and Pick disease. Example PSEN1 variants include M1?, E3K, and E3Q.

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 PSEN1 variants

Examples include M1?, E3K, E3Q, E3E, L4Y, P5L, P5S, P5T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.