In-silico characterization of PSEN1 missense variants associated with acne inversa

Acne inversa, or hidradenitis suppurativa, is a chronic inflammatory skin disorder that causes painful and reoccurring abscesses. The PSEN1 gene is responsible for the sequence coding for the presenilin 1 protein, which is part of the gamma-secretase complex and is responsible for cleaving multiple peptides. Acne inversa occurs when the Notch signaling pathway of PSEN1 is disrupted. Analysis of multiple pathogenicity predictors and simulated aqueous environments of the transmembrane protein in its native state and mutated state through molecular dynamics simulation predicted deleterious effects from swap of tyrosine to cysteine at the highly conserved and buried position 189.