Hailey-Hailey disease as an orthodisease of PMR1 deficiency inSaccharomyces cerevisiae

Abstract

The term orthodisease has recently been introduced to define human disorders in which the pathogenic gene has orthologs in model organism genomes. Here, we describe Hailey–Hailey disease (HHD), a blistering skin disorder caused by haploinsufficiency of ATP2C1 as an orthodisease from a Saccharomyces cerevisiae perspective. ATP2C1 encodes the human secretory pathway Ca2+/Mn2+ ATPase hSPCA1 and is orthologous to the PMR1 gene in S. cerevisiae. hSPCA1 fully complements PMR1 deficiency in yeast and pmr1ΔS. cerevisiae has proved to be a valuable tool to screen ATP2C1 mutations and address potential pathogenic/pharmacologic mechanisms in HHD. Consequently, this human skin disorder is an ideal example of an orthodisease