Hailey-Halley disease as an orthodisease of PMR1 deficiency in Saccharomyees cerevisiae

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 cererisiae perspective. ATP2C1 encodes the human secretory pathway Ca2+/Mn2+ ATPase hSPCA1 and is orthologous to the PiWR1 gene in S. cerevisiae. hSPCA1 fully complements PMR1 deficiency in yeast and pmr1 Delta S. 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. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.