ATP2C1 Gene

ATP2C1 (ATP2C1 is the acronym for "ATPase Secretory Pathway Ca2+ Transporting 1") is a protein coding gene located on chromosome 3q22.1. The enzyme encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent ATPase catalyzes the hydrolysis of ATP in conjunction with the transport of calcium ions. Mutations in this gene cause pemphigus chronicus benignus familiaris, also called Hailey-Hailey disease (Deng H et al. 2017), a localized autosomal dominant acantholytic disorder of the skin. Alternatively spliced transcript variants encoding different isoforms have been identified. An important paralog of this gene is ATP2C2.

The enzyme encoded by the ATP2C1 gene, an ATP-driven calcium pump supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for the processing and transport of newly synthesized proteins in the secretory pathway. Within a catalytic cycle, it takes up Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and releases them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is accompanied by transient phosphorylation, which shifts the conformation of the pump from an inward to an outward state. ATPase is responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, which contributes to keratinocyte differentiation and epidermal integrity. Furthermore, the enzyme is involved in the uptake of Ca(2+) and Mn(2+) ions into the Golgi store of hippocampal neurons and regulates protein trafficking required for neuronal polarity. It may also play a role in maintaining Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity.

1. Deng H et al (2017) The role of the ATP2C1 gene in Hailey-Hailey disease. Cell Mol Life Sci 74: 3687-3696.
2. Yang L et al (2021) Generalized Hailey-Hailey disease: Novel splice-site mutations of ATP2C1 gene in Chinese population and a literature review. Mol Genet Genomic Med 9: e1580.