The role of the ATP2C1 gene in Hailey–Hailey disease

Abstract

Hailey-Hailey disease (HHD) is a rare autosomal dominant acantholytic dermatosis, characterized by a chronic course of repeated and exacerbated skin lesions in friction regions. The pathogenic gene of HHD was reported to be the ATPase calcium-transporting type 2C member 1 gene (ATP2C1) located on chromosome 3q21-q24. Its function is to maintain normal intracellular concentrations of Ca/Mn by transporting Ca/Mn into the Golgi apparatus. ATP2C1 gene mutations are reportedly responsible for abnormal cytosolic Ca/Mn levels and the clinical manifestations of HHD. Environmental factors and genetic modifiers may also affect the clinical variability of HHD. This article aims to critically discuss the clinical and pathological features of HHD, differential diagnoses, and genetic and functional studies of the ATP2C1 gene in HHD. Further understanding the role of the ATP2C1 gene in the pathogenesis of HHD by genetic, molecular, and animal studies may contribute to a better clinical diagnosis and provide new strategies for the treatment and prevention of HHD.

A sex-stratified genome-wide association study of tuberculosis using a multi-ethnic genotyping array

“…The first interaction of interest is between RNF125 gene (rs35996537) and URI1 (rs1118924), involved in downregulation of CD 4+ /CD 38− T-cells and PBMCs in HIV-1 positive individuals and NF-kB/CSN2/Snail pathway, activated by TNFα respectively (60,61). Second the interaction between rs386560079 (ATP2C1), which is involved in regulation of intracellular Ca 2+ /Mn 2+ concentrations through the Golgi apparatus (62) and rs6498130 (CIITA). Variants in the CIITA gene reduce the expression of MHC class II proteins and receptors resulting in an immune privilege phenotype (63).…”

Dermoscopic and reflectance confocal microscopic presentation of Hailey‐Hailey disease: A case series

“…This gene encodes a Ca 2+ /Mn 2+ ATPase which is a calcium pump present on the Golgi apparatus. 3,4 Mutations will result in calcium deposition failure, ending in desmosomal separation, keratinocyte adhesion defects, and acantholysis. 5 Skin lesions usually develop in the second to fourth decades of life, with equal sex incidence.…”

Improvement of Hailey–Hailey disease with low‐dose naltrexone

“…HHD is caused by mutations in the ATP2C1 gene, encoding a calcium/manganese transporter protein found in the Golgi apparatus (secretory pathway Ca 2+ ‐ATPase isoform 1, SPCA1). Dysfunction of SPCA1 leads to defective calcium homeostasis and consequently loss of desmosomal adhesion between keratinocytes . As the role of the Golgi apparatus is largely in post‐translational protein modifications it is tempting to speculate that naltrexone, which has been reported to act as a molecular chaperone, may increase levels of functioning SPCA1 and thus counteract some ATP2C1 gene mutation effects .…”