1.A.17.1.21
Ano5 (GDD1, TMEM16E), of 913 aas and 10 TMSs, is an intracellular calcium-activated chloride channel in the endoplasmic reticulum. It positively modulates bone homeostasis via calcium signaling in GDD (Li et al. 2022), and is associated with bone fragility, limb girdle muscular dystrophy type 2L (LGMD2L), Miyoshi myopathy type 3 (MMD3), and gnathodiaphyseal dysplasia 1 (GDD1) in humans (Jin et al. 2017), but an Ano5 knock-out mutant in mice was not reported to exhibit such symptoms (Xu et al. 2015). The orthologue in mice is TC# 1.A.17.1.2.  TMEM16E may function as a phospholipid scramblase in intracellular membranes, promoting sperm motility and function (Gyobu et al. 2016).  Dysregulated calcium homeostasis prevents plasma membrane repair in Anoctamin 5/TMEM16E-deficient patient muscle cells (Chandra et al. 2019). Ano5 is involved in familial florid osseous dysplasia (Lv et al. 2019). Pharmacological inhibition of ANO5 or lack of ANO5, prevent Ca²⁺ uptake into the ER following plasma membrane damage and Ca²⁺ overload (Chandra et al. 2021). Thus, Cl^- uptake into the ER is required to sequester injury-promoted cytosolic Ca²⁺. Anoctamin 5 regulates the cell cycle and affects the prognosis in gastric cancer (Fukami et al. 2022). Thus, ANO5 may be a key mediator in tumor progression and promises to be a prognostic biomarker for gastric cancer. TMEM16E regulates endothelial cell procoagulant activity and thrombosis (Schmaier et al. 2023).