1.A.17.1.20
Anoctamin 3, ANO3 or TMEM16C or KCNT1/Slack, of 981 aas and 9 putative TMSs.  Has calcium-dependent phospholipid scramblase activity, scrambling phosphatidylcholine and galactosylceramide. Seems to act as a potassium channel regulator and may inhibit pain signaling; can facilitate KCNT1/Slack channel activity by promoting its full single-channel conductance at very low sodium concentrations and by increasing its sodium sensitivity (Scudieri et al. 2012). Mutations cause  (i) epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), (ii) autosomal dominant nocturnal frontal lobe epilepsy, and (iii) other types of early onset epileptic encephalopathies (EOEEs) (Ohba et al. 2015). TMEM16C/Slack regulation of excitatory synaptic plasticity via GluA1-containing AMPA Receptors is critical for the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats (Li et al. 2021). Specific mutational variants in TMS of ANO3 can be responsible for childhood-onset movement disorders with intellectual disability (Aihara et al. 2022).  ANO3 variants have been identified as the cause of craniocervical dystonia (Ousingsawat et al. 2024).  ANO3 variants may dysregulate intracellular Ca²⁺ signalling, as variants in other Ca²⁺ regulating proteins like hippocalcin (TC# 8.A.82.2.8) were also identified as causes of dystonia.  ANO3 is a Ca²⁺-activated phospholipid scramblase that also conducts ions. Impaired Ca²⁺ signalling and compromised activation of Ca²⁺-dependent K⁺ channels were detected in cells expressing ANO3 variants. The association between ANO3 variants and paroxysmal dystonia, represents a link between these variants and this specific dystonic phenotype (Ousingsawat et al. 2024).