Currently, twenty different germline missense mutations have been reported. No genotype-phenotype correlations emerged from analysis of variant positions in a linear protein model.
The effect of some of these mutations were studied in vitro in HEK cells transfected with ouabain-insensitive ATP1A1 constructs: cell viability appeared decreased in mutants after treatment with the ATPase inhibitor ouabain, thus demonstrating loss of ATPase function and suggesting haploinsufficiency as possible pathophysiologic mechanism.
ATP1A1