The following germline pathogenic missense variant of ATP2B3 ( NM_ NM_001001344.2) encoding the plasma membrane Ca2+ ATPase isoform 3 PMCA3 : c.1445G>A; p.G1107D in the calmodulin binding domain of the protein, has been found in two unrelated families.
Other mutations are: c.1445G>A; p.R482H, c. 2197G>A; p.G733R. The effect of the mutations were studied in vitro. All cause impairment of calcium homeostasis by defective calcium extrusion and/or by affecting the interplay with calmodulin and the autoinhibition process of the pump.
ATP2B3