This repositioning is critical for hormone-dependent activation of ANF-RGC; deletion of the WTAPELL motif results in an ANF-RGC that is unresponsive to ANF and ATP in the recombinant system (Duda et al., 2009) and in a genetically modified mouse model, causes hypertension and cardiac hypertrophy (Duda et al., 2013). This evidence concerns the gene NPPA and hypertensive disorder.