In the case of CF, the main cause of disease (approximately 90% of cases) is the deletion of F508 from NBD1 of CFTR.17 The deletion of I507, the adjacent residue, also results in disease.45 We find that deletion of these residues from the F508 loop substructure leads to non-native dynamic coupling interactions within NBD1. This evidence concerns the gene CFTR and cystic fibrosis.