Table 1.

Classes of CFTR mutations and molecular mechanisms.

Class	Molecular Mechanism	Mutation Examples
1	Non-sense mutation: premature stop codon → defective protein synthesis (no CFTR expression)	R553X, G542X [84]
2	Missense mutation: either (1) Misfolded CFTR protein and, or (2) not transported to the destination (or if so, only in residual amounts)	F508del (Most prevalent), N1303K [69,72]
3	Missense mutation (AA substitution): reduced of lack of CFTR opening in response to agonists → gating defect	G551D (Ivacaftor corrects), G1244E [69,74]
4	Missense mutation (AA substitution): restrict Cl− transport across the channel → conductance defect	R117H, R334W [85,86]
5	Splicing defect: improper processing of CFTR mRNA → less CFTR protein abundance on the cell surface but the proteins are normal	A455E (Least prevalent) [81]
6	CFTR is functional, but unstable due to rapid removal and degradation	N287Y [87]

mRNA: messenger RNA.