Table 1 Depicting various classes of mutations, the primary defect and the outcome with examples
From: Cystic fibrosis: current therapeutic targets and future approaches
Mutation class | Defect | Outcome | Common mutations |
|---|---|---|---|
I | Protein production | Complete absence of CFTR protein due to premature mRNA termination (nonsense or frame shift mutation) [18, 21, 22] | G542X, W1282X, R553X, 621+G>T |
II | Protein processing | Inability of protein to localize to correct cellular location due to abnormal post-translational modifications [18] | F508del, N1303K, A455E |
III | Protein regulation | Decreased activity of protein (chloride channel) in response to ATP due to abnormalities of the nuclear binding fold regions [18] | G551D |
IV | Protein conduction | Frequency of flow of ions and channel opening duration are reduced though there is generation of chloride currents on stimulation with cAMP [18] | R117H |
V | Reduced amount of functional CFTR | Stability of mRNA and/or mature protein is compromised [19, 20] | A455E |
VI | Normal amount of functional CFTR | Enhanced turnover due to C-terminus abnormalities | Q1412X |