CYSTIC FIBROSIS (r)F 508/CFTRF508

F508 (ΔF508 or F508del) is the most common CFTR gene mutation in cystic fibrosis: a deletion of the amino acid phenylalanine at position 508. It causes misfolding and degradation of CFTR, preventing functional chloride channels from reaching the cell surface, which leads to impaired salt and water transport, thick mucus, recurrent lung infections, and pancreatic insufficiency.

CFTR stands for Cystic Fibrosis Transmembrane Conductance Regulator. It is an ATP‑gated ion channel in the ABC transporter family that controls chloride and bicarbonate transport across epithelial cell membranes in lungs, pancreas, intestines and sweat glands. Mutations in the CFTR gene disrupt ion transport, causing thick secretions, recurrent lung infections, pancreatic insufficiency and the features of cystic fibrosis.

"Delta F508" (ΔF508) denotes a deletion of the amino acid phenylalanine (one-letter code F) at position 508 of the CFTR protein. That single-residue loss causes misfolding, prevents proper trafficking to the cell surface, and impairs chloride channel function. ΔF508 is the most common mutation causing cystic fibrosis and underlies the disease’s characteristic mucus and lung problems.

The F508del (ΔF508) CFTR mutation is classified as a class II defect. It causes abnormal protein folding and defective processing in the endoplasmic reticulum, leading to proteasomal degradation and markedly reduced CFTR at the cell surface. The resulting loss of functional chloride channels produces the characteristic ion transport defect in cystic fibrosis; the mutant protein may also show residual gating and stability defects.

The ΔF508 CFTR mutation (especially in homozygous form) causes classic cystic fibrosis. With modern multidisciplinary care and CFTR modulator therapies, many people with ΔF508 live into their 40s–60s; median survival in high‑income countries commonly falls in the mid‑40s to mid‑50s. Individual prognosis varies widely with genotype, lung function, infections, nutrition, and access to specialist treatments.

Cystic fibrosis is classified by CFTR mutation effects into five types: Class I — no functional CFTR produced; Class II — protein misfolding/trafficking defect (e.g., F508del); Class III — defective gating/regulation; Class IV — reduced ion conductance; Class V — reduced protein quantity from splicing or promoter defects. They influence disease severity and treatment selection, including mutation-specific drugs.