Cystic fibrosis is caused by a mutation in the cystic fibrosis trans-membrane conductance regulator (CFTR) gene, which is located on the long arm (q) of chromosome 7 at position 31.2 from base pair 116,907,253 to base pair 117,095,955. The CFTR gene provides instructions for creating the CFTR protein.
Cystic fibrosis is a genetic disease caused by abnormal coding found on as many as 900 CFTR alleles, and is passed on by autosomal recessive inheritance.
There are over 1,200 different mutations cataloged so far. The most common, ΔF508 is a deletion of one amino acid at position 508. Because of this, the protein doesn’t fold properly and cannot pass through either the nuclear or the cell membrane and is broken down in the endoplasmic reticulum. Lacking the phenylalanine produced by normal proteins, it interferes with the cyclic adenosine monophosphate-regulated chloride channels and transport of other ions by preventing adenosine triphosphate from binding to the protein or by interfering with activation by protein kinase.
The CFTR protein functions as an ion channel across the membrane in endocrine glands and assists in the transmission of chloride across the membrane in volume-absorbing epithelia (in the airways and intestines), salt-absorbing epithelia (in sweat ducts), and volume-secretory epithelia (in the pancreas). Lack of phenylalanine leads to dehydration, increasing the viscosity of mucus-gland secretion, leading to obstruction of glandular ducts.