Cystic Fibrosis - Gene Mutations and CFTR protein

Article Index
Cystic Fibrosis
Pediatrician Visit
CF Center Visit
Dietitian Visit
Gene Mutations and CFTR protein
Disease Outcome
Assessment and Diagnosis
Additional Visits with the Dietitian
CF Center Visit age 5 Years
Case Conclusion
All Pages

Located on human chromosome 7, the CFTR gene is made up of 250,000 DNA nucleotides. CFTR stands for Cystic Fibrosis Transmembrane Conductance Regulator. The CFTR protein functions as a channel for the movement of chloride ions in and out of cells, which is important for the salt and water balance on epithelial surfaces, such as in the lungs or pancreas. Changes in the CFTR gene can affect the structure of the CFTR protein.

As in every human gene, the DNA sequence is transcribed into a messenger molecule called mRNA. The CFTR gene has 27 segments called exons that are spliced together to make the complete mRNA message. The mRNA message is then translated into a chain of amino acids. This amino acid chain folds up into the correct 3-dimensional shape to produce CFTR protein, which can then sit correctly in the cell memane and function as an ion channel.

In cystic fibrosis, mutations affect the composition of the mucus layer lining the epithelial surfaces in the lungs and pancreas. The disruption of ion transport affects the salt concentration in sweat which is used in the CF “sweat test.”

Well over one thousand mutations have been described that affect the CFTR gene in different ways. The most common CFTR mutation is a deletion of just three DNA nucleotides, which leads to the deletion of an amino acid (phenylalanine) at position 508 of the protein sequence. This is denoted as ΔF508, and is found in around 90% of CF patients.

The disease spectrum has broadened as it has become clear that there are a large number of CFTR mutations. Some conditions caused by two CFTR mutations might cause only mild lung disease with or without affecting the pancreas – these conditions can be described as “atypical CF.”

Other conditions do not meet the usual diagnostic criteria for classical CF and can be referred to as “CF-related disease,” for example congenital bilateral absence of the vas deferens, which can cause sterility in males.

Though the biological effects of many CFTR mutations are known, there continue to be mutations for which scientists have incomplete knowledge of the health effects (Moskowitz S et al. 2008).

Table 1: Mutations can be grouped into classes according to their effect on the CFTR protein


Effect on CFTR protein

Example of mutation

% CF patients (Europe)

I Shortened protein W1282X Instead of inserting the amino acid tryptophan (W), the protein sequence is prematurely stopped (indicated by an X). 7
II Protein fails to reach cell membrane ΔF508 A phenylalanine amino acid (F) is deleted 85
III Channel cannot be regulated properly G551D A “missense” mutation: instead of a glycine amino acid (G), aspartate (D) is added <3
IV Reduced chloride conductance R117H Missense <3
V Reduced due to incorrect splicing of gene 3120+1G>A Splice-site mutation in gene intron 16 <3

  1. Class I, II and III mutations generally lead to complete loss of function and a more severe disease.
  2. Class IV and V cause a reduction in function and have a milder effect.

Table modified from Peebles et al.2005.

Quick Quiz

Different mutations in the same gene may cause different phenotypes (clinical outcomes) because

A. Some types of mutation affect the size of a protein chain. B. Some types of mutations affect the amount of protein made. C. Some types of mutations affect the functionality of a protein made. D. Some types of mutations cause no protein to be made at all. E. All of the above.