Defective CFTR protein
CFTR proteins don’t work correctly in people with cystic fibrosis
Although we know of over 2,000 different mutations in the CFTR gene, only 281 of these cause cystic fibrosis (CF) and most of them are extremely rare.
Different CFTR mutations can have different effects on CFTR proteins:
- Some mutations lead to decreased numbers of CFTR proteins at the cell surface (reduced quantity)
- Other mutations lead to CFTR proteins that don’t work correctly at the cell surface (reduced function)
- Finally, some mutations can lead to a reduction in both the quantity and the function of CFTR proteins
Reduced CFTR protein function
When CFTR proteins don’t work correctly, the channels on the cell surface don’t stay open for as long as a normal CFTR protein channel does, or they don’t open as often as a normal channel does.
CFTR proteins not working correctly (reduced function)
Reduced CFTR protein quantity
When there are not enough CFTR proteins at the cell surface, this can be due to gene mutations that cause:
- The CFTR protein channels to be made incorrectly
- The instructions for making CFTR proteins to be read incorrectly by the parts of the cell that build the CFTR protein
- Faulty CFTR proteins to be produced that are destroyed by the cell before they reach the cell surface
- Unstable CFTR proteins to be made, which are removed too quickly from the cell surface
The F508del mutation, the most common CFTR mutation worldwide, causes a decreased number of CFTR protein channels at the cell surface.
Too few CFTR proteins (reduced quantity)
What does this all mean?
Having too few CFTR proteins at the cell surface and/or CFTR proteins that don’t work correctly means that water and molecules such as chloride ions cannot move freely in and out of your cells.
The end result is that the balance of salt and water in your organs is no longer correct, which can cause your mucus to become thick and sticky. Thick and sticky mucus stops your organs (lungs and other parts of the body) from working properly and leads to the symptoms of CF.
US CF Foundation, Johns Hopkins University, The Hospital for Sick Children. The Clinical and Functional Translation of CFTR (CFTR2). 13th August 2015. Available at: http://www.cftr2.org/files/CFTR2_13August2015.pdf.
Orenstein DM. Cystic Fibrosis: A Guide for Patient and Family. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004.
Welsh M, Smith A. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 1993; 73(7): 1251–1254.