What are the causes of cystic fibrosis?

People have cystic fibrosis (CF) because they have inherited a faulty gene from both of their parents. Find out more about the CF gene, genotypes and the different mutations that people with CF have.


CF carrier 640x360 diagram

Cystic fibrosis can't be caught or developed. If you are not born with CF you will never have it, but you could be a CF gene carrier.

One in 25 people carry the CF gene. For someone to be born with CF, both parents must carry the faulty gene. If both parents have the gene, there is a 25% chance the child will have CF. If both parents carry the gene there is also a 50% chance of the child being a gene carrier but not having CF and a 25% chance they will not have the CF gene.

Some people with CF are not diagnosed until later in life. You can find out more about this and how CF is diagnosed here.

What is a genotype?

Everyone with CF will have two faulty or ‘mutated’ CF genes. There are over 2,000 known mutations that can cause CF, and it’s important to know which ones you have. Find out more about gene mutations by watching our video.

The two genes could be the same mutation, or you could have two different ones. The specific mutations and combination you have is known as your ‘genotype’. Your genotype will affect some of the treatments you can take. As we move into the era of precision medicines and personalised healthcare, this will become even more important.

As well as research into medicines that work for people with specific CF genotypes, research into so-called ‘genotype agnostic’ treatments that will work for everyone with CF is also underway.

Types of mutation

Genes instruct the body on how to make proteins and where to send them in cells in order for them to work. Cystic fibrosis mutations affect the body’s ability to make or direct the CFTR protein, which helps salt and water move into and out of cells. The mutations can be split into different categories depending on how they affect the CFTR protein.

The first three classes generally lead to complete loss of CFTR function and a more severe form of the disease. The last two classes cause a milder reduction in function. However, everyone with cystic fibrosis will have two faulty copies of the CFTR gene, and while these may both have the same fault (or mutation), they are often a combination of different mutations. The exact combination of mutations (your genotype) and other factors will dictate how severe the condition is for you, and which organs in the body are worst affected.

Class I – shortened protein

Around 7% of people with cystic fibrosis in Europe have this type of mutation, which results in a shortened CFTR protein.

Class II – protein fails to reach membrane

Around 85% of people with cystic fibrosis in Europe have this type of mutation, which results in the CFTR protein not being transported to the surface of the cells in which it is required. The most common of this type of mutation is F508del.

Class III – protein cannot be regulated

Less than 3% of people with cystic fibrosis in Europe have this type of mutation. The CFTR protein forms a channel in the cell surface – in people with this mutation the gate at the end of the channel doesn’t open and close at the right times.

Class IV – reduced chloride conductance

Less than 3% of people with cystic fibrosis in Europe have this type of mutation, which changes the shape of the protein channel so that chloride cannot move easily in and out of the cells.

Class V – reduced protein levels

Less than 3% of people with cystic fibrosis in Europe have this type of mutation, which results in a reduction in the amount of CFTR protein produced by the cells.

Find out more about your genotype

CFTR2 is a website that provides information about specific variants in the CF gene. If you would like to use the website you will need to read and accept the site usage agreements at the bottom of the home page. On the next page (the welcome page) you can then enter your genetic variants into the search bars at the top of the page. If you get stuck there are some video tutorials at the bottom of the welcome page guiding you through the site usage agreements and how to use the searches.

After you’ve entered your genetic variants into the search bars, you should be able to view information about the average:

  • sweat chloride in people with your genotype
  • lung function in people with your genotype
  • pancreatic insufficiency in people with your genotype
  • Pseudomonas infection rate in people with your genotype

Please remember that this information is not a substitute for information from your CF team, and is only a representation of the average health outcomes of people with your genotype, and cannot account for individual experience.

As well as searching for information on your genotype, on the ‘Resources’ section of the CFTR2 website you can take a look at information about CF variants and genotypes, and view a glossary, FAQ section and additional resources on the CFTR2 website.

Visit CFTR2

How is cystic fibrosis diagnosed?

Our page on how people with cystic fibrosis are diagnosed with the condition also includes information on newborn screening, carrier testing and late diagnosis.

How is cystic fibrosis treated?

Find out more about medication, exercise, nutrition, transplant and transition on our treatment page.

How cystic fibrosis affects the body

Explore our interactive body to find out all about the different ways CF affects the body, from the lungs and digestive system to the bones and the reproductive system.

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