CFTR is a protein essential to wet surfaces throughout your body, like the airways of your lungs. People with cystic fibrosis have a gene mutation that causes problems with the protein. Some medications may improve CFTR function.
Cystic fibrosis (CF) affects about 70,000 people globally. It’s due to a genetic mutation that affects the production or function of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an essential protein in several systems of your body, so its dysfunction can have severe effects.
The median life expectancy for someone with CF in the United States is about
Keep reading to learn more about what CFTR does, how it’s different in people with CF, and how medications can help counter these problems.
CFTR is a type of protein called an ion channel. That means it allows specific ions (charged particles) to pass through. Ion channels sit in cell membranes (the outer layer of cells) and allow specific ions to enter or exit the cell.
CFTR controls the passage of chloride ions in and out of cells in any organ in your body that makes mucus. These include your:
- lungs
- pancreas
- sweat glands
- liver
- salivary glands
- gastrointestinal tract
- reproductive system
- immune cells
It’s important for chloride to exit a cell and rest on the cell membrane, where it can attract water. This is especially important in the cells in your lung airways, which need a certain amount of moisture to function properly.
But CFTR also controls the passage of
CFTR may also exist in organelles, the small parts inside of cells. This means CFTR may also play a role in some
CF is due to a mutation in the CFTR gene, which codes for the CFTR protein. Mutations in this gene can cause problems with how the CFTR protein works. Researchers have discovered more than
Some mutations may cause the protein not to function properly. Others may cause you to produce too little of the protein or even none at all.
Scientists group the types of problems with CFTR into
| Class | Mutation example | Effect |
|---|---|---|
| 1 | G542X | Your cells don’t make CFTR. |
| 2 | Delta F508 | CFTR can’t get to the cell membrane. |
| 3 | G551D | CFTR doesn’t work. |
| 4 | R117H | CFTR works, but not as well as it should. |
| 5 | A455E | Your cells don’t make enough CFTR. |
| 6 | Q1412X | CFTR doesn’t live as long in the cell membrane. |
Classes 1, 2, and 3 usually result in more severe symptoms. Classes 4, 5, and 6 typically result in milder symptoms.
About
CFTR: Gene vs. protein
Because the protein and gene share a name, we typically use italics to indicate the gene. If you see CFTR (in italics) in this document, we’re talking about the gene. Otherwise, we’re referring to the protein.
CF can affect any wet surface in your body. But for people with CF, the most significant effect is on their lungs.
The airways of your lungs are lined with mucus. This mucus helps to trap bacteria and other irritants, protecting you from infection. The airways are also lined with cilia, little hair-like structures that sweep away the trapped particles, sending them out of your airways.
Reduced CFTR function causes less chloride to make it to the surface of the cells in your airways. This means they attract less water. The mucus on the outer layer becomes dehydrated and thicker.
The cilia can’t perform their sweeping action through the thickened mucus. The thick, trapped mucus makes it difficult to breathe. Bacteria in the mucus also make you more prone to infection.
Your pancreas creates enzymes that help you digest food. The tubes that transport these enzymes to your intestines are also lined with mucus. CFTR dysfunction causes thick mucus to block these tubes, resulting in several consequences.
You may not digest food properly (malabsorption), and your pancreas might become inflamed (pancreatitis). It can also prevent you from producing insulin, which can lead to
A healthy pancreas also sends bicarbonate to your stomach to help neutralize stomach acid. CFTR dysfunction can hinder this process, causing digestive problems.
Sweat glands
Your sweat glands secrete salt and water through sweat ducts and out onto the surface of your skin. The sweat ducts typically reabsorb some of this salt. This reabsorption doesn’t occur without working CFTR, leading to very salty sweat.
Liver, bile ducts, and gallbladder
CFTR is usually present in bile duct cells in your liver. Without functioning CFTR, mucus buildup can block the bile ducts. This can lead to the formation of gallstones. It can also cause inflammation that leads to scarring (cirrhosis).
Bone
CFTR also plays a role in signaling pathways that contribute to bone formation. This may cause people with CF to have lower bone density.
CF-related bone disease may also be due to a lack of vitamin D, vitamin K, or calcium from malabsorption.
Immune system
Research from 2020 suggests that CFTR dysfunction can cause certain immune cells, like neutrophils and macrophages, to be ineffective. This leaves you susceptible to allergens and infections.
Reproductive system
In people assigned male at birth, CFTR dysfunction can cause mucus to block the vas deferens. That’s the tube that carries sperm from your testes to your urethra, which ejaculates it.
The blockage causes a condition called congenital bilateral absence of the vas deferens (CBAVD). CBAVD results in infertility since your semen doesn’t contain any sperm.
In people assigned female at birth, CFTR dysfunction could thicken mucus in your cervix. It can also affect the lining of the uterus. Both of these events can make it more challenging to become pregnant.
There’s no cure for CF, but people with CF typically take several medications to help manage symptoms. Some of these medications, known as CFTR modulators, work to improve CFTR function.
The Food and Drug Administration (FDA) approved ivacaftor (Kalydeco) as the first CFTR modulator in 2012. Ivacaftor helps CFTR transport chloride. This fixes a problem due to the G551 mutation, which only affects about 10% of U.S. people with CF.
Other CFTR modulators help to fix the shape of the CFTR protein, allowing more of the protein to reach the cell membrane. Known as correctors, these help to address the more common delta F508 mutation. CFTR correctors include:
- lumacaftor
- tezacaftor
- elexacaftor
According to 2022 research, these modulators are now available to help about 85% of people with CF over the age of 12.
Available therapies as of April 2023 include:
- Trikafta (elexacaftor, tezacaftor, and ivacaftor)
- Symdeko (tezacaftor and ivacaftor)
- Orkambi (lumacaftor and ivacaftor)
But like most medications, there’s a risk of side effects from CFTR modulators. And these are lifelong medications.
Still,
Even if you don’t have CF, you may still carry a CFTR mutation. This means you can pass it down to the next generation. People who inherit a CFTR mutation from both parents will have CF.
Genetic testing, aka carrier testing, can let you know if you carry one of the mutations that can cause CF. The standard test uses a blood, saliva, or cheek swab sample to check your DNA for
A positive test result means you have a
U.S. newborns typically undergo screening for CF within their first 3 days of life.
People with CF have a gene mutation that causes a problem with the CFTR protein in their cells. Thousands of mutations can affect CFTR, but the most common one causes it to have a strange shape, preventing it from getting to the surface of cells where it does its job.
CFTR mutations affect several organs and systems in your body. The effect is usually most significant on your lungs, but it can also affect your pancreas, sweat glands, and other systems. New medications can help improve CFTR function in people with CF and reduce symptoms.
Four CFTR modulators are currently on the market, but more are in clinical trials. Talk with a doctor about whether any prospective CFTR modulators — or other treatments that try to make up for CFTR dysfunction — might help you.
Even if you don’t have CF, you may still carry a gene mutation that can cause it. Talk with a doctor about genetic testing to learn more about your risk of passing it on.