What is the function of the cftr gene?

The CFTR protein The cystic fibrosis transmembrane conductance regulator (CFTR) protein is responsible for regulating the proper flow of chloride and sodium (a component of salt) in and out of the cell membranes in the lungs and other organs. is made up of 1,480 amino acids.

Where is the CFTR gene?

The gene that encodes the CFTR protein, which is also called CFTR, is located on chromosome 7. Mutations in this gene lead to CF.

What is the CFTR protein What is its structure?

The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function.

How does CFTR cause cystic fibrosis?

Summary. Cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In people with CF, mutations in the CFTR gene can disrupt the normal production or functioning of the CFTR protein found in the cells of the lungs and other parts of the body …

What chromosome is the CFTR gene on?

Although there have been numerous reports from around the world of mutations in the gene of chromosome 7 known as CFTR (cystic fibrosis transmembrane conductance regulator), little attention has been given to integrating these mutant alleles into a global understanding of the population molecular genetics associated …

What is the CFTR transporter?

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated anion channel with two remarkable distinctions. First, it is the only ATP-binding cassette (ABC) transporter that is known to be an ion channel—almost all others function as transport ATPases.

How do CFTR modulators work?

CFTR modulators target the defective proteins and work to control their effects by moving them to the cell surface and helping them function properly. Drugs are designed to target proteins based on specific CFTR gene mutations. These drugs currently are available in oral tablet form.

How was the CFTR gene discovered?

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene was identified in 1989 by geneticist Lap-Chee Tsui and his research team as the gene associated with cystic fibrosis (CF). Tsui’s research pinpointed the gene, some mutations to which cause CF, and it revealed the underlying disease mechanism.

How is CFTR regulated?

The anion-selective pore of the CFTR protein is formed by its two transmembrane domains (TMDs) and regulated by its cytosolic domains: two nucleotide binding domains (NBDs) and a regulatory (R) domain.

What happens when the CFTR gene is mutated?

Mutations in the CFTR gene disrupt the function of the chloride channel, preventing the usual flow of chloride ions and water into and out of cells. As a result, cells in the male genital tract produce mucus that is abnormally thick and sticky.

Which tissue S in CF patients need functional CFTR genes?

CFTR is found to be expressed in the epithelial cells of a variety of tissues and organs, whose functions are significantly affected in CF patients: lung and trachea, pancreas, liver, intestines, and sweat glands.

Is cystic fibrosis an autosomal dominant gene?

This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations.

When was the CFTR gene discovered?

The CF gene—its product being the cystic fibrosis transmembrane conductance regulator (CFTR), and its major mutation Delta F508 was discovered in 1989. World-wide collaboration has resulted in discovery of more than 150 further mutations.

Can CFTR protein function if it is unfolded?

During our investigations on the mechanisms of CFTR expression regulation, we have shown that the ER stress response, the unfolded protein response (UPR), decreases CFTR expression at the transcriptional, translational, and maturational levels.

How big is the CFTR gene?

CFTR gene is localized on the long arm of chromosome 7 (7q21-34), spanning approximately 190 kb of genomic DNA. The gene consists of 27 exons and encodes a mature mRNA transcript of 6.5 kb that is translated into a 1480 amino acid protein (3).

What is the function of the CFTR protein and how is the CFTR transporter an abnormal ABC transporter?

The CFTR gene codes for an ABC transporter-class ion channel protein that conducts chloride ions across epithelial cell membranes. Mutations of the CFTR gene affecting chloride ion channel function lead to dysregulation of epithelial fluid transport in the lung, pancreas and other organs, resulting in cystic fibrosis.

Is CFTR a receptor?

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel, but its relationship to the primary clinical manifestation of CF, chronic Pseudomonas aeruginosa pulmonary infection, is unclear. We report that CFTR is a cellular receptor for binding, endocytosing, and clearing P.

How does CFTR affect mucus production?

CF causes thick mucus to build up and clog certain parts of the body such as the lung. The buildup is caused by an abnormal gene called CFTR (cystic fibrosis transmembrane regulator). CFTR controls the flow of water and salt in and out of the body’s cells. Changes cause mucus to become thickened and sticky.

What is ivacaftor used to treat?

Ivacaftor is used to treat certain types of cystic fibrosis (an inborn disease that causes problems with breathing, digestion, and reproduction) in adults and children 4 months of age and older. Ivacaftor should be used only in people with a certain genetic make-up.

What is the mechanism of ivacaftor?

While the specific mechanism of action is unknown, ivacaftor is thought to restore the flow of chloride ions through the cell membrane via CFTR, and thereby reduce the symptoms of CF in patients with a gating defect.

What was the first CFTR modulator?

Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients).

What organelle does the transcription of CFTR take place in?

In most kids with cystic fibrosis, says Balch, the CFTR protein gets stuck inside the cells in a cell organelle known as the endoplasmic reticulum—a convoluted membranous sac within the cell where the synthesis of proteins like CFTR and other vital cell functions take place.

What is the function of the protein encoded by FMR1?

The FMR1 gene provides instructions for making a protein called FMRP. This protein is present in many tissues, including the brain, testes, and ovaries. In the brain, it may play a role in the development of connections between nerve cells (synapses), where cell-to-cell communication occurs.

How many base pairs is the CFTR gene?

The CFTR gene contains over 180,000 base-pairs and the protein has 1480 amino acids. Abnormalities in any of these aforementioned steps – from DNA to fully functional protein – can result in irregularity of CFTR activity and therefore the CF phenotype.

Why does CFTR need ATP?

Like other ABC transporters, CFTR uses ATP binding to its two nucleotide binding domains (NBDs) to drive conformational rearrangements of its transmembrane domains (2, 3).

Is the CFTR protein active transport?

Among human ABC proteins, CFTR is thought to be unique in that it has no active transport function, but instead acts as a phosphorylation-regulated, ATP-gated anion channel [5. The ABC protein turned chloride channel whose failure causes cystic fibrosis.

Is CFTR facilitated diffusion?

This creates an electrochemical gradient across the apical membrane, resulting in the CFTR gated channel protein opening and chloride ions diffusing out of the epithelial cells into the mucus through the CFTR channel in facilitated diffusion, down the concentration gradient.

What is the most common CFTR mutation?

The most common CF mutation, F508del, is primarily considered to be a processing mutation. The F508del mutation removes a single amino acid from the CFTR protein. Without this building block, the CFTR protein cannot stay in the correct 3-D shape.

Who discovered the link between CFTR and cystic fibrosis?

Paul di Sant’Agnese observed infants who were dehydrated. He discovered that the sweat of children with CF had abnormally high concentrations of salt. In the 1980s, the protein defect was described, and the responsible gene (CFTR) was identified and its genetic code sequenced.

How many CFTR mutations are known?

More than 1,700 mutations of the CFTR gene have been identified. Although some are common, others are rare and found in only a few people.

How does CF affect biological maturation?

Trouble with physical development, growth, and gaining weight is one of the most common problems children with cystic fibrosis face. Growing requires extra energy and nutrients in any child, but children with CF need extra calories (energy) to breathe and fight infections.

Is the CFTR gene dominant or recessive?

CF is caused by mutations in the CFTR gene and inheritance is autosomal recessive .

What does autosomal mean?

“Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the disease-associated mutation is enough to cause the disease. This is in contrast to a recessive disorder, where two copies of the mutation are needed to cause the disease.

What is autosomal biology?

An autosome is any of the numbered chromosomes, as opposed to the sex chromosomes. Humans have 22 pairs of autosomes and one pair of sex chromosomes (the X and Y). Autosomes are numbered roughly in relation to their sizes.

How many exons does the CFTR gene have?

Residing on chromosome 7q31. 3 (7) and consisting of 27 exons, the human CFTR gene encodes a 6,129-bp transcript that directs the synthesis of a 1,480-aa protein (2, 3) shown to function as a chloride channel (8–10).

What role does osmosis play in cystic fibrosis?

– Sticky mucus traps bacteria and causes more lung infections. Therefore, because of less diffusion of salt and less osmosis of water, people with cystic fibrosis have too much sticky mucus in the airways of their lungs and get lots of lung infections.