Cftr
From DrugPedia: A Wikipedia for Drug discovery
Cystic fibrosis transmembrane conductance regulator (CFTR) is an ABC transporter-class protein and ion channel that transports chloride ions across epithelial cell membranes. Mutations of the CFTR gene affect functioning of the chloride ion channels in these cell membranes, leading to cystic fibrosis and congenital absence of the vas deferens
The CFTR is found in the epithelial cells of many organs including the lung, liver, pancreas, digestive tract, reproductive tract, and skin. Normally, the protein moves chloride ions (with a negative charge) out of an epithelial cell to the covering mucus. This results in an electrical gradient being formed and in the movement of (positively charged) sodium ions in the same direction as the chloride via a paracellular pathway. Due to this movement, the water potential of the mucus is reduced, resulting in the movement of water here by osmosis and a more fluid mucus.
CFTR (cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7)) is a human gene that provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. This protein functions as an ion channel across the cell membrane. Such channels are found in tissues that produce mucus, sweat, saliva, tears and digestive enzymes. Chloride, a component of salt, is transported through the channels in response to cellular signals. The transport of chloride helps control the movement of water (osmosis) in tissues and maintain the fluidity of mucus and other secretions. The CFTR protein also regulates the function of other channels, such as a type of channel that transports sodium across cell membranes. Normal functioning of these channels ensures that organs such as the lungs and pancreas function properly.
The CFTR gene is located on the long (q) arm of chromosome 7 at position 31.2, from base pair 116,907,253 to base pair 117,095,955.
Genes in the ATP-binding cassette (ABC) family provide instructions for making transporter proteins that carry many types of molecules, such as fats, sugars, protein building blocks (amino acids) and drugs, across cell membranes. In most cases, the transporters move the molecules into specific cell compartments so they can be processed, or out of the cell so they can be used elsewhere or excreted from the body. If the molecules are not transported properly, they may be unavailable where they are needed for body functions. The molecules can also build up over time and damage the cells.
ABC transporter proteins are made in many tissues of the body, and use energy from a molecule called ATP to move substances across the cell membranes. They are grouped together because they all have common structures (domains) that bind to ATP.
Cystic fibrosis: More than 1,000 mutations in the CFTR gene have been found but the majority of these have not been associated with cystic fibrosis. Most of these mutations either substitute one amino acid (a building block of proteins) for another amino acid in the CFTR protein or delete a small amount of DNA in the CFTR gene. The most common mutation, called ΔF508, is a deletion (Δ) of one amino acid at position 508 in the CFTR protein. This altered protein never reaches the cell membrane because it is degraded shortly after it is made. All disease-causing mutations in the CFTR gene prevent the channel from functioning properly, leading to a blockage of the movement of salt and water into and out of cells. As a result of this blockage, cells that line the passageways of the lungs, pancreas, and other organs produce abnormally thick, sticky mucus. This mucus obstructs the airways and glands, causing the characteristic signs and symptoms of cystic fibrosis. In addition, thin mucus can be removed by cilia. However, thick mucus cannot be removed by cilia, so it traps bacteria that give rise to chronic infections
Congenital bilateral absence of vas deferens: Males with congenital bilateral absence of the vas deferens most often have a mild mutation (a change that allows partial function of the gene) in one copy of the CFTR gene and a cystic fibrosis-causing mutation in the other copy of CFTR. As a result of these mutations, the movement of water and salt into and out of cells is disrupted. This disturbance leads to the production of a large amount of thick mucus that blocks the developing vas deferens (a tube that carries sperm from the testes) and causes it to degenerate, resulting in infertility
