ABCA1

The ABCA1 gene belongs to a group of genes called the ATP-binding cassette family, which provides instructions for making proteins that transport molecules across cell membranes. The ABCA1 protein is produced in many tissues, but especially in the liver and in immune system cells called macrophages. This protein moves cholesterol and other types of fats, known as phospholipids, across the cell membrane to the outside of the cell. These substances are then picked up by a protein called apolipoprotein A1 (apoA1) that circulates in the bloodstream. ApoA1 is used to make high-density lipoproteins (HDL), often referred to as "good cholesterol." High-density lipoproteins carry cholesterol from the body's tissues to the liver for elimination through bile, a yellow substance made by the liver that aids in the digestion of fats. The process of removing excess cholesterol from the cells and transporting it to the liver for removal is extremely important for the balance (homeostasis) of cholesterol and the health of the heart and blood vessels (cardiovascular health).

Tangier disease - caused by mutations in the ABCA1 gene

More than 30 mutations that cause Tangier disease have been identified in the ABCA1 gene. Almost all of these mutations substitute one amino acid (a protein building block) for another amino acid in the ABCA1 protein. These mutations prevent the ABCA1 protein from effectively transporting cholesterol and phospholipids out of cells for pickup by ApoA1 in the bloodstream. This inability to transport cholesterol out of cells leads to a deficiency of high-density lipoproteins in the circulation, which is a risk factor for cardiovascular disease. Additionally, the buildup of cholesterol in cells can be toxic, causing cell death or impaired function. These combined factors lead to the signs and symptoms of Tangier disease.

other disorders - caused by mutations in the ABCA1 gene

Mutations in the ABCA1 gene are also responsible for a condition called familial high-density lipoprotein deficiency or hypoalphalipoproteinemia. People affected by familial high-density lipoprotein deficiency have reduced levels of high-density lipoproteins in their blood, but do not accumulate cholesterol inside their cells as is seen in Tangier disease. People with this disorder may experience premature cardiovascular disease, however.