CYP27A1

The CYP27A1 gene is a member of the cytochrome P450 gene family. Enzymes produced from the cytochrome P450 genes are involved in the formation and breakdown of various molecules and chemicals within cells. The CYP27A1 gene provides instructions for producing an enzyme called sterol 27-hydroxylase. This enzyme is located in the energy-producing centers of cells (mitochondria), where it is involved in the pathway that breaks down cholesterol to form acids used to digest fats (bile acids). Specifically, sterol 27-hydroxylase breaks down cholesterol to form a bile acid called chenodeoxycholic acid. The formation of bile acids from cholesterol is the body's main pathway for cholesterol removal. Sterol 27-hydroxylase plays a key role in maintaining normal cholesterol levels in the body.

cerebrotendinous xanthomatosis - caused by mutations in the CYP27A1 gene

More than 50 mutations that cause cerebrotendinous xanthomatosis have been identified in the CYP27A1 gene. Most of these mutations change one protein building block (amino acid) in the sterol 27-hydroxylase enzyme. The most common mutation changes the amino acid arginine to the amino acid cysteine at position 362 in the protein (written as Arg362Cys or R362C). Changes in amino acids typically disrupt the normal function of the protein and impair its ability to break down cholesterol. Other mutations cause no functional enzyme to be made. The reduction or lack of functional sterol 27-hydroxylase enzyme and subsequent accumulation of cholesterol throughout the body, particularly in the brain and tendons, cause the signs and symptoms of cerebrotendinous xanthomatosis.