CYP21A2

The CYP21A2 gene provides instructions for making an enzyme called steroid 21-hydroxylase, which is part of the cytochrome P450 family of enzymes. Cytochrome P450 enzymes are involved in many processes in the body, such as assisting with reactions that break down drugs and helping to produce cholesterol, certain steroid hormones, and fats (lipids). Steroid 21-hydroxylase enables the adrenal glands, which are located on top of the kidneys, to convert cholesterol into other steroid hormones, specifically cortisol and aldosterone. Cortisol helps maintain blood sugar levels, protects the body from stress, and suppresses inflammation. Aldosterone, sometimes called the salt-retaining hormone, acts on the kidneys to regulate the levels of salt and water in the body, which affect blood pressure. Precursor molecules that are formed in the pathway leading to these two steroid hormones can be converted into male hormones called androgens. Androgens are normally responsible for the appearance of secondary sex characteristics in males (virilization).

21-hydroxylase deficiency - caused by mutations in the CYP21A2 gene

Mutations in the CYP21A2 gene are often caused by exchanges of DNA between the CYP21A2 gene and a very similar but nonfunctional piece of DNA called a pseudogene. Some of these exchanges can produce large or small deletions of DNA within the CYP21A2 gene. Other mutations result in a change in the building blocks (amino acids) that make up the 21-hydroxylase enzyme. In some cases, rearrangements within the gene scramble the instructions for making the enzyme, leading to an altered version of steroid 21-hydroxylase.

Mutations that delete all or part of the gene are among the most serious and may result in the production of little or no enzyme. Other mutations lead to the production of an abnormally sized protein that may not be functional. These mutations are most often associated with the salt-loss type of 21-hydroxylase deficiency. Mutations that less severely affect the structure or production of the enzyme have variable effects on the level of enzyme activity. These mutations account for the classic virilizing and nonclassic types of 21-hydroxylase deficiency.