CYP21A2

CYP21A2, also known as cytochrome P450 family 21 subfamily A member 2, is a gene located on chromosome 6p21.3 that encodes the enzyme 21-hydroxylase. This enzyme plays a crucial role in the biosynthesis of corticosteroids, including cortisol and aldosterone, which are essential hormones for metabolism, immune response, and electrolyte balance.

The CYP21A2 gene is predominantly expressed in the adrenal cortex, where it catalyzes the 21-hydroxylation of progesterone and 17-hydroxyprogesterone. These reactions are critical steps in the steroidogenic pathway, facilitating the production of glucocorticoids and mineralocorticoids.

Mutations in CYP21A2 are the primary cause of congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by impaired cortisol synthesis. Depending on the specific mutations, CAH can present with varying severity, from salt-wasting crises to milder forms with virilization effects. The disorder often results in abnormal sexual development and can impair overall health if not properly managed.

CYP21A2 shares high sequence similarity with its pseudogene, CYP21A1P, which complicates genetic analysis due to potential gene conversions and recombination events. Diagnostic testing for CYP21A2 mutations is vital for early detection and management of CAH.

Research continues to explore the gene’s regulation, mutation spectrum, and role in adrenal disorders. Understanding CYP21A2 function and its genetic variations is essential for diagnosing and treating steroidogenic disorders and contributes to broader insights into adrenal gland physiology.