Cytochrome P450 21A2 (CYP21A2)

Cytochrome P450 21A2 (CYP21A2) is a membrane-associated enzyme of the cytochrome P450 superfamily that serves as the "major steroid 21-hydroxylase" in humans. It catalyzes the hydroxylation of progesterone and 17α-hydroxyprogesterone to yield precursors for aldosterone and cortisol synthesis respectively. Mutations in the CYP21A2 gene account for approximately 95% of cases of "congenital adrenal hyperplasia (CAH)", a group of disorders of adrenal steroid biosynthesis characterized by adrenal insufficiency and androgen excess. The enzyme’s functional importance has been elucidated through X-ray crystallography, kinetic, and mutational analyses—where disease-causing mutations impact the active site conformation, substrate binding, and catalytic rates. While direct pharmacological inhibition is uncommon and not clinically exploited, genetic deficiency is managed by hormone replacement therapies. 17α-hydroxyprogesterone levels are used as a diagnostic and monitoring biomarker. There are significant clinical safety concerns related to CYP21A2 deficiency, including potentially life-threatening adrenal crisis due to salt wasting and cortisol deficiency.

Other names

Steroid 21-hydroxylaseCYP21P450c21

Catalysis of 21-hydroxylation of steroid precursors such as progesterone and 17α-hydroxyprogesterone, a key step in the biosynthesis of mineralocorticoids and glucocorticoids