Biochemistry · Enzyme
21-Hydroxylase (CYP21A2) !
An adrenal enzyme needed to make cortisol and aldosterone; its deficiency causes 95 % of congenital adrenal hyperplasia.
Updated 2026-11-01
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Key facts
- It hydroxylates carbon 21: 17-hydroxyprogesterone → 11-deoxycortisol and progesterone → 11-deoxycorticosterone.
- An endoplasmic reticulum cytochrome P450 of the fasciculata and glomerulosa; it receives electrons from P450 oxidoreductase (NADPH).
- The gene sits on chromosome 6, inside the HLA region, next to a very similar pseudogene (CYP21A1P): recombination between the two explains most mutations.
- Structure 4Y8W is human CYP21A2 with progesterone, its substrate, above the active-site haem.
- Also called
- Steroid 21-monooxygenase, P450c21
- EC number
- 1.14.14.16
- Genes
- CYP21A2
- Structure (PDB)
- 4Y8W
Regulation
- ACTH raises its expression in the fasciculata (cAMP/PKA); in the glomerulosa angiotensin II and potassium act.
- No allosteric regulation of clinical importance is known.
Inhibitors and toxins
- No selective inhibitors are in clinical use; some azole antifungals inhibit it weakly
Clinical notes
- Its deficiency piles up 17-hydroxyprogesterone, which spills into androgens: ambiguous genitalia in girls and precocious puberty.
- Severe forms lose salt in the first weeks of life because aldosterone is missing.
- The non-classic form (residual activity) is a common cause of hirsutism and is mistaken for polycystic ovaries.
Pathways
Related conditions
Related
- Adrenal enzymes and congenital adrenal hyperplasia
- 17-Hydroxyprogesterone (17-OHP)
- Cortisol
- Aldosterone
- 11β-Hydroxylase (CYP11B1)
- 17α-Hydroxylase/17,20-lyase (CYP17A1)
- Steroid hormone synthesis (overview)
Test yourself
Think of the answer, then tap the question to see it.
Which two reactions does 21-hydroxylase catalyse?
17-hydroxyprogesterone to 11-deoxycortisol and progesterone to 11-deoxycorticosterone.
Why are CYP21A2 mutations so common?
Because the gene sits next to an almost identical pseudogene, and recombination between them causes deletions and gene conversions.
Which precursor is measured in newborn screening for 21-hydroxylase deficiency?
17-Hydroxyprogesterone.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: CYP21A2: Steroid 21-hydroxylase (human) (UniProt, 2026); CYP21A2 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 4Y8W: Crystal Structure of Human Cytochrome P450 21A2 Progesterone Complex (RCSB Protein Data Bank, 2026); 21-hydroxylase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.