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[Biochemistry](https://durgical.com/en/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](https://www.enzyme-database.org/query.php?ec=1.14.14.16)

**Genes**
CYP21A2

**Structure (PDB)**
[4Y8W](https://www.rcsb.org/structure/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

- [Adrenal cortisol synthesis](https://durgical.com/en/biochemistry/pathways/adrenal-cortisol-synthesis/)

## Related conditions

- [Congenital adrenal hyperplasia due to 21-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/)
- [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/)

## Related

- [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/)
- [17-Hydroxyprogesterone (17-OHP)](https://durgical.com/en/biochemistry/molecules/17-hydroxyprogesterone/)
- [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/)
- [Aldosterone](https://durgical.com/en/biochemistry/molecules/aldosterone/)
- [11β-Hydroxylase (CYP11B1)](https://durgical.com/en/biochemistry/enzymes/11-hydroxylase/)
- [17α-Hydroxylase/17,20-lyase (CYP17A1)](https://durgical.com/en/biochemistry/enzymes/17-hydroxylase-17-20-lyase/)
- [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/)

## 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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [CYP21A2: Steroid 21-hydroxylase (human)](https://www.uniprot.org/uniprotkb/P08686/entry) (UniProt, 2026); [CYP21A2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cyp21a2/) (MedlinePlus, US National Library of Medicine, 2026); [4Y8W: Crystal Structure of Human Cytochrome P450 21A2 Progesterone Complex](https://www.rcsb.org/structure/4Y8W) (RCSB Protein Data Bank, 2026); [21-hydroxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency/) (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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