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Protein / target

Steroid 21-hydroxylase

Encoded byCYP21A2P08686Homo sapiensSwiss-Prot
UniProt: P08686Ensembl: ENSG00000206338HGNC: HGNC:2600NCBI Gene: 1589
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

17-hydroxyprogesterone 21-hydroxylase

Strongest disease association

Adrenal Hyperplasia, Congenital

Via encoding gene CYP21A2 · Genetic evidence · score 0.89

Research activity

Emerging research

1 papers · latest 2022

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis.

View complete UniProt function annotation

A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids (PubMed:10602386, PubMed:16984992, PubMed:22014889, PubMed:25855791, PubMed:27721825). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:25855791)

Subcellular location

Endoplasmic reticulum membraneMicrosome membrane
Domains and Gene Ontology detail (14)

Gene Ontology

  • Cendoplasmic reticulum membrane
  • F17-hydroxyprogesterone 21-hydroxylase activity
  • Fheme binding
  • Firon ion binding
  • Fprogesterone 21-hydroxylase activity
  • Fsteroid 21-monooxygenase activity
  • Fsteroid binding
  • Fsteroid hydroxylase activity
  • Pcortisol biosynthetic process
  • Pglucocorticoid biosynthetic process
  • Pmineralocorticoid biosynthetic process
  • Psteroid biosynthetic process

495 aa · 56 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·sterol metabolic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CYP21A2

Gene-level evidence surfaced through the gene CYP21A2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Adrenal Hyperplasia, Congenital
0.90Well supported

Genetic evidence dominant · Open Targets 0.56

Genetic Diseases, Inborn
0.81Well supported

Genetic evidence dominant · Open Targets 0.49

Hypersensitivity
0.41Limited support

Genetic evidence dominant · Open Targets 0.25

Adrenal gland disorder
0.24Preliminary

Pathway evidence dominant · Open Targets 0.37 · no direct causal or clinical evidence

View evidence synthesis (4)
Adrenal Hyperplasia, CongenitalWell supported
0.90
agreement 0.76–1.00
Genetic90%Literature10%

Open Targets aggregate 0.56 · 2 independent evidence families

Genetic Diseases, InbornWell supported
0.81
agreement 0.67–0.95
Genetic99%Literature1%

Open Targets aggregate 0.49 · 2 independent evidence families

HypersensitivityLimited support
0.41
agreement 0.29–0.53
Genetic100%

Open Targets aggregate 0.25 · 1 independent evidence family

Adrenal gland disorderPreliminary
0.24
agreement 0.01–0.47
Pathway100%

Open Targets aggregate 0.37 · 1 independent evidence family · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Adrenal Hyperplasia, Congenital0.56
Genetic Diseases, Inborn0.49
Adrenal gland disorder0.37
Hypersensitivity0.25

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2022

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management.304 cites

Claahsen-van der Grinten HL · Endocrine reviews · 2022

Recent

Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management.

Claahsen-van der Grinten HL · Endocrine reviews · 2022

Europe PMC papers linked directly to this protein.