CYP21A2 Gene - Cytochrome P450 Family 21 Subfamily A Member 2
Key enzyme in adrenal steroidogenesis; mutations cause congenital adrenal hyperplasia
Gene Information Card
| Symbol | CYP21A2 |
|---|---|
| Full Name | Cytochrome P450 Family 21 Subfamily A Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 1589 ncbi.nlm.nih.gov/gene/1589 |
| Ensembl ID | ENSG00000198457 |
| UniProt ID | P08686 |
| OMIM ID | 613815 |
| HGNC ID | 2600 |
| Aliases | CYP21, CYP21B, CA21H, CAH1, P450c21B |
Description
CYP21A2 encodes the steroid 21-hydroxylase enzyme (P450c21), a member of the cytochrome P450 superfamily. This enzyme is expressed in the adrenal cortex and catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to 11-deoxycorticosterone, essential steps in cortisol and aldosterone biosynthesis. Mutations in CYP21A2 cause congenital adrenal hyperplasia (CAH), the most common form being 21-hydroxylase deficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital adrenal hyperplasia due to 21-hydroxylase deficiency | Loss-of-function mutations impair cortisol and aldosterone synthesis, leading to androgen excess | OMIM #201910; ClinVar; NCBI |
| Adrenal insufficiency, primary | Biallelic null mutations abolish enzyme activity, causing salt-wasting crisis | OMIM; ClinVar |
| Non-classic congenital adrenal hyperplasia | Mild missense mutations reduce enzyme activity by 20-50%, causing late-onset hyperandrogenism | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 78.5 | High |
| Testis | 1.2 | Low |
| Ovary | 0.8 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H295R (adrenocortical) | 85.3 | Adrenal cortex model |
| SW13 (adrenal carcinoma) | 42.1 | Moderate expression |
| HeLa | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.293-13A/C>G (IVS2-13A/C>G) | Splice site | ~30% in classic CAH | Aberrant splicing, loss of enzyme activity |
| p.Ile172Asn (I172N) | Missense | ~20% in classic CAH | Reduced activity (~2% of wild-type) |
| p.Val281Leu (V281L) | Missense | ~50% in non-classic CAH | Partial activity (~20-50%) |
| p.Gln318Stop (Q318X) | Nonsense | ~5% in classic CAH | Truncated, no activity |
| p.Arg356Trp (R356W) | Missense | ~5% in classic CAH | Severely reduced activity |
Mutation functional classification
Loss of Function (LOF)
Most CYP21A2 mutations cause partial or complete loss of 21-hydroxylase activity, leading to cortisol deficiency and androgen excess.
Gain of Function (GOF)
No gain-of-function mutations reported in CYP21A2.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Metabolic pathways (KEGG: hsa01100)
• Steroid hormone biosynthesis (KEGG: hsa00140)
• Ovarian steroidogenesis (KEGG: hsa04913)
• Cushing syndrome (KEGG: hsa04934)
Protein Summary
CYP21A2 encodes a 494-amino acid microsomal cytochrome P450 enzyme (P450c21) localized to the endoplasmic reticulum. It contains a heme-binding domain and a conserved P450 cysteine ligand. The enzyme hydroxylates steroids at position 21, critical for glucocorticoid and mineralocorticoid synthesis. Deficiency leads to accumulation of 17-hydroxyprogesterone and adrenal androgens, causing virilization and salt-wasting in severe cases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP21A2 Knockout HEK293 Cell Line | EDJ-KQ13080 | Human | 1589 | Details Get a Quote |
| CYP21A2 Knockout NCI-H295R Cell Line | EDJ-KZ174 | Human | 1589 | Details Get a Quote |
| CYP21A2 Knockout HeLa Cell Line | EDJ-KQ53062 | Human | 1589 | Details Get a Quote |
| CYP21A2 Knockout A-549 Cell Line | EDJ-KQ61528 | Human | 1589 | Details Get a Quote |
| CYP21A2 Knockout HCT 116 Cell Line | EDJ-KQ70020 | Human | 1589 | Details Get a Quote |
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