CYP21A2 (Steroid 21-hydroxylase) variants and mutations

CYP21A2 (also known as Steroid 21-hydroxylase) is a human protein-coding gene encoding a steroid 21-hydroxylase protein. It enables cortisol and aldosterone synthesis by 21-hydroxylating adrenal steroid precursors. Biallelic loss-of-function variants cause congenital adrenal hyperplasia, with cortisol deficiency, androgen excess, and in severe forms life-threatening salt wasting. This analysis covers 1,209 CYP21A2 variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, congenital adrenal hyperplasia, and hereditary disease. Example CYP21A2 variants include M1V, L2P, and L2Q.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CYP21A2 variants

Examples include M1V, L2P, L2Q, L2R, L2V, L2L, L3F, L3I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.