Defective CYP21A2 does not 21-hydroxylate PROG

Stable Identifier
Reaction [transition]
Homo sapiens
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Steroid 21-hydroxylase (CYP21A2) specifically catalyses the 21-hydroxylation of steroids which is required for the adrenal synthesis of mineralocorticoids and glucocorticoids. Defects in CYP21A2 can cause adrenal hyperplasia 3 (AH3; MIM:201910), a form of congenital adrenal hyperplasia (CAH) where cortisol synthesis is defective. This results in increased ACTH levels, causing overproduction and accumulation of cortisol precursors, particularly 17-hydroxyprogesterone (17HPROG). The resultant excessive production of androgens causes virilization. The most severe form of CAH caused by CYP21A2 is known as salt-wasting (SW), which is due to complete or almost complete loss of enzymatic activity. CYP21A2 mutations causing SW include G292S, V237E, Q318*, W406*, E380D (Wedell et al. 1992, White et al. 1998, Robins et al. 2005, Wedell & Luthman 1993, Kirby-Keyser et al. 1997).
Literature References
PubMed ID Title Journal Year
3267225 Nonsense mutation causing steroid 21-hydroxylase deficiency

New, MI, Amor, M, White, PC, Globerman, H, Parker, KL

J. Clin. Invest. 1988
15623806 Not all amino acid substitutions of the common cluster E6 mutation in CYP21 cause congenital adrenal hyperplasia

Wedell, A, Barbaro, M, Lajic, S, Robins, T

J. Clin. Endocrinol. Metab. 2005
9067760 E380D: a novel point mutation of CYP21 in an HLA-homozygous patient with salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Donohoue, PA, Kirby-Keyser, L, Porter, CC

Hum. Mutat. 1997
1496017 Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations

Luthman, H, Ritzén, EM, Wedell, A, Haglund-Stengler, B

Proc. Natl. Acad. Sci. U.S.A. 1992
8518786 Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations

Luthman, H, Wedell, A

Hum. Mol. Genet. 1993
Catalyst Activity

steroid 21-monooxygenase activity of CYP21A2 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP21A2 mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
adrenal gland disease DOID:9553
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