Defective CYP17A1 does not cleave 17aHPROG

Stable Identifier
Reaction [transition]
Homo sapiens
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Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) mediates both 17-alpha-hydroxylase and 17,20-lyase activity, allowing the adrenal glands and gonads to synthesise both 17-alpha-hydroxylated glucocorticoids and sex steroids respectively (Kagimoto et al. 1998). Defects in CYP17A1 can cause Adrenal hyperplasia 5 (AH5), a form of congenital adrenal hyperplasia (CAH), a common recessive disease due to defective synthesis of cortisol and sex steroids. Mutations causing combined 17-alpha-hydroxylase/17,20-lyase deficiency include S106P, R96W, W17*, R362C, W406R and R96Q (Lin et al. 1991, Laflamme et al. 1996, Suzuki et al. 1998, Martin et al. 2003, Brooke et al. 2006). Mutations causing isolated 17,20-lyase deficiency are R358Q and R347H (Geller et al. 1997, Van den Akker et al. 2002).
Literature References
PubMed ID Title Journal Year
14671162 P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping

Martin, RM, de Oliveira, ML, Costa, EM, Villar, H, Lin, CJ, Longui, CA, Carrilho, A, Mendonca, BB

J. Clin. Endocrinol. Metab. 2003
16569739 A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17,20-lyase deficiency

Auchus, RJ, Achermann, JC, Papari-Zareei, M, Gore, ME, Ahmad, T, Taylor, NF, Brooke, AM, Monson, JP, Rumsby, G, Shepherd, JH, Lin, L

J. Clin. Endocrinol. Metab. 2006
9326943 The genetic and functional basis of isolated 17,20-lyase deficiency

Miller, WL, Auchus, RJ, Mendonça, BB, Geller, DH

Nat. Genet. 1997
9435441 A new compound heterozygous mutation (W17X, 436 + 5G --> T) in the cytochrome P450c17 gene causes 17 alpha-hydroxylase/17,20-lyase deficiency

Suzuki, Y, Nagashima, T, Nagashima, K, Nomura, Y, Morikawa, A, Onigata, K

J. Clin. Endocrinol. Metab. 1998
8550762 Mutation R96W in cytochrome P450c17 gene causes combined 17 alpha-hydroxylase/17-20-lyase deficiency in two French Canadian patients

Leblanc, JF, Mailloux, J, Labrie, F, Simard, J, Faure, N, Laflamme, N

J. Clin. Endocrinol. Metab. 1996
2843762 Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency

Waterman, MR, Winter, JS, Kagimoto, M, Kagimoto, K, Simpson, ER

Mol. Endocrinol. 1988
12466376 Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency

Themmen, AP, De Jong, FH, Timmerman, MA, Otten, BJ, Drop, SL, Boehmer, AL, Verhoef-Post, M, Koper, JW, Van Den Akker, EL

J. Clin. Endocrinol. Metab. 2002
1714904 Missense mutation serine106----proline causes 17 alpha-hydroxylase deficiency

Miller, WL, Harikrishna, JA, Jones, KL, Moore, CC, Lin, D

J. Biol. Chem. 1991
Catalyst Activity

steroid 17-alpha-monooxygenase activity of CYP17A1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP17A1 mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
adrenal gland disease DOID:9553
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