Defective CYP1B1 does not 4-hydroxylate EST17b

Stable Identifier
Reaction [transition]
Homo sapiens
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Cytochrome P450 1B1 (CYP1B1) can oxidise a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics as well as activating a range of procarcinogens. A specific substrate is the female sex hormone estradiol-17beta (EST17b) which is 4-hydroxylated to 4-hydroxyestradiol-17beta 4OH-EST17b) (Badawi et al. 2001). Defects in CYP1B1 can cause glaucoma disorders such as Glaucoma 3, primary congenital, A (GLC3A; MIM:231300), Glaucoma, primary open angle (POAG; MIM:137760), Glaucoma 1, open angle, A (GLC1A; MIM:137750) and Peters anomaly (PAN; MIM:604229). These disorders cause a progressive optic neuropathy characterised by visual field defects that ultimately lead to irreversible blindness. Common mutations causing GLC3A include G61E, E387K, R368H, R390H and R469W (Bejjani et al. 1998, Plasilova et al. 1999, Vincent et al. 2002, Passuto et al. 2010). A loss-of-function mutation causing POAG is P52L (Passuto et al. 2010). A mutation causing GLC1A is V432L (Vincent et al. 2002). Mutations causing PAN are M1T and W57* (Vincent et al. 2001).
Literature References
PubMed ID Title Journal Year
9463332 Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia

Jabak, M, Otterud, B, Astle, WF, Lewis, RA, Dueker, DK, Leppert, M, Tomey, KF, Bejjani, BA, Lupski, JR, Anderson, KL

Am. J. Hum. Genet. 1998
19643970 Heterozygous loss-of-function variants in CYP1B1 predispose to primary open-angle glaucoma

Michels-Rautenstrauss, K, Fernández-Martínez, L, Rautenstrauss, B, Ingelman-Sundberg, M, Mardin, CY, Pasutto, F, Weber, BH, Reis, A, Chavarria-Soley, G

Invest. Ophthalmol. Vis. Sci. 2010
11774072 Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene

Trope, G, Vincent, AL, Buys, Y, Billingsley, G, Levin, AV, Williams-Lyn, D, Héon, E, Priston, M

Am. J. Hum. Genet. 2002
11403040 Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly

Heathcote, G, Walter, MA, Vincent, A, Sutherland, J, Williams-Lyn, D, Priston, M, Héon, E, Billingsley, G, Levin, A, Oliver, E, Glaser, T

J. Med. Genet. 2001
11555828 Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16alpha-hydroxylation of 17beta-estradiol

Badawi, AF, Cavalieri, EL, Rogan, EG

Metabolism 2001
10227395 Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma

Ferák, V, Stoilov, I, Feráková, E, Plásilová, M, Kádasi, L, Sarfarazi, M

J. Med. Genet. 1999
Catalyst Activity

monooxygenase activity of CYP1B1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of CYP1B1 mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
glaucoma DOID:1686
primary congenital glaucoma DOID:0050593
open-angle glaucoma DOID:1067 Open-angle glaucoma, unspecified, Open-angle glaucoma NOS (disorder), Glaucoma simplex, Pigmentary glaucoma (disorder), Pigmentary glaucoma, Open Angle Glaucoma, Open-angle glaucoma, Unspecified open-angle glaucoma (disorder), Pigmentary glaucoma, Wide-angle glaucoma NOS, Open-angle glaucoma (disorder)
primary open angle glaucoma DOID:1070 primary open angle glaucoma, primary Open Angle Glaucoma, chronic simple glaucoma, primary open-angle glaucoma
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