CYP11B1 gene

cytochrome P450 family 11 subfamily B member 1

The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme is found in the adrenal glands, which are located on top of the kidneys. The 11-beta-hydroxylase enzyme is a member of the cytochrome P450 family of enzymes. These enzymes are involved in the formation and breakdown of various molecules within cells.

The 11-beta-hydroxylase enzyme helps produce hormones called cortisol and corticosterone. Specifically, the enzyme helps convert a molecule called 11-deoxycortisol to cortisol, and helps convert another molecule called 11-deoxycorticosterone to corticosterone. These processes are triggered by the release of a hormone called adrenocorticotropic hormone (ACTH) by the pituitary gland, located at the base of the brain.

Cortisol helps maintain blood sugar levels, protects the body from physical stress, and suppresses inflammation. Corticosterone is converted to the hormone aldosterone by the aldosterone synthase enzyme, which is produced from the nearby CYP11B2 gene. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body.

More than 80 mutations in the CYP11B1 gene have been found to cause congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency, a disorder in which the adrenal glands produce excess male sex hormones (androgens). Most of these mutations change single protein building blocks (amino acids) in the 11-beta-hydroxylase enzyme and decrease the function of the enzyme. CYP11B1 gene mutations that severely reduce or eliminate the function of the enzyme typically result in the classic form of CAH due to 11-beta-hydroxylase deficiency. Mutations that allow for some enzyme function usually result in the non-classic form of the disorder.

Some mutations that cause the classic form of CAH due to 11-beta-hydroxylase deficiency fuse sections of the CYP11B1 gene with sections of a nearby gene called CYP11B2. The added part of the CYP11B2 gene contains a section called a promoter region, which normally controls (regulates) production of the protein made by the CYP11B2 gene. As a result, the CYP11B1 gene is regulated by the CYP11B2 gene promoter region rather than its own promoter region. In addition, the fusion typically deletes parts of the CYP11B1 gene. These changes in the gene's regulation and structure diminish production of 11-beta-hydroxylase.

Both types of CAH due to 11-beta-hydroxylase deficiency interfere with the production of cortisol and corticosterone. The molecules that are used to form these hormones instead build up in the adrenal gland and are converted to androgens. The excess production of androgens leads to abnormalities of sexual development in people with CAH due to 11-beta-hydroxylase deficiency. A buildup of the molecule 11-deoxycorticosterone, the substance that 11-beta-hydroxylase converts to form corticosterone, increases salt retention, leading to high blood pressure (hypertension) in individuals with the classic form of CAH due to 11-beta-hydroxylase deficiency.

A genetic change affecting the CYP11B1 gene causes familial hyperaldosteronism type I, a disorder that leads to hypertension. This change joins (fuses) a section of the CYP11B1 gene called a promoter region, which normally helps start the production of the 11-beta-hydroxylase enzyme, to the section of the CYP11B2 gene that provides instructions for making aldosterone synthase.

By binding to the CYP11B1 gene's promoter region, ACTH normally triggers production of the 11-beta-hydroxylase enzyme. In the fusion gene, ACTH binding abnormally triggers production of aldosterone synthase. High levels of aldosterone synthase result in excessive aldosterone production, which leads to the hypertension associated with familial hyperaldosteronism type I.

Cytogenetic Location: 8q24.3, which is the long (q) arm of chromosome 8 at position 24.3

Molecular Location: base pairs 142,872,357 to 142,879,825 on chromosome 8 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 8q24.3, which is the long (q) arm of chromosome 8 at position 24.3
  • C11B1_HUMAN
  • CPN1
  • CYP11B
  • cytochrome P-450c11
  • cytochrome P450 11B1, mitochondrial
  • cytochrome P450 11B1, mitochondrial isoform 1 precursor
  • cytochrome P450 11B1, mitochondrial isoform 2 precursor
  • cytochrome p450 XIB1
  • cytochrome P450, family 11, subfamily B, polypeptide 1
  • cytochrome P450, subfamily XIB (steroid 11-beta-hydroxylase), polypeptide 1
  • cytochrome P450C11
  • DKFZp686B05283
  • FHI
  • FLJ36771
  • P450C11
  • steroid 11-beta-hydroxylase
  • steroid 11-beta-monooxygenase