CYP11B2 gene

cytochrome P450 family 11 subfamily B member 2

The CYP11B2 gene provides instructions for making an enzyme called aldosterone synthase (previously known as corticosterone methyloxidase). This enzyme is found in the adrenal glands, which are located on top of the kidneys. Aldosterone synthase is a member of the cytochrome P450 family of enzymes. These enzymes are involved in the formation and breakdown of various molecules within cells.

Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body. The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone from other (precursor) molecules: the conversion of 11-deoxycorticosterone to corticosterone, the conversion of corticosterone to 18-hydroxycorticosterone, and the conversion of 18-hydroxycorticosterone to aldosterone.

At least 30 CYP11B2 gene mutations that cause corticosterone methyloxidase deficiency (also known as aldosterone synthase deficiency) have been identified. These mutations lead to insufficient production of aldosterone, which impairs the kidneys' ability to reabsorb salt (sodium chloride or NaCl) into the blood and release potassium in the urine. As a result, excessive amounts of salt in the form of charged atoms (ions) of sodium (Na+) and chlorine (Cl-) leave the body in the urine, while not enough potassium is released. The resulting imbalance of ions in the body underlies the signs and symptoms of this disorder, which include nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness.

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

By binding to the CYP11B1 gene's promoter region, a hormone called adrenocorticotropic hormone (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.

Normal variations (polymorphisms) of the CYP11B2 gene have been associated with increased risk of cardiovascular problems including hypertension, stroke caused by a lack of blood flow to the brain (ischemic stroke), and a heart rhythm abnormality called atrial fibrillation in people with heart failure. Researchers suggest that differences in blood pressure control resulting from the CYP11B2 gene variations may lead to increased risk of these cardiovascular problems.

Cytogenetic Location: 8q21-q22, which is the long (q) arm of chromosome 8 between positions 21 and 22

Molecular Location: base pairs 142,910,559 to 142,917,843 on chromosome 8 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 8q21-q22, which is the long (q) arm of chromosome 8 between positions 21 and 22
  • ALDOS
  • aldosterone synthase
  • aldosterone-synthesizing enzyme
  • C11B2_HUMAN
  • CPN2
  • CYP11B
  • CYP11BL
  • CYPXIB2
  • cytochrome P-450Aldo
  • cytochrome P-450C18
  • cytochrome P450 11B2, mitochondrial
  • cytochrome P450 11B2, mitochondrial precursor
  • cytochrome P450, family 11, subfamily B, polypeptide 2
  • cytochrome P450, subfamily XIB (steroid 11-beta-hydroxylase), polypeptide 2
  • mitochondrial cytochrome P450, family 11, subfamily B, polypeptide 2
  • P-450C18
  • P450aldo
  • P450C18
  • steroid 11-beta-monooxygenase
  • steroid 11-beta/18-hydroxylase
  • steroid 18-hydroxylase, aldosterone synthase, P450C18, P450aldo