CYP2D6 gene

The CYP2D6 gene (CYP2D6 stands for: Cytochrome P450 Family 2 Subfamily D Member 6 genes/pseudogenes) is a protein-coding gene located on chromosome 7q22.1.

The gene is highly polymorphic in the human population; certain alleles lead to the poor metabolizer phenotype, which is characterized by a reduced ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein because they carry two null alleles, while others lack the gene. This gene can vary in copy number, and individuals with the ultra-rapid metabolizer phenotype may have three or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Metabolic pathways associated with this gene include the clomipramine pathway, pharmacokinetics and oxidation by cytochrome P450, specifically including oxidoreductase activity and heme binding. An important paralog of this gene is CYP2J2.

Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Metabolizes the endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12- and 14,15-epoxy-eicosatrienoic acid ethanolamides (EpETrE-EAs), possibly modulating signal transduction of the endocannabinoid system.

Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol to 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a precursor of the active form all-trans-retinoic acid.

Is also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists and tricyclic antidepressants.

Diseases associated with CYP2D6 include:

• Polymorphism of the cytochrome P450-dependent monooxygenase CYP2D6. The cytochrome P450 isoenzyme 2D6 (CYP2D6) is involved in the metabolization of about 25% of the most commonly used drugs, in particular psychotropic drugs of the SSRI type (serotonin reuptake inhibitors), beta-blockers and analgesics.
• Warfarin sensitivity.

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