CYP2A6: genetics, structure, regulation, and function

Drug Metabol Drug Interact. 2012 May 5;27(2):73-88. doi: 10.1515/dmdi-2012-0001.


The human CYP2A gene subfamily consists of three members, CYP2A6, CYP2A7, and CYP2A13. The CYP2A6 gene is highly polymorphic with approximately 40 annotated allelic variants. Individuals homozygous for some of these alleles have a total lack of CYP2A6 activity. The CYP2A6 protein is most abundant in liver and is expressed, although at much lower levels, in some other tissues, especially nasal mucosa. CYP2A6 differs from other human liver CYP forms in that it participates in the metabolism of very few currently used drugs. The two most relevant substrates for CYP2A6 are coumarin and nicotine. Coumarin is the marker substance for determining CYP2A6 activity both in vitro and in vivo. Approximately 80% of a nicotine dose is eliminated by CYP2A6, and there is a clear link between CYP2A6 genotypes, smoking behavior, and lung cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Coumarins / adverse effects
  • Coumarins / metabolism
  • Cytochrome P-450 CYP2A6
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Mice
  • Models, Molecular
  • Multigene Family
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Nicotine / metabolism
  • Nicotinic Agonists / metabolism
  • Polymorphism, Genetic
  • Smoking / metabolism
  • Substrate Specificity


  • Coumarins
  • Enzyme Inhibitors
  • Nicotinic Agonists
  • Nicotine
  • coumarin
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6