OMIA 001405-9615 : Metabolizer of a cognitive enhancer in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 124060

Mendelian trait/disorder: yes

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2004

Species-specific name: Protein deletion

Species-specific description: In the first of two papers, Mise et al. (2004; Drug Metab Dispos 32:240-5) reported a polymorphism in ability to metabolize a novel cognitive enhancer AC-3933. Tenmizu et al. (2004) reported a similar polymorphism for a novel and selective phosphodiesterase type 4 inhibitor, YM-64227. In both cases, dogs were classified as poor metabolizers (PM) or extensive metabolizers (EM).

Molecular basis: By cloning and sequencing a set of likely candidate genes (based on knowledge of the physiology of this type of metabolism) Mise et al. (2004; Pharmacogenetics 14:769-73) showed that a 1117C>T nonsense mutation in the CYP1A2 gene is associated with the poor metabolizer (PM) phenotype in relation to AC-3933. The same mutation was reported by Tenmizu et al. (2004) as being associated with the PM phenotype in relation to YM-64227.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CYP1A2 cytochrome P450, family 1, subfamily A, polypeptide 2 Canis lupus familiaris 30 NC_006612.3 (37818400..37824192) CYP1A2 Homologene, Ensembl, NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Beagle Metabolizer of a cognitive enhancer CYP1A2 nonsense (stop-gain) CanFam3.1 30 g.37821686 c.1117C>T p. R373* rs852922442 2004 15564884 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2006 Tenmizu, D., Noguchi, K., Kamimura, H. :
Elucidation of the effects of the CYP1A2 deficiency polymorphism in the metabolism of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1h)-one (YM-64227), a phosphodiesterase type 4 inhibitor, and its metabolites in dogs. Drug Metab Dispos 34:1811-6, 2006. Pubmed reference: 16882764. DOI: 10.1124/dmd.106.011213.
Tenmizu, D., Noguchi, K., Kamimura, H., Ohtani, H., Sawada, Y. :
The canine CYP1A2 deficiency polymorphism dramatically affects the pharmacokinetics of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-D]-pyrimidine-2-(1H)-one (YM-64227), a phosphodiesterase type 4 inhibitor. Drug Metab Dispos 34:800-6, 2006. Pubmed reference: 16473917. DOI: 10.1124/dmd.105.008722.
2004 Mise, M., Hashizume, T., Matsumoto, S., Terauchi, Y., Fujii, T. :
Identification of non-functional allelic variant of CYP1A2 in dogs. Pharmacogenetics 14:769-73, 2004. Pubmed reference: 15564884.
Mise, M., Yadera, S., Matsuda, M., Hashizume, T., Matsumoto, S., Terauchi, Y., Fujii, T. :
Polymorphic expression of CYP1A2 leading to interindividual variability in metabolism of a novel benzodiazepine receptor partial inverse agonist in dogs. Drug Metab Dispos 32:240-5, 2004. Pubmed reference: 14744947. DOI: 10.1124/dmd.32.2.240.
Tenmizu, D., Endo, Y., Noguchi, K., Kamimura, H. :
Identification of the novel canine CYP1A2 1117 C > T SNP causing protein deletion. Xenobiotica 34:835-46, 2004. Pubmed reference: 15742977. DOI: 10.1080/00498250412331285436.

Edit History

  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 Sep 2012