OMIA:001405-9615 : Metabolizer of a cognitive enhancer in Canis lupus familiaris
Categories: Homeostasis / metabolism phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 124060 (gene)
Links to MONDO diseases: No links.
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.
|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_051834.1 (38023809..38029593)||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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|274||Beagle||Metabolizer of a cognitive enhancer||CYP1A2||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||30||g.37821686C>T||c.1117C>T||p.(R373*)||rs852922442||rs852922442||2004||15564884||Variant coordinates obtained from or confirmed by EBI's Variant 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., 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.|
|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.|
|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.|
- 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