OMIA:001586-9685 : Deficient acetaminophen glucuronidation in Felis catus
Categories: Homeostasis / metabolism phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 606431 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2000
Molecular basis: By cloning and sequencing a very likely candidate gene (based on the observation that "The domestic cat has a significantly lower capacity to glucuronidate planar phenolic xenobiotics compared with most other mammalian species"), Court and Greenblatt (2000) showed that all cats are homozygous for a mutated form of the UGT1A6 gene that encodes UDP-glucuronosyltransferase 1A6, and hence completely lack this most important phenol-detoxification enzyme. From comparative analyses, Shrestha et al. (2011) concluded that the mutated form of the gene was fixed between 35 and 11 million years ago, resulting in all Felidae being homozygous for the mutated gene and hence the lack of the enzyme. As Shrestha et al. (2011) note, this accounts for felid's "remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment". The authors hypothesise that the loss of this gene may have been tolerated as felids became more carnivorous.
Genetic testing: Since all cats lack this gene, there is no need for any genetic testing
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|UGT1A6||UDP-glucuronosyltransferase 1A6||Felis catus||C1||NC_058375.1 (215108670..215112456)||UGT1A6||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|
|740||Deficient acetaminophen glucuronidation||UGT1A6||complex rearrangement||Naturally occurring variant||Felis_catus_9.0||C1||Felis_catus_9.0||"sequencing of the entire UGT1A6 exon 1 coding region revealed five deleterious genetic mutations ... [in cats] UGT1A6 is a pseudogene"||2000||10862526|
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.
|2011||Shrestha, B., Reed, JM., Starks, PT., Kaufman, GE., Goldstone, JV., Roelke, ME., O'Brien, SJ., Koepfli, KP., Frank, LG., Court, MH. :|
|Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory. PLoS One 6:e18046, 2011. Pubmed reference: 21464924 . DOI: 10.1371/journal.pone.0018046.|
|2000||Court, MH., Greenblatt, DJ. :|
|Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics 10:355-69, 2000. Pubmed reference: 10862526 .|
|1997||Court, MH., Greenblatt, DJ. :|
|Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochem Pharmacol 53:1041-7, 1997. Pubmed reference: 9174118 .|
|Court, MH., Greenblatt, DJ. :|
|Biochemical basis for deficient paracetamol glucuronidation in cats: an interspecies comparison of enzyme constraint in liver microsomes. J Pharm Pharmacol 49:446-9, 1997. Pubmed reference: 9232546 .|
|1984||Savides, MC., Oehme, FW., Nash, SL., Leipold, HW. :|
|The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicol Appl Pharmacol 74:26-34, 1984. Pubmed reference: 6729821 .|
|1972||Capel, ID., French, MR., Millburn, P., Smith, RL., Williams, RT. :|
|The fate of (14C)phenol in various species. Xenobiotica 2:25-34, 1972. Pubmed reference: 4211177 .|
|Davis, LE., Westfall, BA. :|
|Species differences in biotransformation and excretion of salicylate. Am J Vet Res 33:1253-62, 1972. Pubmed reference: 5022404 .|
|1958||Robinson, D., Williams, R.T. :|
|Do cats form glucuronides? Biochemical journal 68:23â€“24, 1958.|
- Created by Frank Nicholas on 21 Jul 2011
- Changed by Frank Nicholas on 17 Nov 2011
- Changed by Frank Nicholas on 09 Dec 2011
- Changed by Frank Nicholas on 17 Sep 2012