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 engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Genetic testing: Since all cats lack this gene, there is no need for any genetic testing

Associated gene: