In other species: domestic cat , pig , sheep

Categories: Homeostasis / metabolism phene

Mendelian trait/disorder: unknown

Disease-related: unknown

Species-specific description: Martinez et al. (2024): "Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds."

Molecular basis: Martinez et al. (2020) investigatd suspected CYP2B11 deficiency in Greyhounds: "Greyhound livers metabolized CYP2B11 substrates slower, possessed lower CYP2B11 protein abundance, but had similar or higher mRNA expression than other breeds. Gene resequencing identified three CYP2B11 haplotypes, H1 (reference), H2, and H3 that were differentiated by mutations in the gene 3'-untranslated region (3'-UTR). ... Greyhounds had the highest CYP2B11-H3 allele frequency, while CYP2B11-H2 was widely distributed across most breeds. Using 3'-UTR luciferase reporter constructs, CYP2B11-H3 showed markedly lower gene expression (over 70%) compared to CYP2B11-H1 while CYP2B11-H2 expression was intermediate. Truncated mRNA transcripts were observed in CYP2B11-H2 and CYP2B11-H3 but not CYP2B11-H1 transfected cells. Our results implicate CYP2B11 3'-UTR mutations as a cause of decreased CYP2B11 enzyme expression in Greyhounds through reduced translational efficiency."
Martinez et al. (2024) identified two POR protein variants (Glu315Gln and Asp570Glu). Their "results indicate that the Glu315Gln mutation ... reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings."

Breed: Greyhound (Dog) (VBO_0200638).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated genes: