UGT1A9

UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene.

Function
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5′ exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols.

Medicinal Chemistry Case Studies
During hit optimization of HSD17B13 inhibitors significant glucuronidation of the phenol moiety was observed in vitro and in vivo. UGT phenotyping revealed UGT1A9 as main contributor for glucuronidation. In addition, tissue distribution as well as bile excretion studies were performed.