UGT1A3

UGT1A3 is a human gene that encodes the enzyme UDP-glucuronosyltransferase 1A3, a member of the UDP-glucuronosyltransferase (UGT) family involved in phase II drug metabolism. The enzyme catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to a broad range of endogenous and exogenous substrates, increasing their water solubility and facilitating renal or biliary excretion. UGT1A3 is primarily expressed in the liver but is also found in extrahepatic tissues such as the intestine, contributing to local glucuronidation of xenobiotics and endogenous compounds.

The UGT1A3 gene lies in the UGT1A gene cluster on chromosome 2q37, a region that contains multiple related genes. This cluster uses an unusual gene structure in which several first exons (exon 1A variants) can be paired with shared downstream exons to produce different isoforms through alternative splicing. This arrangement allows tissue- and substrate-specific patterns of expression and activity among the UGT1A family.

Substrate specificity for UGT1A3 includes a variety of phenolic and amine-containing compounds, with activity that often overlaps with other UGT1A enzymes. Its contribution to bilirubin glucuronidation is considered secondary to the principal bilirubin enzyme UGT1A1, but UGT1A3 can participate in glucuronidation of certain drugs and endogenous molecules that are less efficiently processed by UGT1A1.

Genetic variation in UGT1A3 includes multiple polymorphisms that can alter enzyme activity in a substrate-dependent manner. These variants can influence individual differences in drug metabolism and detoxification, though the clinical relevance is context-dependent and subject to ongoing research.