DurgicalDurgical
EN
Open the app

Biochemistry · Enzyme

UGT1A1 (bilirubin UDP-glucuronosyltransferase) !

Liver UGT1A1 attaches glucuronic acid to bilirubin so it dissolves in bile; its failure causes Gilbert and Crigler-Najjar.

Updated 2026-11-01

Key facts

  • Bilirubin + UDP-glucuronic acid → bilirubin monoglucuronide, then diglucuronide + UDP.
  • It is a membrane protein of the hepatocyte endoplasmic reticulum, with its active site facing the lumen.
  • It is the only enzyme that conjugates bilirubin; it also glucuronidates drugs (SN-38 of irinotecan) and estrogens.
  • The UGT1A1*28 variant (seven TA repeats in the promoter) lowers expression to about 30 % and causes Gilbert syndrome.
Also called
Bilirubin-UGT
EC number
2.4.1.17
Genes
UGT1A1

Regulation

  • It is induced by phenobarbital and other nuclear-receptor activators (CAR, PXR).
  • At birth its activity is low and it matures over the first weeks of life.

Inhibitors and toxins

  • Atazanavir and indinavir
  • Pregnanes in breast milk (proposed in breast-milk jaundice)

Clinical notes

  • Gilbert: ~30 % activity, mildly high indirect bilirubin with fasting, stress or infection; benign.
  • Crigler-Najjar type 1: no activity, risk of kernicterus; type 2: very low activity that responds to phenobarbital.
  • People with UGT1A1*28 have a higher risk of irinotecan toxicity (neutropenia, diarrhoea); genotyping can be done beforehand.

Pathways

Test yourself

Think of the answer, then tap the question to see it.

Which UGT1A1 variant most often causes Gilbert syndrome?

UGT1A1*28: seven TA repeats in the promoter that lower enzyme expression.

Which type of Crigler-Najjar responds to phenobarbital, and why?

Type 2: some enzyme remains and phenobarbital induces it; in type 1 there is no enzyme to induce.

Which anticancer drug is more toxic in people with UGT1A1*28?

Irinotecan: its active metabolite SN-38 is cleared by UGT1A1 glucuronidation.

Add to my cards (3)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: UGT1A1: UDP-glucuronosyltransferase 1A1 (human) (UniProt, 2026); UGT1A1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Gilbert syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Crigler-Najjar syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).

← All of biochemistry

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.