Meyahealth
Home
ENES
HomeGeneticsGeneUGT1A1 gene
Back to Gene

UGT1A1 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

UGT1A1 gene

The UGT1A1 gene provides instructions for making an enzyme essential for processing bilirubin, a substance produced when red blood cells break down.

Normal Function

The UGT1A1 gene belongs to a family of genes that provide instructions for making enzymes called UDP-glucuronosyltransferases. These enzymes perform a chemical reaction called glucuronidation, in which a compound called glucuronic acid is attached to various substances.

The protein produced from the UGT1A1 gene, called the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme, is the only enzyme that glucuronidates bilirubin. This enzyme converts the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic form (conjugated bilirubin), allowing it to be dissolved and removed from the body. The bilirubin-UGT enzyme is primarily found in liver cells, where conjugated bilirubin is dissolved in bile and excreted with solid waste.

Health Conditions Related to Genetic Changes

Crigler-Najjar syndrome

At least 85 mutations in the UGT1A1 gene are associated with Crigler-Najjar syndrome, which occurs when both copies of the gene are altered. This condition is characterized by high levels of unconjugated bilirubin in the blood (unconjugated hyperbilirubinemia) and yellowing of the skin and eyes (jaundice).

  • Crigler-Najjar syndrome type 1 (CN1): Individuals have no enzyme function, leading to severe symptoms.
  • Crigler-Najjar syndrome type 2 (CN2): Individuals have less than 20 percent of normal enzyme function.
  • Kernicterus: A form of brain damage caused by the accumulation of unconjugated bilirubin in the brain, which can be lethal.

Gilbert syndrome

Gilbert syndrome is characterized by periods of mild unconjugated hyperbilirubinemia. It occurs when both copies of the UGT1A1 gene are altered, resulting in approximately 30 percent of normal enzyme function.

  • UGT1A1*28: The most common genetic change in many populations, involving an extra TA nucleotide pair in the promoter region, which impairs protein production.
  • Gly71Arg (G71R): A common missense mutation in Asian populations that results in reduced enzyme function.

Other disorders

  • Transient familial neonatal hyperbilirubinemia: Mutations in the UGT1A1 gene increase the risk of severe jaundice in newborns, which usually resolves in 1 to 2 weeks.
  • Breast milk jaundice: A condition where unconjugated bilirubin levels increase during breastfeeding. It is thought that a substance in breast milk may trigger bilirubin buildup in infants who already have impaired bilirubin-UGT enzyme function due to a UGT1A1 gene mutation.

Frequently Asked Questions

Diagnosis typically involves blood tests to measure bilirubin levels (total, unconjugated, and conjugated) and liver function. Genetic testing can then confirm a UGT1A1 gene mutation. The specific mutation and its effect on enzyme function (e.g., complete absence in Crigler-Najjar type 1, reduced function in type 2 or Gilbert syndrome) will determine the severity of the condition and guide management strategies.
For individuals with Gilbert syndrome, managing bilirubin levels often involves avoiding triggers like prolonged fasting, dehydration, excessive alcohol consumption, and stress. Maintaining a regular eating schedule, staying well-hydrated, and getting adequate rest can help. For Crigler-Najjar syndrome, lifestyle changes alone are insufficient, and medical treatments like phototherapy or liver transplantation are necessary.
Crigler-Najjar syndrome is much more severe than Gilbert syndrome. Crigler-Najjar type 1 involves a complete or near-complete lack of the bilirubin-UGT enzyme, leading to very high and dangerous levels of unconjugated bilirubin, severe jaundice, and a high risk of brain damage (kernicterus). Type 2 is less severe, with some enzyme function (less than 20%). Gilbert syndrome is a mild condition where the enzyme has about 30% of normal function, resulting in intermittent, mild jaundice, often triggered by stress, illness, or fasting, but generally without serious health consequences.
The primary warning sign of high bilirubin is jaundice, a yellowing of the skin and eyes. In severe cases, especially with Crigler-Najjar syndrome, dangerously high levels can lead to symptoms of kernicterus, such as lethargy, poor feeding, high-pitched crying, arching of the back, and seizures. Emergency medical attention is crucial if jaundice is severe, rapidly worsening, or accompanied by any neurological symptoms, as prompt treatment is needed to prevent brain damage.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.