UDP-glucuronosyltransferase 1A1
Function
Isoform 1
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558).
Isoform 2
Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.
Involvement in disease
Gilbert syndrome
GILBS
Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
None
The disease is caused by variants affecting the gene represented in this entry.
Transient familial neonatal hyperbilirubinemia
HBLRTFN
A condition characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants.
None
The disease may be caused by variants affecting the gene represented in this entry. The defect has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unclear. Defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. Mutations are identical to those detected in patients with Gilbert syndrome, a risk factor of neonatal non-physiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia.
Crigler-Najjar syndrome 1
CN1
Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Crigler-Najjar syndrome 2
CN2
Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the UDP-glycosyltransferase family.
Tissue Specificity
Isoform 1
Expressed in liver, colon and small intestine. Not expressed in kidney, esophagus and skin.
Isoform 2
Expressed in liver, colon, small intestine and kidney. Not expressed in esophagus and skin.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Cytoplasm
- Perinuclear region
Alternative names
GNT1, UGT1, UGT1A1, UDP-glucuronosyltransferase 1A1, Bilirubin-specific UDPGT isozyme 1, UDP-glucuronosyltransferase 1-1, UDP-glucuronosyltransferase 1A isoform 1, hUG-BR1, UDPGT 1-1, UGT1*1, UGT1-01, UGT1.1