UGT1A1 Gene - UDP Glucuronosyltransferase Family 1 Member A1
Key enzyme in bilirubin metabolism and drug detoxification; associated with Gilbert and Crigler-Najjar syndromes.
Gene Information Card
| Symbol | UGT1A1 |
|---|---|
| Full Name | UDP glucuronosyltransferase family 1 member A1 |
| Gene Type | protein coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 54658 ncbi.nlm.nih.gov/gene/54658 |
| Ensembl ID | ENSG00000241370 |
| UniProt ID | P22309 |
| OMIM ID | 191740 |
| HGNC ID | 12530 |
| Aliases | UGT1A, UGT1, UDPGT, HUG-BR1, GNT1, UGT1A1*28 |
Description
The UGT1A1 gene encodes a UDP-glucuronosyltransferase enzyme, a critical phase II metabolic enzyme that catalyzes the glucuronidation of various endogenous and exogenous substrates, including bilirubin, hormones, and drugs. It is primarily expressed in the liver and is essential for the detoxification and elimination of bilirubin. Mutations in this gene can lead to inherited disorders such as Gilbert syndrome and Crigler-Najjar syndrome, and also affect drug metabolism, particularly of irinotecan and atazanavir.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gilbert syndrome | Reduced UGT1A1 enzyme activity due to promoter polymorphism (TA repeat) leading to mild unconjugated hyperbilirubinemia | OMIM 143500; ClinVar |
| Crigler-Najjar syndrome type I | Complete or near-complete absence of UGT1A1 activity due to homozygous or compound heterozygous mutations in coding region, causing severe unconjugated hyperbilirubinemia | OMIM 218800; ClinVar |
| Crigler-Najjar syndrome type II | Partial deficiency of UGT1A1 activity due to missense mutations, resulting in moderate hyperbilirubinemia | OMIM 606785; ClinVar |
| Irinotecan toxicity | UGT1A1*28 variant reduces glucuronidation of SN-38, active metabolite of irinotecan, increasing risk of severe diarrhea and neutropenia | FDA label; ClinVar |
| Neonatal hyperbilirubinemia | UGT1A1 variants, especially UGT1A1*28, contribute to prolonged jaundice in newborns | ClinVar; PMID: 23448257 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High | nTPM 100 |
| Small intestine | Medium | nTPM 20 |
| Colon | Low | nTPM 5 |
| Kidney | Low | nTPM 3 |
| Stomach | Low | nTPM 2 |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | High | Liver cancer cell line |
| Caco-2 | Medium | Colorectal adenocarcinoma |
| HEK293 | Low | Embryonic kidney |
| MCF7 | Low | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| UGT1A1*28 (TA)7 | Promoter variant | ~10-15% in Caucasians | Reduced transcription, Gilbert syndrome |
| UGT1A1*6 (G71R) | Missense | ~15-20% in East Asians | Reduced enzyme activity, Gilbert syndrome |
| c.1061C>T (P364L) | Missense | Rare | Crigler-Najjar type II |
| c.923G>A (G308E) | Missense | Rare | Crigler-Najjar type I/II |
| c.508_510del (del exon 2) | Deletion | Rare | Crigler-Najjar type I |
Mutation functional classification
Loss of Function (LOF)
Most UGT1A1 mutations, including promoter variants and missense changes, lead to reduced or absent enzyme activity, causing hyperbilirubinemia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for UGT1A1.
Dominant Negative (DN)
Not documented; UGT1A1 is a monomeric enzyme, and mutations typically act in a recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • glucuronosyltransferase activity | • bilirubin glucuronoside transport |
| • xenobiotic glucuronidation | • cellular response to drug |
| • endoplasmic reticulum membrane |
Pathways
• Bilirubin metabolism
• Drug metabolism - glucuronidation
• Porphyrin metabolism
Protein Summary
The UGT1A1 protein is a 533-amino acid transmembrane enzyme located in the endoplasmic reticulum of hepatocytes. It catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to bilirubin, making it water-soluble for excretion. It also metabolizes various drugs and endogenous compounds. The protein has a conserved UDP-glucuronosyltransferase domain and a signal peptide. Post-translational modifications include glycosylation. Structural studies show a typical GT-B fold.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UGT1A10 Knockout HEK293 Cell Line | EDJ-KQ51374 | Human | 54575 | Details Get a Quote |
| UGT1A1 Knockout HEK293 Cell Line | EDJ-KQ51384 | Human | 54658 | Details Get a Quote |
| UGT1A10 Knockout HeLa Cell Line | EDJ-KQ56441 | Human | 54575 | Details Get a Quote |
| UGT1A1 Knockout HeLa Cell Line | EDJ-KQ56454 | Human | 54658 | Details Get a Quote |
| UGT1A10 Knockout A-549 Cell Line | EDJ-KQ64935 | Human | 54575 | Details Get a Quote |
| UGT1A1 Knockout A-549 Cell Line | EDJ-KQ64947 | Human | 54658 | Details Get a Quote |
| UGT1A10 Knockout HCT 116 Cell Line | EDJ-KQ73377 | Human | 54575 | Details Get a Quote |
| UGT1A1 Knockout HCT 116 Cell Line | EDJ-KQ73390 | Human | 54658 | Details Get a Quote |
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