UGT1A3: UDP Glucuronosyltransferase Family 1 Member A3
Genetic and functional insights into UGT1A3, a key phase II drug-metabolizing enzyme involved in bilirubin and xenobiotic glucuronidation.
Gene Information Card
| Symbol | UGT1A3 |
|---|---|
| Full Name | UDP Glucuronosyltransferase Family 1 Member A3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 54659 ncbi.nlm.nih.gov/gene/54659 |
| Ensembl ID | ENSG00000241635 |
| UniProt ID | P22309 |
| OMIM ID | 606429 |
| HGNC ID | 12537 |
| Aliases | UGT1A, UGT1A3, UDPGT, UGT1-03, UGT1A3*1, UGT1A3*2 |
Description
UGT1A3 encodes a UDP-glucuronosyltransferase enzyme (EC 2.4.1.17) that catalyzes the glucuronidation of bilirubin, steroid hormones, and numerous xenobiotics. It is part of the UGT1A gene complex on chromosome 2q37.1, which produces multiple isoforms through alternative splicing. UGT1A3 is primarily expressed in the liver and gastrointestinal tract and plays a critical role in phase II drug metabolism and detoxification.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gilbert syndrome | Reduced bilirubin glucuronidation due to UGT1A1 promoter variants; UGT1A3 variants may modify phenotype | PMID: 10677221 |
| Crigler-Najjar syndrome | Severe UGT1A1 deficiency; UGT1A3 polymorphisms can influence residual activity | PMID: 10677221 |
| Drug-induced liver injury | Altered glucuronidation capacity from UGT1A3 variants may increase hepatotoxin exposure | PMID: 19085932 |
| Colorectal cancer | UGT1A3 polymorphisms associated with altered irinotecan metabolism and toxicity | PMID: 19085932 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 8.3 | Medium |
| Colon | 6.1 | Medium |
| Kidney | 3.2 | Low |
| Stomach | 2.8 | Low |
| Pancreas | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| Caco-2 | 9.8 | Colorectal adenocarcinoma cell line |
| LS180 | 7.4 | Colorectal adenocarcinoma cell line |
| HEK293 | 0.5 | Embryonic kidney cell line (low expression) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | 0.02 | Loss of start codon, reduced protein expression |
| c.211G>A (p.Ala71Thr) | missense | 0.05 | Reduced enzyme activity |
| c.440C>T (p.Thr147Ile) | missense | 0.03 | Altered substrate specificity |
| c.763G>A (p.Gly255Arg) | missense | 0.01 | Decreased glucuronidation activity |
Mutation functional classification
Loss of Function (LOF)
UGT1A3 variants such as p.Ala71Thr and p.Gly255Arg reduce enzyme activity and glucuronidation capacity.
Gain of Function (GOF)
No well-characterized gain-of-function variants reported for UGT1A3.
Dominant Negative (DN)
No evidence of dominant-negative effects for UGT1A3 mutations.
View complete mutation data：
Gene Ontology (GO)
| • metabolic process (GO:0008152) | • glucuronosyltransferase activity (GO:0015020) |
| • endoplasmic reticulum (GO:0005783) | • plasma membrane (GO:0005886) |
| • bilirubin glucuronidation (GO:0052695) |
Pathways
• Bilirubin metabolism (Reactome: R-HSA-189483)
• Glucuronidation (Reactome: R-HSA-156588)
• Phase II conjugation (KEGG: map00982)
Protein Summary
UGT1A3 is a 533-amino acid transmembrane protein localized to the endoplasmic reticulum. It catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to a variety of substrates, including bilirubin, estrogens, and drugs such as irinotecan. The enzyme exhibits broad substrate specificity and is a key determinant of drug clearance and toxicity. Polymorphisms in UGT1A3 contribute to interindividual variability in drug response and susceptibility to hyperbilirubinemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UGT1A3 Knockout HEK293 Cell Line | EDJ-KQ51385 | Human | 54659 | Details Get a Quote |
| UGT1A3 Knockout HeLa Cell Line | EDJ-KQ56455 | Human | 54659 | Details Get a Quote |
| UGT1A3 Knockout A-549 Cell Line | EDJ-KQ64948 | Human | 54659 | Details Get a Quote |
| UGT1A3 Knockout HCT 116 Cell Line | EDJ-KQ73391 | Human | 54659 | Details Get a Quote |
