UGT1A8: UDP Glucuronosyltransferase Family 1 Member A8
Genetic and functional insights into UGT1A8, a key phase II drug-metabolizing enzyme involved in bilirubin and xenobiotic glucuronidation.
Gene Information Card
| Symbol | UGT1A8 |
|---|---|
| Full Name | UDP Glucuronosyltransferase Family 1 Member A8 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 54576 ncbi.nlm.nih.gov/gene/54576 |
| Ensembl ID | ENSG00000242247 |
| UniProt ID | Q9HAW9 |
| OMIM ID | 606432 |
| HGNC ID | 12538 |
| Aliases | UGT1-08, UGT1.8, UDPGT 1-8, UGT1A8S |
Description
UGT1A8 encodes a UDP-glucuronosyltransferase enzyme that catalyzes the glucuronidation of bilirubin, steroids, and numerous xenobiotics. It is part of the UGT1A gene complex on chromosome 2q37.1 and is primarily expressed in the gastrointestinal tract. Genetic variants in UGT1A8 can alter drug metabolism and are associated with altered risk for certain cancers and hyperbilirubinemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperbilirubinemia, familial | Reduced bilirubin glucuronidation due to UGT1A8 deficiency | OMIM #606432 |
| Colorectal cancer | UGT1A8 polymorphisms may alter detoxification of carcinogens | PMID: 19033658 |
| Irinotecan toxicity | Reduced glucuronidation of SN-38 active metabolite | ClinVar: rs1042597 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.5 | High |
| Small intestine | 8.3 | Medium |
| Liver | 1.2 | Low |
| Kidney | 0.5 | Not detected |
| Stomach | 6.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 15.2 | Colorectal adenocarcinoma cell line |
| HT-29 | 10.8 | Colorectal adenocarcinoma cell line |
| HepG2 | 0.9 | Hepatocellular carcinoma cell line |
| LS180 | 18.4 | Colorectal adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1042597 (c.518C>G, p.Ala173Gly) | missense | 0.28 (global) | Reduced glucuronidation activity toward SN-38 |
| rs17863762 (c.830G>A, p.Arg277His) | missense | 0.02 (global) | Decreased enzyme activity |
| rs4148323 (c.211G>A, p.Gly71Arg) | missense | 0.15 (East Asian) | Reduced bilirubin glucuronidation |
Mutation functional classification
Loss of Function (LOF)
rs17863762 (Arg277His) reduces catalytic activity by >50%.
Gain of Function (GOF)
No confirmed gain-of-function variants reported.
Dominant Negative (DN)
Not described for UGT1A8.
View complete mutation data：
Gene Ontology (GO)
| • metabolic process (GO:0008152) | • glucuronosyltransferase activity (GO:0015020) |
| • endoplasmic reticulum (GO:0005783) | • flavonoid glucuronidation (GO:0052696) |
| • cellular response to xenobiotic stimulus (GO:0042403) |
Pathways
• Bilirubin metabolism (Reactome: R-HSA-189483)
• Glucuronidation (Reactome: R-HSA-156588)
• Irinotecan pharmacokinetics (PharmGKB: PA166104994)
Protein Summary
UGT1A8 is a 530-amino acid transmembrane protein localized to the endoplasmic reticulum. It conjugates glucuronic acid to lipophilic substrates, enhancing their water solubility for excretion. The enzyme is critical for bilirubin clearance and detoxification of drugs like irinotecan. Structural variations in the substrate-binding domain affect substrate specificity and catalytic efficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UGT1A8 Knockout HEK293 Cell Line | EDJ-KQ51375 | Human | 54576 | Details Get a Quote |
| UGT1A8 Knockout HeLa Cell Line | EDJ-KQ56442 | Human | 54576 | Details Get a Quote |
| UGT1A8 Knockout A-549 Cell Line | EDJ-KQ64936 | Human | 54576 | Details Get a Quote |
| UGT1A8 Knockout HCT 116 Cell Line | EDJ-KQ73378 | Human | 54576 | Details Get a Quote |
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