UGT1A9: UDP Glucuronosyltransferase Family 1 Member A9
Phase II drug metabolism and bilirubin conjugation gene
Gene Information Card
| Symbol | UGT1A9 |
|---|---|
| Full Name | UDP Glucuronosyltransferase Family 1 Member A9 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 54600 ncbi.nlm.nih.gov/gene/54600 |
| Ensembl ID | ENSG00000242247 |
| UniProt ID | O60656 |
| OMIM ID | 606434 |
| HGNC ID | 12539 |
| Aliases | UDPGT, UGT1A9, UGT1-9, UGT1.9, UGT1A9S |
Description
UGT1A9 encodes a UDP-glucuronosyltransferase enzyme that catalyzes the glucuronidation of small lipophilic substrates, including bilirubin, hormones, drugs, and xenobiotics. This enzyme is a member of the UGT1 family and is primarily expressed in the liver and kidney. Genetic variants in UGT1A9 can alter drug metabolism and are associated with altered pharmacokinetics of drugs such as mycophenolic acid and irinotecan.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gilbert syndrome (modifier) | Reduced UGT1A9 activity may contribute to mild unconjugated hyperbilirubinemia in combination with UGT1A1 variants. | ClinVar, OMIM |
| Drug-induced toxicity (irinotecan, mycophenolate) | UGT1A9 polymorphisms reduce glucuronidation capacity, leading to increased drug exposure and toxicity. | ClinVar, PubMed |
| Hyperbilirubinemia, familial | UGT1A9 variants may exacerbate bilirubin accumulation when UGT1A1 is deficient. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Small intestine | 4.1 | Low |
| Colon | 2.9 | Low |
| Stomach | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Liver cancer cell line, high expression |
| HEK293 | 0.5 | Low endogenous expression |
| Caco-2 | 3.1 | Colorectal adenocarcinoma, moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.98C>T (p.Thr33Ile) | missense | 0.5% (global) | Reduced enzyme activity |
| c.440C>T (p.Pro147Leu) | missense | 0.2% | Decreased glucuronidation |
| c.726T>G (p.Tyr242*) | nonsense | <0.1% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense variants (e.g., p.Tyr242*, p.Thr33Ile) reduce or abolish glucuronidation activity.
Gain of Function (GOF)
No common gain-of-function variants reported.
Dominant Negative (DN)
Not described for UGT1A9.
View complete mutation data：
Gene Ontology (GO)
| • glucuronosyltransferase activity (GO:0015020) | • UDP-glucuronate metabolic process (GO:0052692) |
| • endoplasmic reticulum (GO:0005783) | • xenobiotic metabolic process (GO:0006805) |
| • metal ion binding (GO:0046872) |
Pathways
• Bilirubin conjugation (Reactome: R-HSA-156588)
• Glucuronidation (Reactome: R-HSA-156588)
• Irinotecan metabolism (PharmGKB: PA166104994)
Protein Summary
UGT1A9 is a 529-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, steroids, and drugs. The enzyme is critical for the elimination of many therapeutic agents and endogenous compounds. Polymorphisms in UGT1A9 contribute to interindividual variability in drug response and toxicity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UGT1A9 Knockout HEK293 Cell Line | EDJ-KQ51380 | Human | 54600 | Details Get a Quote |
| UGT1A9 Knockout HeLa Cell Line | EDJ-KQ56449 | Human | 54600 | Details Get a Quote |
| UGT1A9 Knockout A-549 Cell Line | EDJ-KQ64943 | Human | 54600 | Details Get a Quote |
| UGT1A9 Knockout HCT 116 Cell Line | EDJ-KQ73385 | Human | 54600 | Details Get a Quote |
