UGT1A9
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Gene ontology | |||
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| Location (UCSC) | Chr 2: 233.67 – 233.77 Mb | Chr 1: 87.98 – 88.15 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene.[5][6][7][8]
Function
This gene encodes a
lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5′ exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols.[8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Irinotecan Pathway edit
- ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".
Medicinal Chemistry Case Studies
During hit optimization of HSD17B13 inhibitors significant glucuronidation of the phenol moiety was observed in vitro and in vivo.[9] UGT phenotyping revealed UGT1A9 as main contributor for glucuronidation. In addition, tissue distribution as well as bile excretion studies were performed.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000241119 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000090165 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1910331.
- PMID 9295054.
- PMID 1339448.
- ^ a b "Entrez Gene: UGT1A9 UDP glucuronosyltransferase 1 family, polypeptide A9".
- PMID 36727857.
Further reading
- Innocenti F, Kroetz DL, Schuetz E, et al. (2009). "Comprehensive Pharmacogenetic Analysis of Irinotecan Neutropenia and Pharmacokinetics". J. Clin. Oncol. 27 (16): 2604–14. PMID 19349540.
- Holmes MV, Shah T, Vickery C, et al. (2009). Luo Y (ed.). "Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies". PLOS ONE. 4 (12): e7960. PMID 19956635.
- Prausa SE, Fukuda T, Maseck D, et al. (2009). "UGT genotype may contribute to adverse events following medication with mycophenolate mofetil in pediatric kidney transplant recipients". Clin. Pharmacol. Ther. 85 (5): 495–500. S2CID 33309241.
- Ross CJ, Katzov-Eckert H, Dubé MP, et al. (2009). "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy". Nat. Genet. 41 (12): 1345–9. S2CID 21293339.
- Korprasertthaworn P, Udomuksorn W, Yoovathaworn K (2009). "Three novel single nucleotide polymorphisms of UGT1A9 in a Thai population". Drug Metab. Pharmacokinet. 24 (5): 482–5. PMID 19881262.
- Nakajima M, Koga T, Sakai H, et al. (2010). "N-Glycosylation plays a role in protein folding of human UGT1A9". Biochem. Pharmacol. 79 (8): 1165–72. S2CID 11013645.
- van Schaik RH, van Agteren M, de Fijter JW, et al. (2009). "UGT1A9 -275T>A/-2152C>T polymorphisms correlate with low MPA exposure and acute rejection in MMF/tacrolimus-treated kidney transplant patients". Clin. Pharmacol. Ther. 86 (3): 319–27. S2CID 21082902.
- Sanna S, Busonero F, Maschio A, et al. (2009). "Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia". Hum. Mol. Genet. 18 (14): 2711–8. PMID 19419973.
- King CD, Rios GR, Green MD, Tephly TR (2000). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. PMID 11465080.
- Sánchez-Fructuoso AI, Maestro ML, Calvo N, et al. (2009). "The prevalence of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T and its influence on mycophenolic acid pharmacokinetics in stable renal transplant patients". Transplant. Proc. 41 (6): 2313–6. PMID 19715905.
- Chu XY, Liang Y, Cai X, et al. (2009). "Metabolism and renal elimination of gaboxadol in humans: role of UDP-glucuronosyltransferases and transporters". Pharm. Res. 26 (2): 459–68. S2CID 24490597.
- Bock KW, Gschaidmeier H, Heel H, et al. (1999). "Functions and transcriptional regulation of PAH-inducible human UDP-glucuronosyltransferases". Drug Metab. Rev. 31 (2): 411–22. PMID 10335444.
- Saito Y, Sai K, Maekawa K, et al. (2009). "Close association of UGT1A9 IVS1+399C>T with UGT1A1*28, *6, or *60 haplotype and its apparent influence on 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation in Japanese". Drug Metab. Dispos. 37 (2): 272–6. S2CID 2886803.
- Tukey RH, Strassburg CP (2000). "Human UDP-glucuronosyltransferases: metabolism, expression, and disease". Annu. Rev. Pharmacol. Toxicol. 40: 581–616. PMID 10836148.
- Ménard V, Girard H, Harvey M, et al. (2009). "Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population". Hum. Mutat. 30 (4): 677–87. S2CID 6235077.
- Cecchin E, Innocenti F, D'Andrea M, et al. (2009). "Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan". J. Clin. Oncol. 27 (15): 2457–65. PMID 19364970.
- Fujiwara R, Nakajima M, Yamamoto T, et al. (2009). "In silico and in vitro approaches to elucidate the thermal stability of human UDP-glucuronosyltransferase (UGT) 1A9". Drug Metab. Pharmacokinet. 24 (3): 235–44. PMID 19571435.
- Kadakol A, Ghosh SS, Sappal BS, et al. (2000). "Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype". Hum. Mutat. 16 (4): 297–306. S2CID 24275067.
- Johnson AD, Kavousi M, Smith AV, et al. (2009). "Genome-wide association meta-analysis for total serum bilirubin levels". Hum. Mol. Genet. 18 (14): 2700–10. PMID 19414484.
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