This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small 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.[4]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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. doi:10.1038/clpt.2009.3. PMID19225446.
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. doi:10.1038/ng.478. PMID19898482.
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. doi:10.2133/dmpk.24.482. PMID19881262.
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. doi:10.1016/j.bcp.2009.11.020. PMID19951703.
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. doi:10.1038/clpt.2009.83. PMID19494809.
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. doi:10.1016/j.transproceed.2009.06.038. PMID19715905.
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. doi:10.1007/s11095-008-9799-5. PMID19082692.
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. doi:10.1081/DMR-100101927. PMID10335444.
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. doi:10.1124/dmd.108.024208. PMID18981166.
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. doi:10.1002/humu.20946. PMID19204906.
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. doi:10.1200/JCO.2008.19.0314. PMID19364970.
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. doi:10.2133/dmpk.24.235. PMID19571435.
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. doi:10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z. PMID11013440.