UGT1A9 (UDP glucuronosyltransferase family 1 member A9)

Gene

• Entrez ID: 54600
• Gene name: UDP glucuronosyltransferase family 1 member A9
• Gene symbol: UGT1A9
• Synonyms: HLUGP4, LUGP4, UDPGT, UDPGT 1-9, UGT-1I, UGT1-09, UGT1-9, UGT1.9, UGT1A9S, UGT1AI, UGT1I
• Chromosome: 2
• Chromosome location: 2q37.1
• Summary: 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. [provided by RefSeq, Jul 2008]

Transcription factors

Transcription factor	Regulation	Reference
HNF1A	Activation	15044625
PPARA	Activation	12582161
PPARG	Activation	12582161

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001972	Function	Retinoic acid binding	IDA	20308471
GO:0005783	Component	Endoplasmic reticulum	IDA	17179145
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006805	Process	Xenobiotic metabolic process	IDA	1910331
GO:0015020	Function	Glucuronosyltransferase activity	IDA	18052087, 20056724, 20308471, 22579593
GO:0016021	Component	Integral component of membrane	IEA
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0019899	Function	Enzyme binding	IPI	17179145
GO:0042573	Process	Retinoic acid metabolic process	IC	20308471
GO:0042803	Function	Protein homodimerization activity	IDA	17179145
GO:0051552	Process	Flavone metabolic process	IDA	18052087
GO:0052695	Process	Cellular glucuronidation	IDA	22579593
GO:0052696	Process	Flavonoid glucuronidation	IBA	21873635
GO:0052696	Process	Flavonoid glucuronidation	IDA	20056724
GO:0052697	Process	Xenobiotic glucuronidation	IBA	21873635
GO:0052697	Process	Xenobiotic glucuronidation	IDA	20056724

Other IDs

• MIM: 606434
• HGNC: 12541
• e!Ensembl: ENSG00000241119

Protein

• UniProt ID: O60656
• Protein name: UDP-glucuronosyltransferase 1A9 (UGT1A9) (EC 2.4.1.17) (UDP-glucuronosyltransferase 1-9) (UDPGT 1-9) (UGT1*9) (UGT1-09) (UGT1.9) (UDP-glucuronosyltransferase 1-I) (UGT-1I) (UGT1I) (lugP4)
• Protein function: [Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:15470161, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212). ; [Isoform 2]: Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00201	UDPGT	26 → 521	UDP-glucoronosyl and UDP-glucosyl transferase	Family

• Sequence:

  MACTGWTSPLPLCVCLLLTCGFAEAGKLLVVPMDGSHWFTMRSVVEKLILRGHEVVVVMP
  EVSWQLGRSLNCTVKTYSTSYTLEDLDREFKAFAHAQWKAQVRSIYSLLMGSYNDIFDLF
  FSNCRSLFKDKKLVEYLKESSFDAVFLDPFDNCGLIVAKYFSLPSVVFARGILCHYLEEG
  AQCPAPLSYVPRILLGFSDAMTFKERVRNHIMHLEEHLLCHRFFKNALEIASEILQTPVT
  EYDLYSHTSIWLLRTDFVLDYPKPVMPNMIFIGGINCHQGKPLPMEFEAYINASGEHGIV
  VFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGH
  PMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDL
  ENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTW
  YQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH

• Sequence length: 530

Pathways

KEGG:

Pentose and glucuronate interconversions
Ascorbate and aldarate metabolism
Steroid hormone biosynthesis
Retinol metabolism
Porphyrin metabolism
Metabolism of xenobiotics by cytochrome P450
Drug metabolism - cytochrome P450
Drug metabolism - other enzymes
Metabolic pathways
Biosynthesis of cofactors
Bile secretion
Chemical carcinogenesis - DNA adducts
Chemical carcinogenesis - receptor activation

Reactome:

Glucuronidation
PPARA activates gene expression

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Sickle Cell	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505	22558097
Breast cancer	Malignant neoplasm of breast	rs587776547, rs1137887, rs137853007, rs587776650, rs80359351, rs80359714, rs121917783, rs104886456, rs121964878, rs80359874, rs80357868, rs80357508, rs387906843, rs80357569, rs80358158, rs80357524, rs80357115, rs80357945, rs80357729, rs80357609, rs80357259, rs80357981, rs80358063, rs80357389, rs80356862, rs80359876, rs80357580, rs80358053, rs80358089, rs80187739, rs397507241, rs80358069, rs80357590, rs80357284, rs80357941, rs80359261, rs80359272, rs80359276, rs276174813, rs80358474, rs80359316, rs1555282969, rs80359388, rs80359499, rs80359505, rs80359520, rs80359526, rs80359533, rs56253082, rs80358824, rs80359554, rs80359636, rs80359651, rs80359659, rs80359011, rs80359012, rs80359013, rs80359718, rs397507410, rs81002812, rs80359730, rs80359152, rs80359159, rs397507419, rs28897759, rs80359211, rs80359775, rs397514577, rs397507584, rs80358435, rs80358456, rs80359340, rs80359343, rs80359365, rs80358579, rs397507670, rs80358593, rs80359406, rs80359444, rs80359454, rs276174853, rs276174854, rs80359483, rs80359537, rs80358815, rs80358843, rs80359558, rs80359560, rs80359594, rs80358893, rs28897743, rs397507900, rs397507906, rs397507918, rs80358971, rs80358981, rs397507941, rs80359030, rs80359035, rs41293511, rs397507396, rs81002806, rs80359112, rs397508006, rs81002893, rs45580035, rs80359760, rs397508051, rs80359772, rs4987049, rs80359777, rs80357770, rs397508867, rs62625303, rs397508874, rs80357506, rs80357287, rs273898674, rs80358042, rs80358083, rs80357058, rs41286296, rs80357960, rs80356945, rs80357223, rs386134270, rs80358116, rs80357856, rs80357424, rs397509050, rs80357485, rs80357966, rs397509067, rs80357310, rs80356866, rs80357260, rs80357437, rs80358023, rs80358086, rs80357133, rs80356993, rs80357997, rs80357239, rs80357227, rs397509243, rs80356969, rs80356959, rs63750617, rs63751319, rs587779315, rs200640585, rs398122546, rs80357543, rs398122687, rs80359328, rs398122779, rs398122783, rs62517194, rs80358029, rs515726060, rs180177103, rs180177111, rs180177133, rs587776527, rs180177135, rs180177136, rs515726117, rs587779813, rs587779909, rs587780024, rs587780100, rs28909982, rs121908698, rs180177100, rs-1, rs587780210, rs587780240, rs587780639, rs587781269, rs587781353, rs587781471, rs587781658, rs587781697, rs587781730, rs587781894, rs587781948, rs587782005, rs587782011, rs200928781, rs587781558, rs370228071, rs587782245, rs587782401, rs180177110, rs587782504, rs72552322, rs587782531, rs587782620, rs587782680, rs587782774, rs587782818, rs730881411, rs730881389, rs564652222, rs397507768, rs587776419, rs730881868, rs730881940, rs56383036, rs758972589, rs201089102, rs730881348, rs786202608, rs786201886, rs786203318, rs786203775, rs786203714, rs786202033, rs750621215, rs786203884, rs786203650, rs772821016, rs863224521, rs864622223, rs864622655, rs375699023, rs876659572, rs768362387, rs876659535, rs876658957, rs483353072, rs876659435, rs267608041, rs876661113, rs730881369, rs878853535, rs772228129, rs878855122, rs760551339, rs80359596, rs397509222, rs886039630, rs886039683, rs886040828, rs587781799, rs886040374, rs886040649, rs397507967, rs878854957, rs886040043, rs1057517589, rs1060502769, rs866380588, rs863224765, rs1064793243, rs747563556, rs1555074976, rs1064795885, rs753961188, rs1064794708, rs869312772, rs1064793887, rs1131690820, rs1135401928, rs1135401868, rs1135401859, rs1553370324, rs397507630, rs1555283160, rs1555283251, rs1555283262, rs1555283361, rs1555286298, rs1555288462, rs886040950, rs1555289566, rs776323117, rs80357123, rs1555579627, rs1555580697, rs80358054, rs1555593302, rs1328985852, rs763470424, rs1555139694, rs878854697, rs1555461217, rs1555461765, rs774684620, rs766416564, rs1554558613, rs1305740166, rs1555461460, rs1555461407, rs1555461586, rs1555567202, rs1555607022, rs1555069815, rs1442299125, rs1474786480, rs1555084947, rs1555457867, rs141087784, rs1482641121, rs1564830522, rs1565469955, rs1565503137, rs864622613, rs755263466, rs757679199, rs1593903166, rs1597801649, rs1603293306, rs879253880, rs80358754, rs1597062038, rs45494092, rs1603275367, rs887358871, rs1597091518, rs1966967065, rs1064793049, rs2082872908, rs2085078278, rs2072475243
Obesity	Obesity	rs34911341, rs74315349, rs1474810899, rs121918111, rs796065034, rs753856820, rs796065035, rs121918112, rs-1, rs104894023, rs137852821, rs1580764441, rs137852822, rs137852823, rs137852824, rs13447324, rs121913562, rs121913564, rs74315393, rs121913556, rs2989924, rs193922650, rs193922685, rs193922687, rs751160202, rs1421085, rs747681609, rs1553400259, rs13447339, rs370479598, rs1554394014, rs1553174844, rs756232889, rs369841551, rs1557670950, rs1571321748, rs148538980, rs1572820988, rs1591461970, rs1419374563, rs745921568, rs144159890, rs1570714352, rs779783209, rs1573250294, rs1573254045, rs1580744791, rs1580746829, rs6548238, rs7138803, rs7754840	25246029
Crigler-najjar syndrome	Crigler Najjar syndrome, type 1, Crigler Najjar syndrome, type 2	rs587776761, rs72551353, rs111033539, rs72551349, rs72551348, rs587776762, rs62625011, rs281865418, rs587776763, rs587776764, rs587776765, rs587776766, rs34993780, rs72551351, rs-1, rs111033541, rs797046091, rs748219743, rs72551340, rs1553620849, rs766536479, rs72551343, rs139607673	11182932, 26697581, 15712364
Gilbert disease	Gilbert Disease (disorder)	rs72551349, rs62625011, rs34993780, rs72551351, rs748219743
Lucey-driscoll syndrome	Lucey-Driscoll syndrome (disorder)	rs34993780, rs3755319
Cholelithiasis	Cholelithiasis	rs121918440, rs72552778, rs387906528, rs759202962, rs377160065, rs1051861187, rs757693457, rs752563752	22558097
Metabolic syndrome	Metabolic Syndrome X	rs367643250, rs587777380, rs777736953	30621171

Unknown
Disease name	Disease term	dbSNP ID	References
Kidney failure	Kidney Failure, Acute		20623750
Acute kidney insufficiency	Acute Kidney Insufficiency		20623750