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UDP-glucuronosyltransferases

The UGT1A gene encodes the enzyme UDP-glucuronosyltransferases which is involved in bilirubin metabolism. Mutations cause various forms of hyperbilirubinemia in which unconjugated bilirubin is elevated in serum. Inheritance may be dominant or recessive.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Crigler-Najjar syndrome 1
UGT1A
Crigler-Najjar syndrome 2
UGT1A
Gilbert syndrome
UGT1A
Familial transient neonatal hyperbilirubinemia
UGT1A

References:

1.

Girard H et al. (2007) Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity.

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2.

Harding D et al. (1988) Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells.

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3.

Nagai F et al. (1988) Studies on the genetic linkage of bilirubin and androsterone UDP-glucuronyltransferases by cross-breeding of two mutant rat strains.

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4.

Jackson MR et al. (1987) Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA.

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5.

Zahreddine HA et al. (2014) The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation.

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6.

Lee JS et al. (2011) Genetic variation in UGT1A1 typical of Gilbert syndrome is associated with unconjugated hyperbilirubinemia in patients receiving tocilizumab.

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7.

Harding D et al. (1990) Chromosomal mapping of a human phenol UDP-glucuronosyltransferase, GNT1.

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8.

Wooster R et al. (1991) Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.

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9.

Burchell B et al. (1991) The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence.

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10.

Ritter JK et al. (1991) Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells.

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11.

Nguyen N et al. (2008) Disruption of the ugt1 locus in mice resembles human Crigler-Najjar type I disease.

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12.

Peters WH et al. (1984) The molecular weights of UDP-glucuronyltransferase determined with radiation-inactivation analysis. A molecular model of bilirubin UDP-glucuronyltransferase.

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13.

Udomuksorn W et al. (2007) Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates.

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14.

None (1990) The cDNA sequence and expression of a variant 17 beta-hydroxysteroid UDP-glucuronosyltransferase.

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15.

Miles JS et al. (1991) Mapping genes encoding drug-metabolizing enzymes in recombinant inbred mice.

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16.

Bosma PJ et al. (1992) Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I.

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17.

Mackenzie PI et al. (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily.

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18.

Edison ES et al. (2005) Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism.

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19.

French D et al. (2005) Global gene expression as a function of germline genetic variation.

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20.

Petit FM et al. (2005) Paternal isodisomy for chromosome 2 as the cause of Crigler-Najjar type I syndrome.

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21.

Kaniwa N et al. (2005) Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C> T (P229L) found in an African-American.

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22.

Maruo Y et al. (2004) Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome.

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23.

Strassburg CP et al. (1997) Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue.

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24.

Akaba K et al. (1999) Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese.

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25.

Akaba K et al. (1998) Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.

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26.

Beutler E et al. (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism?

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27.

Gantla S et al. (1998) Splice-site mutations: a novel genetic mechanism of Crigler-Najjar syndrome type 1.

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28.

Iyer L et al. (1998) Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.

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29.

Iolascon A et al. (1998) UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary spherocytosis.

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30.

Sampietro M et al. (1997) The expression of uridine diphosphate glucuronosyltransferase gene is a major determinant of bilirubin level in heterozygous beta-thalassaemia and in glucose-6-phosphate dehydrogenase deficiency.

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31.

Galanello R et al. (1997) Hyperbilirubinaemia in heterozygous beta-thalassaemia is related to co-inherited Gilbert's syndrome.

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32.

Kaplan M et al. (1997) Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.

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33.

Mackenzie PI et al. (1997) The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence.

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34.

Ritter JK et al. (1992) Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient.

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35.

Rosatelli MC et al. (1997) Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome type I.

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36.

Mojarrabi B et al. (1996) cDNA cloning and characterization of the human UDP glucuronosyltransferase, UGT1A3.

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37.

Seppen J et al. (1996) A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II.

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38.

Bosma PJ et al. (1993) A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II.

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39.

van Es HH et al. (1993) Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37.

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40.

Ritter JK et al. (1993) A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase.

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41.

Moghrabi N et al. (1993) Cosegregation of intragenic markers with a novel mutation that causes Crigler-Najjar syndrome type I: implication in carrier detection and prenatal diagnosis.

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42.

Aono S et al. (1994) A new type of defect in the gene for bilirubin uridine 5'-diphosphate-glucuronosyltransferase in a patient with Crigler-Najjar syndrome type I.

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43.

Erps LT et al. (1994) Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro.

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44.

Borlak J et al. (2000) Molecular diagnosis of a familial nonhemolytic hyperbilirubinemia (Gilbert's syndrome) in healthy subjects.

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45.

Sato H et al. (2013) Association of breast-fed neonatal hyperbilirubinemia with UGT1A1 polymorphisms: 211G>A (G71R) mutation becomes a risk factor under inadequate feeding.

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46.

Maruo Y et al. (2000) Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene.

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47.

Johnson AD et al. (2009) Genome-wide association meta-analysis for total serum bilirubin levels.

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48.

Lin R et al. (2009) Association of polymorphisms in four bilirubin metabolism genes with serum bilirubin in three Asian populations.

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49.

Lin JP et al. (2003) Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: a genomewide scan in the Framingham study.

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50.

Koiwai O et al. (1995) Gilbert's syndrome is caused by a heterozygous missense mutation in the gene for bilirubin UDP-glucuronosyltransferase.

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51.

Bosma PJ et al. (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome.

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52.

None (2008) Pharmacogenetics of Gilbert's syndrome.

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53.

Hsieh TY et al. (2007) Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter.

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54.

Sugatani J et al. (2002) Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia.

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55.

Moghrabi N et al. (1992) Chromosomal assignment of human phenol and bilirubin UDP-glucuronosyltransferase genes (UGT1A-subfamily).

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56.

Maruo Y et al. (1999) A case of anorexia nervosa with hyperbilirubinaemia in a patient homozygous for a mutation in the bilirubin UDP-glucuronosyltransferase gene.

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57.

Suhre K et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research.

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58.

Yamamoto K et al. (1998) Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II.

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59.

Seppen J et al. (1994) Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

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60.

Petit F et al. (2006) Crigler-Najjar type II syndrome may result from several types and combinations of mutations in the UGT1A1 gene.

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61.

Kadakol A et al. (2001) Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus.

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62.

Moghrabi N et al. (1993) Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2.

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63.

Gollan JL et al. (1975) Prolonged survival in three brothers with severe type 2 Crigler-Najjar syndrome. Ultrastructural and metabolic studies.

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64.

Jansen PL et al. (1992) New developments in glucuronidation research: report of a workshop on "glucuronidation, its role in health and disease".

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65.

Kren BT et al. (1999) Correction of the UDP-glucuronosyltransferase gene defect in the gunn rat model of crigler-najjar syndrome type I with a chimeric oligonucleotide.

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66.

None (2004) Pharmacogenetics and drug development: the path to safer and more effective drugs.

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67.

Innocenti F et al. (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan.

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68.

Maruo Y et al. (2003) Co-occurrence of three different mutations in the bilirubin UDP-glucuronosyltransferase gene in a Chinese family with Crigler-Najjar syndrome type I and Gilbert's syndrome.

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69.

Basu NK et al. (2004) Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake.

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70.

Ohnishi A et al. (2003) Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II.

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71.

Sato H et al. (1992) Mapping of the mouse bilirubin UDP-glucuronosyltransferase gene (Gnt-1) to chromosome 1 by restriction fragment length variations.

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72.

Ritter JK et al. (1992) A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini.

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73.

Fertrin KY et al. (2003) UDP-glucuronosyltransferase 1 gene promoter polymorphism is associated with increased serum bilirubin levels and cholecystectomy in patients with sickle cell anemia.

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74.

Premawardhena A et al. () The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications.

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75.

Labrune P et al. (2002) Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome.

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76.

Francoual J et al. (2002) Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect related to the Q357R mutation within the UGT1 gene.

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77.

King CD et al. (2000) UDP-glucuronosyltransferases.

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78.

Gong QH et al. (2001) Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.

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79.

Premawardhena A et al. (2001) Genetic determinants of jaundice and gallstones in haemoglobin E beta thalassaemia.

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80.

Kadakol A et al. (2000) Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.

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81.

Kaplan M et al. (2000) Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates.

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82.

Findlay KA et al. (2000) Characterization of the uridine diphosphate-glucuronosyltransferase-catalyzing thyroid hormone glucuronidation in man.

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83.

Tukey RH et al. (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease.

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84.

Kimura T et al. (1999) Intermittent jaundice in patients with acute leukaemia: a common mutation of the bilirubin uridine-diphosphate glucuronosyltransferase gene among Asians.

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85.

Monaghan G et al. (1999) Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

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86.

NCBI article

NCBI 7361 external link
87.

OMIM.ORG article

Omim 191740 external link
88.

Orphanet article

Orphanet ID 120380 external link
Update: Aug. 14, 2020
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