Defective UGT1A1 does not transfer GlcA from UDP-GlcA to BIL

Stable Identifier
Reaction [transition]
Homo sapiens
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Bilirubin (BIL) is a breakdown product of heme, causing death if allowed to accumulate in the blood. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. UGT1A1 is the only enzyme that converts bilirubin to either its monoglucuronide (BMG) or diglucuronide (BDG) conjugate. Defects in UGT1A1 can cause hyperbilirubinemia syndromes ranging from mild forms such as Gilbert syndrome (GILBS; MIM:143500) and transient familial neonatal hyperbilirubinemia (HBLRTFN; MIM:237900) to more severe Crigler-Najjar syndromes 1 and 2 (CN1, CN2; MIM:218800 and MIM:606785). Mutations causing CN1, the most severe form of hyperbilirubinemia, include Y293Mfs*69, S376F, R341*, G309E and Q357R (Ritter et al. 1992, Bosma et al. 1992, Maruo et al. 2003, Erps et al. 1994, Francoual et al. 2002).

Literature References
PubMed ID Title Journal Year
1634050 Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I

Lahiri, P, Lederstein, M, Chowdhury, NR, Chowdhury, JR, Bosma, PJ, Elferink, RP, Jansen, PL, Whitington, PF, Huang, TJ, Van Es, HH

FASEB J. 1992
1634606 Identification of a genetic alteration in the code for bilirubin UDP-glucuronosyltransferase in the UGT1 gene complex of a Crigler-Najjar type I patient

Owens, IS, Ritter, JK, Ferreira, P, Yeatman, MT

J. Clin. Invest. 1992
7906695 Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro

Hersh, JH, Owens, IS, Blossom, D, Ritter, JK, Martin, NC, Erps, LT

J. Clin. Invest. 1994
11968090 Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect related to the Q357R mutation within the UGT1 gene

Myara, A, Capel, L, Lindenbaum, A, Rivierre, A, Francoual, J, Khrouf, N, Labrune, P, Gottrand, F, Mokrani, C, Le Bihan, B

Hum. Mutat. 2002
14616765 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

Sato, H, Poon, KK, Maruo, Y, Ito, M, Mori, A, Takeuchi, Y, Takahashi, H, Iwai, M

Clin. Genet. 2003
Catalyst Activity

glucuronosyltransferase activity of UGT1A1 mutants [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of UGT1A1 mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
Crigler-Najjar syndrome DOID:3803 Bilirubin UDP glucuronyl transferase deficiency, Crigler Najjar syndrome, Crigler-Najjar syndrome (disorder), Crigler-Najjar syndrome, Crigler-Najjar syndrome, type I (disorder)
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