Defective UGT1A4 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 and 4 are the only enzymes that transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugate. Defects in UGT1A4 can cause hyperbilirubinemia syndromes ranging from mild forms such as Gilbert syndrome (GILBS; MIM:143500) to the more severe Crigler-Najjar syndromes 1 and 2 (CN1, CN2; MIM:218800 and MIM:606785). A mutation causing the severest form, CN1, is S376F (Bosma et al. 1992).

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
Catalyst Activity

glucuronosyltransferase activity of UGT1A4 S376F [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of UGT1A4 S376F [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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