ABCMdb

ABCB4 p.Ile764Leu

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Publications

PMID: 17264802 [PubMed] Lang C et al: "Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury."

No. Sentence Comment

5 Results Four highly conserved nonsynonymous mutations were specific for drug-induced liver injury [ABCB11: D676Y (drug-induced cholestasis) and G855R (drug-induced cholestasis); ABCB4: I764L (drug-induced cholestasis) and L1082Q (drug-induced hepatocellular injury)]. Login to comment
142 With the exception of the I764L, which was located in the eighth transmembrane domain of MDR3, all other nonsynonymous variants were Table 6 ABCB4 (MDR3)1 variant sites in drug-induced liver injury Amplicon DNA position cDNA position Nucleotide reference Nucleotide variant AA change AF DC (n = 46) AF DH (n = 26) AF controls (n = 112) Amplicon - 3 Intron - 4 - 394 T G 0.02 0.00 0.05 Amplicon - 3 Intron - 4 - 197 G T 0.00 0.04 0.00 Amplicon - 3 Exon - 3 - 410 T C Noncoding 0.02 0.00 0.05 Amplicon - 2 Exon - 2 - 228 C T Noncoding 0.04 0.08 0.11 Amplicon - 1 Intron - 2 - 221 C T 0.04 0.08 0.11 Amplicon - 1 Intron - 2 - 204 A G 0.04 0.08 0.13 Amplicon 1 Intron - 1 - 301 C G 0.07 0.08 0.17 Amplicon 1 Intron - 1 - 220 C T 0.02 0.00 0.05 Amplicon 1 Intron - 1 - 201 C G 0.04 0.08 0.13 Amplicon 1 Intron - 1 - 184 T C 0.33 0.46 0.26 Amplicon 4 Exon 4 175 C T syn 0.05 0.08 0.13 Amplicon 5 Intron 4 - 61 C T 0.11 0.08 0.03 Amplicon 5 Intron 5 113 A G 0.07 0.08 0.16 Amplicon 6 Intron 5 - 62 AGAAA delAGAAA 0.05 0.04 0.08 Amplicon 6 Intron 5 - 50 GAAA delGAAA 0.02 0.00 0.00 Amplicon 6 Exon 6 504 C T syn 0.62 0.46 0.57 Amplicon 6 Exon 6 523 A G T175A_c 0.02 0.00 0.03 Amplicon 8 Exon 8 711 A T syn 0.07 0.08 0.15 Amplicon 11 Intron10 - 43 T C 0.02 0.00 0.00 Amplicon 12 Intron 11 - 88 T delT 0.05 0.00 0.07 Amplicon 12 Intron 11 - 81 T delT 0.04 0.04 0.00 Amplicon 12 Exon 12 1314 G A syn 0.00 0.04 0.00 Amplicon 12 Intron 12 130 G T 0.08 0.04 0.06 Amplicon 13 Intron 12 - 40 G A 0.02 0.00 0.05 Amplicon 15 Intron 14 - 39 A G 0.02 0.08 0.01 Amplicon 15 Exon 15 1769 G A R590Q_c 0.02 0.00 0.01 Amplicon 16 Exon 16 1954 A G R652G 0.09 0.04 0.07 Amplicon 16 Intron 16 55 A G 0.09 0.04 0.05 Amplicon 17 Intron 17 16 T C 0.03 0.00 0.05 Amplicon 18 Exon 18 2290 A C I764L_c 0.02 0.00 0.00 Amplicon 20 Intron 20 40 A G 0.11 0.00 0.06 Amplicon 23 Intron 23 70 G T 0.00 0.04 0.00 Amplicon 25 Exon 25 3245 T A L1082Q_c 0.00 0.04 0.00 Amplicon 27 Intron 26 - 16 T C 0.35 0.58 0.92 Amplicon 28 Intron 27 - 72 T C 0.11 0.00 0.07 cDNA numbers are relative to the ATG site and based on the cDNA sequence from GenBank accession number NM_000443.2. Login to comment
150 Six variant sites were specific for patients with drug-induced liver injury, including three intronic and three coding region changes (synonymous: exon 12: 1314G > A; nonsynonymous: exon 18: 2290A > C-I764L and exon 25: 3245T > A-L1082Q). Login to comment
151 The heterozygous I764L mutation was observed in a patient with DC taking risperidone (no. Login to comment
163 The estimated IC50 was 50 and 60 mmol/l for reference BSEP Fig. 4 Extracellular I764L T175A R652G R590Q Cytoplasm L1082Q Secondary structure of multidrug resistance protein 3 (MDR3) with nonsynonymous coding region variants. Login to comment
200 The conserved I764L site encountered in a heterozygous patient with risperidone-induced cholestasis was located in the transmembrane domain of MDR3, a region that exhibits only very little variation in members of the ABC superfamily of transporters [29]. Login to comment

PMID: 20422497 [PubMed] Pauli-Magnus C et al: "Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy."

No. Sentence Comment

125 Specifically, full-length sequencing of ABCB11 and ABCB4 revealed a heterozygous p.D676Y mutation in BSEP observed in a patient taking fluvas- tatin and a heterozygous p.I764L mutation in MDR3 observed in a patient taking risperidone:115 both suffered from hepatocellular cholestasis. Login to comment
127 In the case of BSEP, in vitro taurocholate transport was unchanged for the mutated protein whereas the impact of the p.I764L mutation on MDR3 expression and function was not investigated. Login to comment

PMID: 18004213 [PubMed] Alfirevic A et al: "Tacrine-induced liver damage: an analysis of 19 candidate genes."

No. Sentence Comment

196 Two ABCB4 nonsynonymous SNPs (I764L and L1082Q) were specific for drug-induced cholestasis and hepatocellular injury, respectively. Login to comment