ABCMdb

PMID: 10053008

Toh S, Wada M, Uchiumi T, Inokuchi A, Makino Y, Horie Y, Adachi Y, Sakisaka S, Kuwano M
Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.
Am J Hum Genet. 1999 Mar;64(3):739-46., [PubMed]

Sentences

No. Mutations Sentence Comment

25 ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Arg768Trp ABCC2 p.Gln1382Arg We previously had isolated the human MRP2/cMOAT gene as the candidate transporter for the glucuronide- Table 1 Mutations in MRP2/cMOAT and Serum Total- and Direct-Bilirubin and Urinary Coproporphyrine Isomer I Fractions, in Patients with DJS and in Their Families PEDIGREE AND PATIENT/ FAMILY MEMBER ALTERATION IN cMAOT EXON PUTATIVE CONSEQUENCE CONCENTRATION [NORMAL RANGE]a T-bilirubin [.3-1.0] (mg/dl) D-bilirubin [.1-.6] (mg/dl) Urinary Coproporphyrin I Fraction [!27]b (%) 1: DJ1 2302(CrT)/2302(CrT) 18 R768W/R768W 5.0 3.8 NT 2: DJ2 2302(CrT)/wild type 18 R768W/wild type NT NT 42.1 DJ3 2439ϩ2(TrC)/wild type 18 Splice donor/wild type NT NT 43.5 DJ4 2302(CrT)/2439ϩ2(TrC) 18 R768W/splice donor 1.3 .8 94.5 DJ5 2302(CrT)/2439ϩ2(TrC) 18 R768W/splice donor 1.3 .8 93.6 DJ6 Wild type/wild type ) Wild type/wild type NT NT NT 3: DJ7 1815ϩ2(TrA)/1815ϩ2(TrA) 13 Splice donor/splice donor 5.2 3.8 NT 4: DJ8 2302(CrT)/2302(CrT) 18 R768W/R768W 4.8 3.2 NT 5: DJ9 2439ϩ2(TrC)/4145(ArG) 18/29 Splice donor/Q1382R 2.5 1.6 80.0 6: DJ10 2439ϩ2(TrC)/2439ϩ2(TrC) 18 Splice donor/splice donor 2.1 1.6 85.7 DJ11 2439ϩ2(TrC)/wild type 18 Splice donor/wild type .9 .4 48.0 DJ12 2439ϩ2(TrC)/wild type 18 Splice donor/wild type .5 .2 36.9 a NT ϭ not tested. Login to comment 76 ABCC2 p.Arg768Trp This alteration was accompanied by an amino acid substitution, R768W, in the active transporter-family signature (Higgins 1992) (fig. 1). Login to comment 84 ABCC2 p.Gln1382Arg The third alteration resulted in amino acid substitution Q1382R in the position at the ABC region. Login to comment 99 ABCC2 p.Arg768Trp The first mutation, identified in DJ8 in the present study, is 2302(CrT) and is associated with the amino acid change Arg768 rTrp (R768W) in the highly conserved domain, the Walker C motif. Login to comment 104 ABCC2 p.Gln1382Arg The third mutation is 4145(ArG), which predicts amino acid change Gln1382 rArg (Q1382R) within the ABC at the carboxyl-terminal end. Login to comment 123 ABCC2 p.Arg768Trp This mutation is accompanied by an amino acid substitution, R768W, in the Walker C motif, which is a highly conserved domain among the ABC-transporter family. Login to comment