Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome.
Members of the ATP-binding cassette (ABC) transporter superfamily are mutated to cause diseases that include cystic fibrosis, hyperinsulinemia, adrenoleukodystrophy, Stargardt disease and multidrug resistance. We recently isolated a novel human member of ABC transporter superfamily as the candidate transporter for the glucuronide and glutathione-conjugated antitumor agents, and found it highly homologous to the rat cmoat gene. consistent with recent findings of defects in the homologous cmoat gene in two rat models of hyperbilirubinemia (TR- and Eisai), we report two deletions and a missense mutation in the active transport family signature region in the gene in patients with hyperbilirubinemia II/Dubin-Johnson syndrome (DJS; MIM 237500), respectively. These results strongly implicate the cMOAT gene as responsible for the defects in DJS patients.
Wada
M
M
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka 812-82, Japan. wada@biochem1.med.kyushu-u.ac.jp
Toh
S
S
Taniguchi
K
K
Nakamura
T
T
Uchiumi
T
T
Kohno
K
K
Yoshida
I
I
Kimura
A
A
Sakisaka
S
S
Adachi
Y
Y
Kuwano
M
M
D000595:Amino Acid Sequence; D027321:Anion Transport Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D007566:Jaundice, Chronic Idiopathic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D017384:Sequence Deletion
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary