ABCMdb

PMID: 9806540

Strautnieks SS, Bull LN, Knisely AS, Kocoshis SA, Dahl N, Arnell H, Sokal E, Dahan K, Childs S, Ling V, Tanner MS, Kagalwalla AF, Nemeth A, Pawlowska J, Baker A, Mieli-Vergani G, Freimer NB, Gardiner RM, Thompson RJ
A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.
Nat Genet. 1998 Nov;20(3):233-8., [PubMed]

Sentences

No. Mutations Sentence Comment

100 ABCB11 p.Arg575* A Belgian (B2) family and a Latin American (Q) family carry the 1723 C→T (R575X) mutation. Login to comment 101 ABCB11 p.Arg1057* A second Belgian family (B5) carries the 3169 C→T (R1057X) mutation, and a Polish family (57) carries 908delG, which deletes one base of codon 303, causing a frameshift. Login to comment 105 ABCB11 p.Glu297Gly 890 A→G (E297G) predicts the substitution of a glutamate by a glycine in the second intracellular loop, between transmembrane spans 4 and 5. Login to comment 110 ABCB11 p.Lys461Glu The mutation 1381 A→G (K461E) predicts the substitution of a glutamate for a lysine in the first Walker A motif, and is present in one Greek family in which the parents are fourth cousins. Login to comment 111 ABCB11 p.Asp482Gly One Polish family and one Austrian family carry 1445 A→G (D482G), which causes substitution of a glycine for an aspartate. Login to comment 121 ABCB11 p.Gly982Arg One Saudi Arabian family carries 2944 G→A (G982R), which is predicted to replace a glycine with an arginine, thereby disrupting transmembrane span 11. Login to comment 122 ABCB11 p.Arg1268Gln ABCB11 p.Arg1153Cys The mutation 3457 C→T (R1153C) is present in a further two Saudi Arabian families and replaces a conserved arginine with a cysteine in the second nucleotide binding fold. One family of Kuwaiti origin carries 3803 G→A (R1268Q), which predicts replacement of arginine with glutamine in the second nucleotide binding fold. One or more of these mutations have been found in 25 PFIC families. Login to comment 142 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly ABCB11 p.Arg1268Gln ABCB11 p.Arg1153Cys ABCB11 p.Gly982Arg ABCB11 p.Arg575* ABCB11 p.Lys461Glu ABCB11 p.Arg1057* The ABC transporter family of proteins is the largest so far iden- Table 1• BSEP mutations found in PFIC patients Nucleotide mutation Amino acid number/ Protein consequence Families mutation 1723 C→T R575X Termination codon in first B2 heterozygous nucleotide binding fold Q homozygous 3169 C→T R1057X Termination codon in second B5 heterozygous nucleotide binding fold 908 del G 303 17 novel amino acids then truncation Family 57 heterozygous 3767-3768 ins C 1256 39 novel amino acids then truncation Family 99 homozygous 890 A→G E297G Glutamate to glycine in the intracellular loop S1, S3, S4B, S5, S6, S7, 38 homozygous between transmembrane spans 4 and 5 S4A, B5, B6, B7, 53, L heterozygous 1381 A→G K461E Lysine to glutamate in first Walker A motif Family 55 homozygous 1445 A→G D482G Aspartate to glycine in first P and 52 homozygous nucleotide binding fold 2944 G→A G982R Glycine to arginine in transmembrane span 11 Family 18 homozygous 3457 C→T R1153C Arginine to cysteine in second C and D homozygous nucleotide binding fold 3803 G→A R1268Q Arginine to glutamine in second J homozygous nucleotide binding fold In each case the nucleotide position in the human coding sequence is given along with details of the predicted protein consequence. Login to comment 144 ABCB11 p.Glu297Gly Fig. 5 The amino acid sequence in the immediate vicinity of the E297G mutation. Login to comment 159 ABCB11 p.Arg575* The mutation R575X is the result of a C→T transition in a CpG dinucleotide (1723 C→T). Login to comment 162 ABCB11 p.Asp482Gly Although no ancestral link can be established, 1445 A→G (D482G) has been found in both a Polish family and an Austrian family. Login to comment 163 ABCB11 p.Arg1153Cys Two consanguineous families of Saudi Arabian Bedouin origin which are not known to be related, but share the same family name, carry 3457 C→T (R1153C). Login to comment 164 ABCB11 p.Glu297Gly The mutation 890 A→G (E297G) has been found in 13 families. Login to comment 236 ABCB11 p.Asp482Gly ABCB11 p.Glu297Gly ABCB11 p.Arg1268Gln ABCB11 p.Arg1153Cys ABCB11 p.Gly982Arg ABCB11 p.Lys461Glu The endonucleases used were: HphI (E297G), BpmI (K461E), FokI (D482G), AlwNI (G982R), BsrBI (R1153C) and AvaII (R1268Q). Login to comment