ABCMdb

PMID: 22246507

Zelinski T, Coghlan G, Liu XQ, Reid ME
ABCG2 null alleles define the Jr(a-) blood group phenotype.
Nat Genet. 2012 Jan 15;44(2):131-2. doi: 10.1038/ng.1075., [PubMed]

Sentences

No. Mutations Sentence Comment

26 ABCG2 p.Val12Met ABCG2 p.Val12Met The third ABCG2 null genotype consists of a compound molecular background, with one allele giving rise to a p.Val12Met substitution coupled with a premature stop codon at amino acid 236 and a second allele encoding the p.Val12Met substitution coupled with the normal Arg236 amino acid. Login to comment 37 ABCG2 p.Val12Met ABCG2 p.Val12Met In studies with polarized LLC-PK1 cells (renal epithelial cells derived from porcine kidneys), cells expressing ABCG2 V12M were ten times more sensitive to topoisomerase inhibitor I than cells transfected with control vectors8, and in vesicles expressing the V12M variant, substrate efflux was also reduced compared with that in control cells transfected with control vectors. Login to comment 38 ABCG2 p.Val12Met Further, analysis of ABCG2 V12M localization by immunofluorescence showed that ABCG2 was not present at the apical membrane8. Login to comment 39 ABCG2 p.Val12Met In contrast, a previous study did not observe a decrease in urate transport nor a significant difference in the amount of protein in immunoblots of lysates from HEK293 cells expressing the V12M variant5. Login to comment 40 ABCG2 p.Val12Met Further investigation of the subject in our study who was homozygous for the mutation encoding p.Val12Met and heterozygous for the one encoding p.Arg236* might have resolved this issue, but, unfortunately, this individual was not available for follow-up studies. Login to comment 42 ABCG2 p.Val12Met This finding is not surprising, as the p.Val12Met substitution falls in a region likely to encode a signal peptide. Login to comment 43 ABCG2 p.Val12Met Alternatively, it is possible that the p.Val12Met substitution alters the Jra antigenic epitope within the transmembrane domain (amino acids 390-655) of ABCG2. Login to comment 121 ABCG2 p.Val12Met Table 1 Nucleotide and predicted protein changes in ABCG2 in six Jr(a-) subjects Subject Ancestrya Nucleotide Protein 1 Caucasian c.736C>T p.Arg246* 2 Caucasian c.736C>T p.Arg246* 3 Asian c.376C>T p.Gln126* 4 Asian c.376C>T p.Gln126* 5 Asian c.376C>T p.Gln126* 6 Asian c.34G>A c.706C>T p.Val12Met p.Arg236* All samples were used with permission under protocols approved by the New York Blood Center and the University of Manitoba`s Health Research Ethics Board. Login to comment