Aberrant intracellular trafficking of a variant B glycosyltransferase

Transfusion. 2008 Sep;48(9):1898-905. doi: 10.1111/j.1537-2995.2008.01782.x. Epub 2008 May 29.


Background: Little is known about the mechanism by which amino acid polymorphisms outside the catalytically active cleft of ABO glycosyltransferases cause weak ABO phenotypes.

Study design and methods: Extensive ABO phenotyping and genotyping were performed to classify the blood of a healthy blood group O donor with weak isoagglutinins. ABO antigen and glycosyltransferase expression profiles were then studied in eukaryotic transfection experiments, and the topology of ABO glycosyltransferase was analyzed.

Results: The donor's red blood cells were retyped as A(weak), and his serum contained weakly reactive anti-A and anti-B. Sequence analysis revealed two novel ABO alleles. A donor splice-site mutation detected at the exon 6/intron 6 junction of an ABO*A101 allele was predicted to result in skipping exon 6 in the mRNA. The other haplotype displayed a single 688G>C substitution predicting a Gly230Arg exchange in the catalytic domain in an otherwise normal ABO*B101 allele. The transfection studies revealed very weak expression of B antigen by the novel ABO*B allele. According to the topologic analysis, steric hindrance due to the Gly230Arg exchange may cause conformational changes in the variant B transferase. Compared to the wild-type B transferase, the transfected cells exhibited lower-level protein expression and intracellular dislocation.

Conclusion: This study provides first evidence that aberrant trafficking of variant ABO transferases may be involved in the formation of weak ABO phenotypes.

MeSH terms

  • ABO Blood-Group System / genetics
  • ABO Blood-Group System / immunology
  • Alleles
  • Cell Line, Tumor
  • Flow Cytometry
  • Genotype
  • Glycosyltransferases / genetics*
  • Glycosyltransferases / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Space / metabolism
  • Microscopy, Fluorescence
  • Mutation
  • Polymorphism, Genetic*
  • Protein Transport
  • Transfection


  • ABO Blood-Group System
  • Glycosyltransferases