Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system

Mattias Möller, Yan Quan Lee, Karina Vidovic, Sven Kjellström, Linda Björkman, Jill R. Storry and Martin L. Olsson

Key points

  • Expression of the Xg blood group protein is governed by rs311103 and its minor allele disrupts a GATA motif to cause the Xg(a-) phenotype.

  • These data elucidate the genetic basis of the last unresolved blood group system and make genotyping for Xga status possible.


The Xga blood group is differentially expressed on erythrocytes from males and females. The underlying gene, PBDX, was identified already in 1994 but the molecular background for Xga expression remains undefined. This gene, now designated XG, partly resides in the pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xga allele frequencies in different populations to 2,612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution. The same SNP had the most significant impact on XG transcript levels in whole blood (P=2.0×10-22). The minor allele, rs311103C, disrupts a GATA-binding motif 3.7 kb upstream of the transcription start point. This silences erythroid XG-mRNA expression and causes the Xg(a–) phenotype, a finding corroborated by SNP genotyping in 119 blood donors. Binding of GATA1 to biotinylated oligonucleotide probes with rs311103G but not rs311103C was observed by EMSA and proven by mass spectrometry. Finally, a luciferase reporter assay indicated this GATA motif to be active for rs311103G but not rs311103C in HEL cells. By using an integrated bioinformatics and molecular biology approach, we elucidated the underlying genetic basis for the last unresolved blood group system and made Xga genotyping possible.

  • Submitted March 30, 2018.
  • Accepted May 7, 2018.