A new blood group system, RHAG: three antigens resulting from amino acid substitutions in the Rh-associated glycoprotein

Background and Objectives Rh-associated glycoprotein (RhAG) is closely associated with the Rh proteins in the red cell membrane. Two high frequency antigens (Duclos and DSLK) and one low frequency antigen (Ol(a)) have serological characteristics suggestive of expression on RhAG. Materials and Methods RHAG was sequenced from the DNA of one Duclos-negative, one DSLK-negative, and two Ol(a+) individuals. Recombinant protein was expressed in HEK 293 cells. Protein models with RhAG subunits were constructed. Results The original Duclos-negative patient was homozygous for RHAG 316C>G, encoding Gln106Glu. HEK 293 cells expressing Gln106Glu mutant RhAG did not react with anti-Duclos. An individual with DSLK-negative red cells was homozygous for 490A>C, encoding Lys164Gln. Two Ol(a+) members of the original Norwegian family were heterozygous for 680C>T, encoding Ser227Leu. A Japanese donor with Rh-mod phenotype had Ol(a+) red cells and was homozygous for 680C>T. Conclusion The three red cell antigens encoded by RHAG form the RHAG blood group system: Duclos is RHAG1 (030001); Ol(a) is RHAG2 (030002); and DSLK is provisionally RHAG3 (030003).