Structure-function relationship of FCGR2/3 genetic variants. (A) Schematic representation of the FCRG2/3 locus and the relative location of 9 SNPs and haplotypes. (B) Schematic gene structure of FCGR2C and associated SNPs in the 3 FCGR2C alleles. In whites, FCGR2C-STOP is the most common allele and is not expressed due to a premature stop codon in exon 3. In some individuals, a SNP in exon 3 leads to an open reading frame, resulting in the expression of the FcγRIIc protein. In the study by Meinderts et al, 9 out of 272 patients with SCD carried this allele, which is also referred to as the classical FCGR2C-ORF. The nonclassical FCGR2C.nc-ORF allele differs from the classical haplotype by an additional splice site mutation near exon 7 that leads to a stop codon and thus no protein expression. The FCGR2C.nc-ORF haplotype is associated with a decreased risk of alloimmunization in patients with SCD. IgG, immunoglobulin G; ORF, open reading frame. Illustration by Julia Bonnell, New York Blood Center. The figure has been adapted from Figures 2 and 3 in the article by Meinderts et al that begins on page 2121.