A SLC14A1 c.230G>A variant causes loss of Kidd antigen expression

Background The Kidd (Jk) blood group system is defined by the Jk a , Jk b and Jk3 antigens encoded by the SLC14A1 gene. The Jk(a-b-) phenotype, characterized by the absence of these antigens, is a rare blood group phenotype with a low population frequency, and its molecular basis is primarily associated with variants in the SLC14A1 gene. Herein, we identified an individual with the Jk(a-b-) phenotype carrying a variant, and evaluated whether this variant affects Jk antigen expression. Methods The Jk(a-b-) phenotype was identified by conventional serological typing. The coding sequence of the SLC14A1 gene was analyzed using polymerase chain reaction sequence-based typing (PCR-SBT), and haplotype analysis was performed using single-molecule sequencing. The functional impact of the variant was evaluated through in vitro transfection and expression assays, and Jk b antigen expression on transfected cells was assessed by flow cytometry. The potential functional impact of the variant was also evaluated using in silico prediction tools. Results Jk a , Jk b and Jk3 antigens were absent in the proband. PCR-SBT identified three heterozygous single-nucleotide variants (SNVs) and two homozygous SNVs across four exons of the SLC14A1 gene. Single-molecule sequencing revealed two haplotypes: one comprising c.342-1G>A, c.588A>G, and c.838G>A, and the other comprising c.230G>A, c.499A>G, c.588A>G, and c.838G>A. In silico analysis predicted c.230G>A to be a deleterious variant and indicated that it altered interactions with neighboring atoms. Functional assays showed that cells transfected with JK(c.230G>A+c.499A>G+c.588A>G+c.838G>A) did not express the Jk b antigen, while cells transfected with the JK*02 allele or JK(c.499A>G+c.588A>G+c.838G>A) exhibited high levels of Jk b antigen expression. Conclusions A JK null allele and its critical SNV were identified, and the functional effect of the variant was confirmed through transfection and expression studies.