(P-IG-29) JK*B allele with c.510del (p.Lys170fs) associated with null phenotype and anti-Jk3

Background/Case Studies: The antigens of the Kidd blood group system, including antithetical antigens Jka and Jkb, are encoded by JK*A and JK*B alleles of the SLC14A1 gene, respectively. The gene is rich in genetic variation in many ethic groups. There are currently 23 null JK*A alleles and 22 null JK*B alleles assigned and curated by the ISBT working party on Red Cell Immunogenetics and Blood Group Terminology. Here we present a novel JK*B null allele found in a blood donor of Asian descent with anti-Jk3.

Study

Design/Methods: The blood donor RBCs were typed using standard agglutination methods. Molecular testing was performed using HEA BeadChip (Immucor). Sanger sequencing of SLC14A1 exons 3, 5 and 6 was performed, and results were aligned to the reference sequence using Sequencher software (GeneCodes).

Results/Findings: The donor RBCs typed Jk(a-b-). HEA BeadChip testing predicted the donor to type Jk(a-b+). Sequencing of exon 6 of SLC14A1 and alignment to the reference sequence found the sample to be homozygous for a single nucleotide deletion at c.510 as well as for the common synonymous SNV c.588A>G. The deletion is predicted to result in a frameshift and production of a truncated protein missing more than 100 amino acids including several transmembrane regions. This variant is not listed on the ISBT 009 JK blood group allele table (v8.0).

Conclusions: The donor was homozygous for c.510del (p.Lys170fs). This variant is listed in ClinVar (SCV002498596.1) with “uncertain clinical significance”. The report of this blood donor that types Jk(a-b-) and has anti-Jk3 supports the interpretation that this allele is associated with a null phenotype. The variant has an allele frequency of 0.0033% in the study-wide ExAc database and 0.016% in the Asian ExAc cohort. We propose this allele be assigned JK*02N.23.

Importance of research: it is important to continue to add to the catalogue of known alleles of blood group antigen genes, especially those that impact phenotype. This abstract describes the twenty-third null JK*B allele. In addition, characterizing variant and null alleles can aid in better understanding the biochemical function of the SLC14A1 glycoprotein.