A SLC14A1 c.230G>A variant causes loss of Kidd antigen expression
- 1Blood Center of Zhejiang Province
Abstract
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.
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BibTeX
@article{hong2026slc14a1,
title = {{A SLC14A1 c.230G>A variant causes loss of Kidd antigen expression}},
author = {Xiaozhen Hong and Jingjing Zhang and Yanling Ying and Xianguo Xu and Faming Zhu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1922509},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1922509/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A SLC14A1 c.230G>A variant causes loss of Kidd antigen expression
AU - Xiaozhen Hong
AU - Jingjing Zhang
AU - Yanling Ying
AU - Xianguo Xu
AU - Faming Zhu
PY - 2026
DA - 2026/10/29
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1922509
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1922509/full
AB - 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.
SN - 1664-3224
ER -