Fig. 4

The structural and functional diversity of KLRC2 in humans. a The proportion of three KLRC haplotypes is shown in a pie chart. The KLRC_hap1 represents one copy of KLCR2 shown in purple. The KLRC_hap2 represents zero copies of KLCR2 shown in orange. The KLRC_hap3 represents two copies of KLCR2 shown in dark blue. Distributions of KLRC_hap1 (purple), KLRC_hap2 (orange), and KLRC_hap3 (blue) inferred from the 1 KG human population data across the world are shown on the right panel. b The phylogenetic tree of the KLRC haplotype genomic regions shows KLRC-hap2 (KLRC2 depletion) is a result of a single-deletion event. The red and blue rectangles show KLRC-hap2 and KLRC-hap3, respectively. The rest of the humans belong to KLRC-hap1. The super population of each human is listed with five color dots. c The genomic region (chr12:10,000,000–10,700,000 in GRCh38) with assembled BAC clone, gene, segdup, and LD (D’) annotation shows that the KLRC gene cluster is probably linked together. The six SNVs distinguished between KLRC-hap2 and KLRC-hap1 are represented in the cyan lines with their SNP ID. The heatmaps of LD indexes (R2 and D’) show that the six SNVs are highly linked in humans. d Consistent patterns of associations between the six SNVs and expression levels of KLRC2 in 35 tissues are shown in the multi-tissue eQTL plots. The positive normalized effect size (NES) values represent the effect of the higher expression on the alternative allele (purple) relative to the reference allele (red). The (unadjusted) p-values of the eQTL association are shown in the size variable dots. The allele frequencies of the six SNVs in the gnomAD database are shown on the right. e The PheWAS plots for three SNVs (rs1382264, rs2617151, and rs2733845) are significantly associated with immune domain differentiation across GWAS in the GWASALAS database. The particular traits (NKearly:%335 + 314- and NKeff:%314-R7-) are marked with significant signals [45]