CXCR4^E343K is associated with WHIM syndrome. (A) Position of mutation E343K in the 7-transmembrane domain model of CXCR4. Small dots represent amino acids except serine (designated by S). The locations of other point mutations reported in WHIM syndrome are also highlighted. (B) Alignment of predicted amino acid sequences from the C-terminal domain of CXCR4^WT and all reported CXCR4 mutants associated with WHIM syndrome. The position mutated to lysine (K) in CXCR4^E343K is highlighted. *Missense mutation that extends the sequence by an additional 10 amino acids, not shown for clarity. (C) The glutamic acid changed to lysine in CXCR4^E343K is highly conserved phylogenetically. Predicted amino acid sequences from the C-terminal domain of CXCR^WT are aligned for the indicated species. The homology (percent amino acid identity) of human CXCR4 to CXCR4 from each of the other species listed is shown for both the full-length sequence and the C-terminal 19 amino acids.