Somatic CXCR4 mutations in WM are similar to those found in WHIM syndrome. Somatic CXCR4 nonsense and frameshift mutations found in 177 WM patient samples. (A) Protein sequence for the canonical full-length transcript (NP_003458.1) demonstrates that similar to the variants responsible for WHIM syndrome, these mutations result in a truncation of the cytosolic tail containing the regulatory phospho-serines leaving the seven transmembrane helix region involved in signaling and ligand binding intact. (B) The crystal structure of homodimeric CXCR4 with the carboxyl terminal tail highlighted in yellow and indicated by the white arrows. (C) Precise location and number of WHIM-like somatic mutations in WM at transcript level and detailed mutation-type summary of the most frequently mutated amino acid, S338.