X-chromosome-linked agammaglobulinemia (XLA) is an example of a disease where mutations are present in the SH2 domain of the Bruton's tyrosine kinase (BTK), and many of these mutations are located on the pTyr-ligand binding site, including the indispensable arginine of the pTyr-binding pocket as well as BG loop residues [16,173]. The gene discussed is BTK; the disease is Bruton-type agammaglobulinemia.