A) 3D mapping of common BTK missense mutations associated with resistance to multiple BTK inhibitors (previously published in Sharma et al, PMID: 27626698). B) Clinically reported BTK mutations in patients treated with ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib. Note that not all mapped mutations have been functionally validated. PH, pleckstrin homology domain; TH, Tec homology domain; SH, Src homology domain; Tyrosine kinase, tyrosine kinase domain. The height of the vertical bars represents the relevant abundance of the particular variants. *Experimentally predicted to be resistant to multiple BTK inhibitors. The graph was generated with BioRender.