HX-associated PIEZO1 mutations. (A) The position of the 6 PIEZO1 mutations identified in this report and the first 2 HX-associated PIEZO1 mutations described, R2456H and M2225R, are shown on a model of PIEZO1 derived from the cryoelectron microscopy structure.²¹  The locations of the channel anchor, the peripheral helices (PH), the inner helices (IH), and the outer helices (OH) are shown. (B) Conservation of HX-associated mutant amino acids. The 4 amino acids located in the COOH-terminal domain containing the putative PIEZO1 channel exhibit high degrees of conservation.