Piezo1 protein (Uniprot Q92508) amino acids 602 to 2521 and known mutations in PIEZO1 encoding amino acid substitutions. Er blood group antigens encoded by PIEZO1 are given in red and as detailed by Karamatic Crew et al.1 Gly2394 is required for expression of the high-prevalence antigen Era, whereas Ser2394 encodes the antithetical low-prevalence antigen Erb. Proposed novel high-prevalence antigens Er4 and Er5 are associated, respectively, with Gln2407 and Arg2245 in Piezo1. One Er3-negative allele encodes wild-type Gly2394 (Era) with a nearby Glu2392Lys mutation. Exemplary mutations of PIEZO1 with resulting amino acid exchanges reported for patients with DHS are given in blue and are del756, Pro1358, Arg2225, Thr2020, and His2456. Exemplary mutations of PIEZO1 with resulting amino acid exchanges reported for patients with LMPHM6 are given in black and are Ter755, Ter1630, and Phe2171. All Er blood group antigens cluster in the carboxy-terminal loop of Piezo1. Dominant mutations causing DHS and LMPHM6 mutations following a recessive mode of inheritance may be observed throughout all parts of Piezo1. The position of the PIEZO1 mutations suggest coding of disease-associated alleles for blood group antigens and, vice versa, blood group antigens that may simultaneously represent disease-associated alleles. However, this hypothesis requires further research. Graphic generated in Protter.

Piezo1 protein (Uniprot Q92508) amino acids 602 to 2521 and known mutations in PIEZO1 encoding amino acid substitutions. Er blood group antigens encoded by PIEZO1 are given in red and as detailed by Karamatic Crew et al.1 Gly2394 is required for expression of the high-prevalence antigen Era, whereas Ser2394 encodes the antithetical low-prevalence antigen Erb. Proposed novel high-prevalence antigens Er4 and Er5 are associated, respectively, with Gln2407 and Arg2245 in Piezo1. One Er3-negative allele encodes wild-type Gly2394 (Era) with a nearby Glu2392Lys mutation. Exemplary mutations of PIEZO1 with resulting amino acid exchanges reported for patients with DHS are given in blue and are del756, Pro1358, Arg2225, Thr2020, and His2456. Exemplary mutations of PIEZO1 with resulting amino acid exchanges reported for patients with LMPHM6 are given in black and are Ter755, Ter1630, and Phe2171. All Er blood group antigens cluster in the carboxy-terminal loop of Piezo1. Dominant mutations causing DHS and LMPHM6 mutations following a recessive mode of inheritance may be observed throughout all parts of Piezo1. The position of the PIEZO1 mutations suggest coding of disease-associated alleles for blood group antigens and, vice versa, blood group antigens that may simultaneously represent disease-associated alleles. However, this hypothesis requires further research. Graphic generated in Protter.

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