{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:16:18Z","timestamp":1790702178482,"version":"4.1.0"},"reference-count":41,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite the identification of the high-incidence red cell antigen Era nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR\/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line. We report the molecular bases of 5 Er blood group antigens: the recognized Era, Erb, and Er3 antigens and 2 novel high-incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn. Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low-abundance membrane proteins and contributes to our understanding of the in\u00a0vivo characteristics of this important and widely studied protein in transfusion biology and beyond.<\/jats:p>","DOI":"10.1182\/blood.2022016504","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T16:59:08Z","timestamp":1663606748000},"page":"135-146","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":32,"title":["Missense mutations in\n                    <i>PIEZO1,<\/i>\n                    which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-9107","authenticated-orcid":false,"given":"Vanja","family":"Karamatic Crew","sequence":"first","affiliation":[{"name":"1International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8244-4331","authenticated-orcid":false,"given":"Louise A.","family":"Tilley","sequence":"additional","affiliation":[{"name":"1International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-292X","authenticated-orcid":false,"given":"Timothy J.","family":"Satchwell","sequence":"additional","affiliation":[{"name":"2School of Biochemistry, University of Bristol, Bristol, United Kingdom"},{"name":"3National Institute for Health Research Blood and Transplant Research Unit in Red Blood Cell Products, University of Bristol, Bristol, United Kingdom"},{"name":"4Bristol Institute of Transfusion Sciences, NHS Blood and Transplant, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah A.","family":"AlSubhi","sequence":"additional","affiliation":[{"name":"1International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol, United Kingdom"},{"name":"2School of Biochemistry, University of Bristol, Bristol, United Kingdom"},{"name":"5Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Jones","sequence":"additional","affiliation":[{"name":"1International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances 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Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Alradwan","sequence":"additional","affiliation":[{"name":"10Kuwait Central Blood Bank, Hawally, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouza","family":"AlKhrousey","sequence":"additional","affiliation":[{"name":"10Kuwait Central Blood Bank, Hawally, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Skidmore","sequence":"additional","affiliation":[{"name":"11Red Cell Immunohaematology, NHS Blood and Transplant, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lewis","sequence":"additional","affiliation":[{"name":"11Red Cell Immunohaematology, NHS Blood and Transplant, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Hussain","sequence":"additional","affiliation":[{"name":"11Red Cell Immunohaematology, NHS Blood and Transplant, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Jackson","sequence":"additional","affiliation":[{"name":"12Haematology Department at Birmingham Women\u2019s Hospital, Birmingham Women\u2019s and Children\u2019s NHS Foundation Trust, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Latham","sequence":"additional","affiliation":[{"name":"13NHS Blood and Transplant, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-4223","authenticated-orcid":false,"given":"Mark D.","family":"Kilby","sequence":"additional","affiliation":[{"name":"14College of Medical & Dental Sciences, University of Birmingham, Birmingham, United Kingdom"},{"name":"15Fetal Medicine Centre, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United 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