Hypomorphic <i>ATP11c</i> is a novel regulator of decreased efficacy of transfused red blood cells in humans and mice.

ABSTRACT: Chronic red blood cell (RBC) transfusion sustains patients with diverse hematologic disorders, but repeated transfusion leads to iron overload and alloimmunization. Reducing transfusion burden requires identifying donor units that circulate more effectively after storage, yet determinants of this variability remain incompletely defined. Here, we integrate forward genetics in mice, multi-omics analyses of over 13,000 human donors, and studies of two families with hereditary ATP11c mutations to reveal a central role for this phospholipid flippase in transfusion efficacy. We show that common ATP11C variants, including the missense SNP V972M, and rare familial loss-of-function alleles impair RBC survival by disrupting membrane lipid remodeling and cytoskeletal stability-a mechanism distinct fr

SUBMITTER: Zimring JC 

PROVIDER: S-EPMC12784117 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature