WCN26-3555 Altered Localization of the CUBN–AMN Complex in Renal Tissue of a Patient with PROCHOB

Cubilin (CUBN) is expressed at the proximal tubule brush border, where it forms a complex with Amnionless (AMN) at its N-terminus to mediate albumin reabsorption. AMN and CUBN are known to be interdependent for their plasma membrane expression. Because CUBN forms a complex with AMN at its N-terminus, pathogenic variants in the CUBN N-terminus or AMN result in the failure of CUBN to be expressed at the cell membrane. Since CUBN is also involved in vitamin B12 absorption in the small intestine, pathogenic variants in the CUBN N-terminus or AMN have long been known to cause Imerslund-Gräsbeck Syndrome (IGS), characterized by tubular proteinuria and megaloblastic anemia due to vitamin B12 malabsorption.