In preparation for internalisation, the gastric intrinsic factor:cobalamin (GIF:Cbl) complex interacts with the cubilin:protein amnionless complex (CUBN:AMN, Cubam). CUBN is a multisubstrate cell surface receptor facilitating uptake of lipoproteins, vitamins and iron. Protein amnionless (AMN) is a necessary component which directs subcellular localization and endocytosis of GIF:Cbl. Defects in AMN cause recessive hereditary megaloblastic anemia 1 (RH-MGA1 aka MGA1 Norwegian type or Imerslund-Grasbeck syndrome, I-GS; MIM:261100). The Finnish cases described by Grasbeck et al. were caused by defects in CUBN whereas the Norwegian cases described by Imerslund were due to defects in AMN (Grasbeck et al. 1960, Imerslund 1960 respectively). The resultant malabsorption of Cbl (vitamin B12) leads to impaired B12-dependent folate metabolism and ultimately impaired thymine synthesis and DNA replication. Cells involved in erythropoiesis are particularly affected. Two common mutations in AMN are T34I and G5Afs*12 (Tanner et al. 2003).
IMERSLUND, O
Liyanarachchi, S, Tanner, SM, Kuronen, M, Wright, FA, Broch, H, Mandel, H, Massika, O, Aminoff, M, de la Chapelle, A, Saarinen, A
KANTERO, I, KUHLBACK, B, GORDIN, R, GRASBECK, R
Loss of function of CUBN:AMN mutants [plasma membrane]
© 2022 Reactome
