In preparation for internalisation, the gastric intrinsic factor:cobalamin (GIF:Cbl) complex interacts with the cubilin:protein amnionless complex (CUBN:AMN). CUBN is a cotransporter 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 CUBN cause recessive hereditary megaloblastic anemia 1 (RH-MGA1 aka MGA1 Finnish 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. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries, in Norway and highest in Finland (0.8 in 100,000). The P1297L mutation in CUBN is most commonly found in Finland (Aminoff et al. 1999, Kristiansen et al. 2000).
IMERSLUND, O
Verroust, PJ, Gräsbeck, R, Broch, H, Moestrup, SK, Johnson, C, Jenner, LB, de la Chapelle, A, Krahe, R, Abdelaal, MA, Carter, JE, Chadwick, RB, Aminoff, M
KANTERO, I, KUHLBACK, B, GORDIN, R, GRASBECK, R
Verroust, PJ, Moestrup, SK, de la Chapelle, A, Jacobsen, C, Krahe, R, Aminoff, M, Kristiansen, M
Loss of function of CUBN P1297L:AMN [plasma membrane]
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