Defective CUBN does not transport GIF:Cbl

Stable Identifier
R-HSA-3296462
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
10080186 Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Aminoff, M, Carter, JE, Chadwick, RB, Johnson, C, Gräsbeck, R, Abdelaal, MA, Broch, H, Jenner, LB, Verroust, PJ, Moestrup, SK, de la Chapelle, A, Krahe, R

Nat. Genet. 1999
13852753 Idiopathic chronic megaloblastic anemia in children

IMERSLUND, O

Acta Paediatr Suppl 1960
13828999 Selective vitamin B12 malabsorption and proteinuria in young people. A syndrome

GRASBECK, R, GORDIN, R, KANTERO, I, KUHLBACK, B

Acta Med Scand 1960
10887099 Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin

Kristiansen, M, Aminoff, M, Jacobsen, C, de la Chapelle, A, Krahe, R, Verroust, PJ, Moestrup, SK

Blood 2000
Participants
Participant Of
Normal reaction
Disease
Name Identifier Synonyms
megaloblastic anemia 13382 megaloblastic anemia, Megaloblastic anemia (disorder), Anaemia - megaloblastic, Megaloblastic anemia NOS (disorder), Megaloblastic anaemia, ANEMIA MEGALOBLASTIC, Megaloblastic anemia NOS, Megaloblastic Anemia, Megaloblastic anemia NOS (disorder), Anaemia - megaloblastic, Megaloblastic anemia, NOS, Megaloblastic anemia NOS
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