Defective TCII does not bind Cbl in the circulation

Stable Identifier
R-HSA-3299657
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Transcobalamin II (TCII, the product of the gene TCN2) is a vitamin B12-binding protein secreted by endothelial cells into plasma that facilitates the endocytosis of cobalamin (Cbl, vitamin B12) into hepatocytes or cells requiring Cbl. Defective TCN2 results in TCN2 deficiency (MIM:275350), an autosomal recessive disorder with early-onset in infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. If left untreated, the disorder can result in mental retardation and neurologic abnormalities (Haberle et al. 2009). In white populations, the most common mutation is pro259arg (P259R). Originally reported as a G-to-C transversion at base position 775 (Miller et al. 2002), it is actually a C-to-G substitution at position 776 (Zetterberg et al. 2003).

Literature References
PubMed ID Title Journal Year
19373259 TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations

Häberle, J, Pauli, S, Berning, C, Koch, HG, Linnebank, M

J. Hum. Genet. 2009
12091374 Transcobalamin II 775G>C polymorphism and indices of vitamin B12 status in healthy older adults

Miller, JW, Ramos, MI, Garrod, MG, Flynn, MA, Green, R

Blood 2002
12707225 The transcobalamin codon 259 polymorphism should be designated 776C>G, not 775G>C

Zetterberg, H, Palmér, M, Boreström, C, Rymo, L, Blennow, K

Blood 2003
Participants
Participates
Normal reaction
Functional status

Loss of function of TCN2 P259R [extracellular region]

Status
Disease
Name Identifier Synonyms
megaloblastic anemia DOID: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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