Vitamin B12

Vitamin B12 plays key roles in several biological processes, such as DNA synthesis and regulation, energy production and erythropoiesis (red blood cells production).

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Vitamin B12 deficiency is clinically associated with megaloblastic anemia, neurological disorders like mania, psychosis, and cognitive impairment such as memory loss. Deficiency in B12 elevates methylmalonic acid and homocysteine.

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High homocystaine levels result in irritation, migraines, neurological disorders, anemia, risk for cardiovascular disease and more.

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Most cases of vitamin B12 deficiency are due to poor absorption. Heritable genetic variations are accounted for at least a third of all B12 malabsorption cases. Here are the genes involved in genetic susceptibility to vitamin B12 deficiency:

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Gene: TRANSCOBALAMIN I (TCN1)

Genomic coordinates (GRCh38): 11:59,852,807-59,866,567

TCN1 is a vitamin B12 binding protein that promotes the cellular uptake of vitamin B12. The TCN1 G variant may reduce transport of cobalamin, resulting in lower plasma vitamin B12 levels.

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Gene: TRANSCOBALAMIN II (TCN2)
Genomic coordinates (GRCh38): 22:30,607,082-30,627,059

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The TCN2 gene encodes transcobalamin II (TC II), a plasma globulin that acts as the primary transport protein for vitamin B12. Variant form is less efficient in delivering B12 to tissues, and may thus influence susceptibility to B12 deficiency.
 

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Gene: CUBILIN (CUBN)
Genomic coordinates (GRCh38): 10:16,823,965-17,130,491

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CUBN produces a cobalamin receptor. A missense mutation in exon 8 is predicted to decrease CUBN functionality, thereby lowering vitamin B-12 absorption.
 

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