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How Your TCN2 Gene Affects Vitamin B12 Transport and Why It Matters

Vitamin B12 is an essential nutrient that supports nerve health, brain function, red blood cell formation, and DNA synthesis. Because the body cannot make B12, you must get it from animal-based foods such as meat, fish, eggs, and dairy, or from fortified plant-based foods. The TCN2 gene makes transcobalamin II, a protein that carries Vitamin B12 through the bloodstream and delivers it into cells. Variations in TCN2 can change how efficiently B12 reaches your cells, which may lower functional B12 levels even if dietary intake appears adequate.

This article explains what different genotypes for rs9606756 in TCN2 may mean for your B12 status, practical diet and lifestyle choices to support healthy levels, and how to monitor and discuss options with your healthcare provider. PlexusDx does not provide medical advice. This information is educational about genetic predispositions only. Always consult your healthcare provider before starting supplements or making major changes to your diet or treatment plan.

Quick overview: Why transport matters

  • Dietary intake supplies B12 to your bloodstream, but transcobalamin II is required to shuttle B12 into cells.
  • If transcobalamin II binds or transports B12 less efficiently, total blood B12 may be normal but cellular B12 can be low.
  • Low functional B12 can affect energy, nerve function, cognition, and red blood cell production.

Signs that B12 may be low

  • Fatigue or low energy
  • Numbness, tingling, or other nerve symptoms
  • Memory or concentration problems
  • Unexplained anemia

Genetic interpretations for rs9606756 (TCN2)

2 effect alleles — GG (higher likelihood of reduced B12 transport)

If your genotype is GG, you carry two copies of the effect allele. This variation in TCN2 is associated with reduced efficiency of transcobalamin II to bind and deliver Vitamin B12 into cells. As a result, your cells may receive less B12 even when your dietary intake seems adequate. That could increase risk of functional B12 deficiency over time, which may affect energy metabolism, nerve health, cognitive function, and red blood cell production.

Practical steps to consider

  • Prioritize B12-rich foods: regular servings of meat, fish, eggs, and dairy.
  • If you are vegetarian or vegan, regularly consume fortified foods such as plant-based milks, breakfast cereals, and nutritional yeast.
  • Discuss the option of oral B12 supplements or methylcobalamin/cyanocobalamin injections with your healthcare provider, especially if symptoms or lab results suggest deficiency.
  • Ask your provider about functional B12 testing: serum B12, methylmalonic acid (MMA), and homocysteine can help show cellular B12 status.
  • Monitor symptoms and repeat labs as recommended by your provider to ensure treatment or dietary strategies are effective.
1 effect allele — AG (possible reduced B12 transport)

If your genotype is AG, you carry one copy of the effect allele. This genotype is associated with a change in transcobalamin II function that may reduce the efficiency of B12 binding and transport to cells. The effect is usually less pronounced than with two effect alleles, but it can still contribute to lower cellular B12 availability, particularly when other risk factors are present (for example, low dietary intake, gastrointestinal conditions that impair absorption, or certain medications).

Practical steps to consider

  • Include B12-rich foods regularly: meat, fish, eggs, and dairy.
  • If you follow a plant-based diet, use fortified foods consistently and consider a reliable supplemental source.
  • Talk with your healthcare provider about testing serum B12, MMA, and homocysteine if you have symptoms or other risk factors.
  • Consider a trial of supplementation under medical supervision if labs or symptoms suggest borderline or low B12.
0 effect alleles — AA (typical B12 transport)

If your genotype is AA, you carry two copies of the non-effect allele. This genotype is associated with typical transcobalamin II function and standard capacity to transport Vitamin B12 into cells. With a balanced diet that includes B12-containing foods or fortified foods when appropriate, most people with this genotype maintain healthy B12 status.

Practical steps to consider

  • Continue regular intake of B12-rich foods such as meat, fish, eggs, and dairy.
  • If you follow a vegetarian or vegan diet, include fortified foods and consider routine supplementation to meet needs.
  • If you experience symptoms of deficiency or have medical conditions that affect absorption, speak with your healthcare provider about testing.

Dietary strategies

  • Animal sources: Beef, poultry, pork, fish (especially shellfish and oily fish), eggs, and dairy provide preformed B12 that is readily absorbed.
  • Fortified plant-based options: Many plant milks, breakfast cereals, and nutritional yeast are fortified with B12. Check labels for cyanocobalamin or methylcobalamin content.
  • Consistency matters: If you limit or avoid animal products, rely on fortified foods or supplements daily to maintain stores.

Supplements and monitoring

  • Forms: Cyanocobalamin is stable and commonly used; methylcobalamin is an active form some prefer. Your healthcare provider can advise which is right for you.
  • Dosing: Routine low-dose supplements can maintain levels for many people. Higher doses or injections may be recommended for documented deficiency or malabsorption conditions.
  • Labs: Ask about serum B12, methylmalonic acid (MMA), and homocysteine testing to assess functional B12 status. Repeat testing after any treatment or significant diet change.

Lifestyle and other considerations

  • Medications and conditions: Some medications and gastrointestinal disorders reduce B12 absorption. Review current medications and medical history with your provider.
  • Aging: Older adults often absorb less B12 from food and may benefit from fortified foods or supplements.
  • Symptom tracking: Note fatigue, neurological changes, mood or cognitive changes, and any signs of anemia. Share these with your provider for targeted evaluation.

Next steps and talking to your provider

  • Share your genetic result and any symptoms with your healthcare provider.
  • Consider baseline testing for serum B12, MMA, and homocysteine if you have symptoms or risk factors.
  • Work with your provider to determine if dietary changes, supplements, or other interventions are appropriate and to set up follow-up testing.

PlexusDx does not provide medical advice. This information is intended to educate you about genetic predispositions only. Always consult your healthcare provider for personalized medical guidance and before starting supplements or making significant changes to your diet or treatment.