Understanding Vitamin B12 and the TCN1 Gene
Vitamin B12 is essential for nerve health, brain function, red blood cell formation, and DNA synthesis. The TCN1 gene produces transcobalamin I, a protein that binds most circulating Vitamin B12 in the stomach and bloodstream. Variations in TCN1 can change how well this protein binds and protects B12, which may influence circulating B12 levels. Having a genetic variant that is associated with lower circulating B12 does not guarantee deficiency, especially if dietary intake and absorption are good. This article explains what the common rs526934 genotypes mean, practical ways to support B12 status through diet, supplements, lifestyle, and which blood tests may help monitor B12 health.
How genetics fit with diet and absorption
Your genes can influence how Vitamin B12 is carried and protected in the blood, but absorption and intake play major roles too. The stomach must release B12 from food, intrinsic factor from stomach cells is needed for intestinal absorption, and the liver stores B12 for years. Genetic changes in TCN1 affect binding in the stomach and bloodstream and can slightly alter circulating levels. If you eat sufficient B12-rich foods or take appropriate supplements, many people with a risk variant do fine. Still, gene information can help you and your healthcare provider decide whether testing or dietary changes are useful.
Genetic Result Interpretations
2 effect alleles (GG) — Higher likelihood of lower circulating B12
Your GG genotype at rs526934 is associated with lower circulating Vitamin B12. The TCN1 protein you make may be less efficient at binding and protecting B12 in the stomach and blood. This may reduce the portion of B12 that is readily available for cellular use.
What this can mean for you
- You may have lower serum B12 levels compared with people without this variant, especially if dietary intake or absorption is marginal.
- Symptoms of B12 deficiency are not guaranteed. Many people maintain normal function with good diet or supplements.
- Consider more proactive monitoring and nutritional strategies if you have other risk factors for low B12 such as vegetarian/vegan diet, older age, history of gastric surgery, chronic antacid or metformin use, or autoimmune gastritis.
Practical steps
- Diet: Prioritize animal-based B12 sources: beef, poultry, fish, shellfish, eggs, and dairy. Fortified plant milks, breakfast cereals, and nutritional yeast are important for plant-based diets.
- Supplements: Consider daily oral B12 supplement if diet is inadequate. Forms include methylcobalamin, cyanocobalamin, or hydroxocobalamin. Higher oral doses or monthly intramuscular injections may be recommended if you have absorption issues.
- Lifestyle: Maintain a balanced diet, reduce heavy alcohol use, and avoid unnecessary long-term use of proton pump inhibitors without medical oversight.
- Testing: Discuss with your healthcare provider about measuring serum B12, methylmalonic acid, and homocysteine to assess functional B12 status.
1 effect allele (AG) — Possible modest reduction in circulating B12
Your AG genotype suggests a possible modest reduction in circulating Vitamin B12 compared with the non-effect genotype. The transcobalamin I protein may function slightly less efficiently, but many people with this genotype maintain adequate B12 if intake and absorption are sufficient.
What this can mean for you
- Risk is generally smaller than for two effect alleles, but the variant indicates slightly increased sensitivity to low dietary intake or absorption problems.
- No immediate symptoms are expected if your diet includes regular B12 sources or fortified foods, but monitoring and preventive measures are prudent.
Practical steps
- Diet: Include regular servings of B12-rich foods or fortified products. For plant-based diets, plan fortified foods or supplements into your routine.
- Supplements: Consider a daily low-dose B12 supplement if you have limited animal foods in your diet or other risk factors for poor absorption.
- Testing: If you have symptoms like fatigue, numbness, or memory concerns, or if you take medications that affect B12 absorption, discuss testing with your provider.
0 effect alleles (AA) — Typical circulating B12 support from TCN1
Your AA genotype is associated with typical transcobalamin I function and standard circulating B12 levels from this genetic locus. This means your TCN1-related B12 transport is not expected to contribute to lower circulating B12.
What this can mean for you
- You have typical genetic support for B12 transport from TCN1, but other factors can still cause low B12.
- Diet, age, medications, stomach health, and other genetics still matter for total B12 status.
Practical steps
- Diet: Continue to eat B12-rich foods or fortified alternatives as needed by your dietary pattern.
- Supplements: Use supplements when clinically recommended, such as for strict vegan diets, older adults, or diagnosed malabsorption.
- Testing: Routine testing is not required solely based on this genotype, but discuss testing if you have symptoms or other risk factors.
Diet, Supplements, and Lifestyle Recommendations
Dietary choices and absorption are the primary determinants of B12 status. Use the guidance below to maintain healthy levels based on your lifestyle and genetic result.
Foods to include
- Animal sources: beef, lamb, poultry, fish, shellfish, eggs, and dairy provide bioavailable B12.
- Fortified options: plant milks, breakfast cereals, and nutritional yeast labeled with B12 are essential for vegetarians and vegans.
- Eating a variety of B12-rich foods across the week helps maintain stores.
Supplement options
- Oral supplements: daily low-dose supplements are effective for prevention. Common forms include methylcobalamin and cyanocobalamin.
- High-dose oral therapy: useful when absorption may be reduced; high doses can be absorbed passively without intrinsic factor.
- Injectable B12: intramuscular injections are used when severe malabsorption or deficiency is present; these are prescribed and administered by a healthcare professional.
- Work with your healthcare provider to choose dose and form based on diet, age, and GI health.
Lifestyle factors
- Avoid excessive alcohol which can impair absorption and liver storage.
- Discuss long-term acid suppression therapy and metformin use with your provider since these can lower B12 over time.
- Maintain routine health care and screenings, especially if you are older or have digestive disorders.
Recommended Tests and When to Consider Them
- Serum Vitamin B12: initial screening test for B12 concentration.
- Methylmalonic acid (MMA): a more sensitive marker of functional B12 deficiency; elevated MMA suggests inadequate cellular B12.
- Homocysteine: can be elevated with B12 deficiency but is also influenced by folate and B6 status.
- Intrinsic factor antibodies or parietal cell antibodies: considered when autoimmune gastritis or pernicious anemia is suspected.
- Work with your healthcare provider to interpret results in the context of symptoms, medications, and other labs.
Important Notes and Disclaimer
PlexusDx does not provide medical advice. The information in this article is educational and describes how a TCN1 genetic variant may relate to Vitamin B12 transport and circulating levels. Genetic results are one piece of the health puzzle and should be combined with dietary assessment, clinical history, and laboratory testing. Always consult your healthcare provider before making changes to diet, supplement use, or treatment decisions. Your provider can help interpret genetic and blood test results and recommend appropriate monitoring or interventions tailored to your health needs.

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Molybdenum | AOX1 (rs55754655)
Molybdenum | AOX1 (rs55754655)