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Primary topic: TCN2 B12 transport gene

TCN2 Gene and Metabolism: What It Means for Your Body

TCN2 helps move vitamin B12 into tissues, so it matters when methylation support looks weak despite reasonable B12 intake.

What is the TCN2 gene?

TCN2 encodes transcobalamin, the carrier that delivers vitamin B12 to cells. Without effective transport, serum B12 can look adequate while functional B12 support inside tissues still falls short.

How TCN2 affects metabolism

If TCN2-related transport is less efficient, methylation and red-blood-cell support can run with less available B12 than expected. That can create pressure on homocysteine handling, energy support, and neurological resilience.

What happens when TCN2 is altered

Altered TCN2 function does not guarantee deficiency, but it increases the value of checking functional B12 markers instead of relying on total intake or one standard lab value.

Curated SNP evidence for TCN2

These SNPs come from the approved study-level evidence model. Each claim is scored from curated study rows, then gated before it can influence pathway scoring.

B12 transport Choline support Methylation

Evidence-backed report connection

TCN2 currently has 3 curated SNPs, 7 claim-level scores, and 1 claims eligible for pathway scoring.

Open the sample report
rs1131603TCN2 vitamin B12 status signal1 claims · 4 study rows

biomarker tendency · TT

Vitamin B12 status tendency

Moderate

rs1131603 TT carries two T alleles in TCN2 and is associated with lower vitamin B12 status tendency.

TCN2 rs1131603 TT is staged as a lower vitamin-B12-status genotype within B12 transport and remethylation context.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP identifies rs1131603 as a chromosome 22 TCN2-region variant with T/C alleles. This row supports variant identity only and does not assign B12-status direction.PubMed 23754956gwas · directGrarup et al. reported rs1131603 at TCN2 as a serum vitamin B12 locus. Public summaries of the study report the C allele as B12-increasing with beta about 0.19 and strong genome-wide significance; at this C/T biallelic locus, that supports T as lower B12 status relative to C.GWAS Catalog association 106202384gwas · directGWAS Catalog records rs1131603-C for vitamin B12 measurement at genome-wide significance. Because C is the vitamin B12-increasing allele in this C/T locus, this supports T as the lower B12-status allele by contrast.GWAS Catalog association 163385781gwas · close proxyGWAS Catalog records rs1131603-T for vitamin B12 deficiency with beta direction increase, beta 0.3565, SE 0.04763, and P = 5e-25. For the B12-status target, higher B12-deficiency liability supports a lower B12-status direction for T.
rs1801198C776G3 claims · 6 study rows

biomarker tendency · CG

TCN2 biomarker tendency

Not used for pathway scoring

rs1801198 CG is associated with reduced TCN2 biomarker tendency.

TCN2 rs1801198 is scored as a tendency toward lower holotranscobalamin for G-containing genotypes, strongest for GG.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1801198 in TCN2, the gene for transcobalamin 2. The common c.776G>C annotation is a missense variant in the TCN2 transcript, supporting curation as a vitamin B12 transport-related biomarker signal rather than an enzyme variant.PubMed 28814397review · close proxyA systematic review and meta-analysis of 34 studies reported that the TCN2 rs1801198 GG genotype was associated with lower holotranscobalamin and, in European-descent subjects, slightly higher homocysteine compared with CC. The same review found no significant genotype difference for total cobalamin, folate, or red blood cell folate, and no significant primary association with congenital abnormalities, cancer, or Alzheimer disease.

biomarker tendency · GG

TCN2 biomarker tendency

Not used for pathway scoring

rs1801198 GG is associated with reduced TCN2 biomarker tendency.

TCN2 rs1801198 is scored as a tendency toward lower holotranscobalamin for G-containing genotypes, strongest for GG.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1801198 in TCN2, the gene for transcobalamin 2. The common c.776G>C annotation is a missense variant in the TCN2 transcript, supporting curation as a vitamin B12 transport-related biomarker signal rather than an enzyme variant.PubMed 28814397review · close proxyA systematic review and meta-analysis of 34 studies reported that the TCN2 rs1801198 GG genotype was associated with lower holotranscobalamin and, in European-descent subjects, slightly higher homocysteine compared with CC. The same review found no significant genotype difference for total cobalamin, folate, or red blood cell folate, and no significant primary association with congenital abnormalities, cancer, or Alzheimer disease.

biomarker tendency · CC

TCN2 biomarker tendency

Not used for pathway scoring

rs1801198 CC has no scored directional claim for TCN2 biomarker tendency.

TCN2 rs1801198 is scored as a tendency toward lower holotranscobalamin for G-containing genotypes, strongest for GG.

Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1801198 in TCN2, the gene for transcobalamin 2. The common c.776G>C annotation is a missense variant in the TCN2 transcript, supporting curation as a vitamin B12 transport-related biomarker signal rather than an enzyme variant.PubMed 28814397review · close proxyA systematic review and meta-analysis of 34 studies reported that the TCN2 rs1801198 GG genotype was associated with lower holotranscobalamin and, in European-descent subjects, slightly higher homocysteine compared with CC. The same review found no significant genotype difference for total cobalamin, folate, or red blood cell folate, and no significant primary association with congenital abnormalities, cancer, or Alzheimer disease.
rs9606756TCN2 supporting signal3 claims · 12 study rows

unknown · AA

TCN2 unscored target

Not used for pathway scoring

rs9606756 AA has no scored directional claim for TCN2 unscored target.

TCN2 rs9606756 is currently kept as an unscored variant because available sources do not support a clear end-user genotype effect.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs9606756 as an A/G variant in TCN2. Transcript annotations include NM_000355.4:c.67A>G with a predicted p.Ile23Val protein change, so the variant is plausibly relevant to transcobalamin biology but this source alone does not establish a measured genotype-level functional effect.Evidence 2other · loose proxyNCBI Gene summarizes TCN2 as encoding a vitamin B12-binding plasma protein that binds cobalamin and helps transport cobalamin into cells. This supports the biological relevance of TCN2 for vitamin B12 handling, but it does not show that rs9606756 itself changes transport activity.PubMed 28417558biomarker association · loose proxyHebbar et al. reported that rs9606756 was associated with waist circumference in an Arab cohort and described an interaction involving Apo-A1 or HDL levels. This is an anthropometric association study, not a direct assay of TCN2 transport activity or a reliable basis for assigning a simple vitamin B12 direction to AA, AG, or GG genotypes.PMC5801754review · loose proxyA review of vitamin B12-related gene polymorphisms lists mixed population evidence for rs9606756, including a reported association with holotranscobalamin in one cohort and no association with plasma cobalamin in other cohorts. This supports leaving the genotype effect neutral until stronger direct functional or replicated biomarker evidence is available.

unknown · AG

TCN2 unscored target

Not used for pathway scoring

rs9606756 AG has no scored directional claim for TCN2 unscored target.

TCN2 rs9606756 is currently kept as an unscored variant because available sources do not support a clear end-user genotype effect.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs9606756 as an A/G variant in TCN2. Transcript annotations include NM_000355.4:c.67A>G with a predicted p.Ile23Val protein change, so the variant is plausibly relevant to transcobalamin biology but this source alone does not establish a measured genotype-level functional effect.Evidence 2other · loose proxyNCBI Gene summarizes TCN2 as encoding a vitamin B12-binding plasma protein that binds cobalamin and helps transport cobalamin into cells. This supports the biological relevance of TCN2 for vitamin B12 handling, but it does not show that rs9606756 itself changes transport activity.PubMed 28417558biomarker association · loose proxyHebbar et al. reported that rs9606756 was associated with waist circumference in an Arab cohort and described an interaction involving Apo-A1 or HDL levels. This is an anthropometric association study, not a direct assay of TCN2 transport activity or a reliable basis for assigning a simple vitamin B12 direction to AA, AG, or GG genotypes.PMC5801754review · loose proxyA review of vitamin B12-related gene polymorphisms lists mixed population evidence for rs9606756, including a reported association with holotranscobalamin in one cohort and no association with plasma cobalamin in other cohorts. This supports leaving the genotype effect neutral until stronger direct functional or replicated biomarker evidence is available.

unknown · GG

TCN2 unscored target

Not used for pathway scoring

rs9606756 GG has no scored directional claim for TCN2 unscored target.

TCN2 rs9606756 is currently kept as an unscored variant because available sources do not support a clear end-user genotype effect.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs9606756 as an A/G variant in TCN2. Transcript annotations include NM_000355.4:c.67A>G with a predicted p.Ile23Val protein change, so the variant is plausibly relevant to transcobalamin biology but this source alone does not establish a measured genotype-level functional effect.Evidence 2other · loose proxyNCBI Gene summarizes TCN2 as encoding a vitamin B12-binding plasma protein that binds cobalamin and helps transport cobalamin into cells. This supports the biological relevance of TCN2 for vitamin B12 handling, but it does not show that rs9606756 itself changes transport activity.PubMed 28417558biomarker association · loose proxyHebbar et al. reported that rs9606756 was associated with waist circumference in an Arab cohort and described an interaction involving Apo-A1 or HDL levels. This is an anthropometric association study, not a direct assay of TCN2 transport activity or a reliable basis for assigning a simple vitamin B12 direction to AA, AG, or GG genotypes.PMC5801754review · loose proxyA review of vitamin B12-related gene polymorphisms lists mixed population evidence for rs9606756, including a reported association with holotranscobalamin in one cohort and no association with plasma cobalamin in other cohorts. This supports leaving the genotype effect neutral until stronger direct functional or replicated biomarker evidence is available.

Common symptoms people report

  • fatigue despite supplementing B12
  • brain fog or slower mental processing
  • tingling or low neurological resilience
  • homocysteine concerns despite acceptable diet

Biomarkers to validate

Holotranscobalamin

Useful for seeing the biologically available fraction of circulating B12.

Methylmalonic acid

Helps detect whether B12 is functionally sufficient inside cells.

Homocysteine

Adds context for whether methylation support appears stressed.

Where DNA analysis helps

DNA analysis can flag B12 transport as a pathway worth validating when symptom patterns or methylation markers do not fully make sense. The purpose is prioritization, not diagnosis.

Example Insight

Your B12 delivery pathway may be less efficient than serum intake alone suggests.

Suggested validation: holotranscobalamin and methylmalonic acid.

What to do next

  • Check functional B12 markers before assuming intake is the issue.
  • Compare TCN2 with MTHFR and BHMT when methylation support looks uneven.
  • Use biomarker confirmation before escalating supplementation strategy.

Upload your DNA file and receive a structured metabolic pathway analysis with prioritized insights and suggested validation markers.

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Related pages

MTHFR

MTHFR gene metabolism

BHMT

BHMT gene function

Holotranscobalamin

holotranscobalamin and B12 transport

Homocysteine

homocysteine and methylation

B12 transport and recycling pathway

B12 transport and recycling pathway

Methylation pathway

methylation pathway explained

Is DNA metabolism analysis worth it?

is DNA metabolism analysis worth it

DNA nutrition analysis report

DNA nutrition analysis report

Related symptom angle

Low energy metabolism causes

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