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Primary topic: CUBN B12 absorption gene

CUBN Gene and Metabolism: What It Means for Your Body

CUBN matters when B12 availability may be limited before transport and recycling even begin.

What is the CUBN gene?

CUBN helps absorb vitamin B12 in the intestine, making it an upstream availability gene rather than a tissue-delivery gene.

How CUBN affects metabolism

If CUBN-related absorption is weaker, B12 support can look inconsistent even before transport and recycling questions are considered.

What happens when CUBN is altered

Altered CUBN function does not diagnose malabsorption, but it raises the value of checking functional B12 markers when symptoms and intake do not match.

Curated SNP evidence for CUBN

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

Evidence-backed report connection

CUBN currently has 2 curated SNPs, 9 claim-level scores, and 0 claims eligible for pathway scoring.

Open the sample report
rs12766939CUBN supporting signal6 claims · 12 study rows

unknown · AA

CUBN unscored target

Not used for pathway scoring

rs12766939 AA has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.

unknown · AC

CUBN unscored target

Not used for pathway scoring

rs12766939 AC has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.

unknown · AG

CUBN unscored target

Not used for pathway scoring

rs12766939 AG has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.

unknown · CC

CUBN unscored target

Not used for pathway scoring

rs12766939 CC has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.

unknown · CG

CUBN unscored target

Not used for pathway scoring

rs12766939 CG has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.

unknown · GG

CUBN unscored target

Not used for pathway scoring

rs12766939 GG has no scored directional claim for CUBN unscored target.

No reliable standalone end-user effect is assigned for CUBN rs12766939. All listed genotypes are treated as neutral in this simplified file.

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 places rs12766939 in an intronic CUBN annotation and lists A, C, and G genomic alleles. The record does not provide a clinical annotation or a direct functional consequence that would support assigning a standalone direction for CUBN activity or expression.PMC5801754review · close proxyA review of vitamin B12-related genetic polymorphisms describes CUBN as one of the genes studied for vitamin B12 status. Because this source does not establish a specific rs12766939 genotype effect, this simplified file keeps rs12766939 neutral rather than using it as a vitamin B12 prediction.
rs1801222CUBN supporting signal3 claims · 6 study rows

biomarker tendency · AA

CUBN biomarker tendency

Not used for pathway scoring

rs1801222 AA is associated with reduced CUBN biomarker tendency.

CUBN rs1801222 is scored as a tendency toward lower vitamin B12 status or higher B12-deficiency susceptibility for A-containing genotypes, strongest for AA.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data place rs1801222 in CUBN, the cubilin gene. Cubilin is relevant to vitamin B12 handling because it is part of the receptor system for intestinal uptake of intrinsic-factor-bound vitamin B12.Evidence 2gwas · close proxyA 2026 Diabetologia genome-wide association study identified CUBN rs1801222 as associated with metformin-induced vitamin B12 deficiency. Compared with GG, AG and AA had higher risk, with stronger and earlier risk in AA; the same article notes lower but still present genotype associations outside metformin exposure.

biomarker tendency · AG

CUBN biomarker tendency

Not used for pathway scoring

rs1801222 AG is associated with reduced CUBN biomarker tendency.

CUBN rs1801222 is scored as a tendency toward lower vitamin B12 status or higher B12-deficiency susceptibility for A-containing genotypes, strongest for AA.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data place rs1801222 in CUBN, the cubilin gene. Cubilin is relevant to vitamin B12 handling because it is part of the receptor system for intestinal uptake of intrinsic-factor-bound vitamin B12.Evidence 2gwas · close proxyA 2026 Diabetologia genome-wide association study identified CUBN rs1801222 as associated with metformin-induced vitamin B12 deficiency. Compared with GG, AG and AA had higher risk, with stronger and earlier risk in AA; the same article notes lower but still present genotype associations outside metformin exposure.

biomarker tendency · GG

CUBN biomarker tendency

Not used for pathway scoring

rs1801222 GG has no scored directional claim for CUBN biomarker tendency.

CUBN rs1801222 is scored as a tendency toward lower vitamin B12 status or higher B12-deficiency susceptibility for A-containing genotypes, strongest for AA.

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 place rs1801222 in CUBN, the cubilin gene. Cubilin is relevant to vitamin B12 handling because it is part of the receptor system for intestinal uptake of intrinsic-factor-bound vitamin B12.Evidence 2gwas · close proxyA 2026 Diabetologia genome-wide association study identified CUBN rs1801222 as associated with metformin-induced vitamin B12 deficiency. Compared with GG, AG and AA had higher risk, with stronger and earlier risk in AA; the same article notes lower but still present genotype associations outside metformin exposure.

Common symptoms people report

  • fatigue with unclear B12 context
  • brain fog despite intake that seems adequate
  • uncertainty around whether absorption is part of the B12 picture

Biomarkers to validate

Vitamin B12 context

Useful first-pass availability marker.

Methylmalonic acid

Adds functional B12 context.

Holotranscobalamin

Helps compare absorption and transport questions.

Where DNA analysis helps

DNA helps decide whether upstream B12 absorption deserves attention instead of assuming transport or methylation is the only issue.

Example Insight

Your B12 pathway may deserve upstream follow-up when intake alone does not explain the pattern.

Suggested validation: methylmalonic acid plus holotranscobalamin.

What to do next

  • Use methylmalonic acid and holotranscobalamin before assuming CUBN is active in practice.
  • Review CUBN together with TCN2 and MTRR for a fuller B12-support picture.
  • Treat the gene as a prompt for validation rather than diagnosis.

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

Get My DNA Report

Related pages

TCN2

TCN2 B12 transport gene

MTRR

MTRR B12 recycling gene

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

Why supplements do not work for me

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