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Primary topic: CBS gene methylation

CBS Gene and Metabolism: What It Means for Your Body

CBS sits at the point where homocysteine can move out of remethylation and into the transsulfuration pathway, linking methylation balance with sulfur metabolism.

What is the CBS gene?

CBS helps direct homocysteine toward cystathionine and downstream sulfur metabolism. This is a routing decision inside the broader methylation network, which is why CBS is relevant when methylation and sulfur handling are discussed together.

How CBS affects metabolism

If CBS-related routing differs from expected, it can change how efficiently homocysteine is recycled versus moved downstream. That can affect methylation balance, sulfur-metabolite load, and how other methylation genes compensate.

What happens when CBS is altered

The practical issue is not whether CBS is active in a general sense, but whether its routing effect changes the broader methylation picture enough to show up in markers or symptoms.

Curated SNP evidence for CBS

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.

Methylation Sulfur / transsulfuration

Evidence-backed report connection

CBS currently has 7 curated SNPs, 13 claim-level scores, and 4 claims eligible for pathway scoring.

Open the sample report
rs121964962CBS c.919G>A / Gly307Ser1 claims · 3 study rows

enzyme activity · TT or compound-heterozygous CBS deficiency context

CBS transsulfuration activity tendency

Strong

rs121964962 T on the genomic plus strand, corresponding to CBS c.919G>A / p.Gly307Ser, is associated with lower cystathionine beta-synthase activity and reduced homocysteine-to-cystathionine transsulfuration flux in recessive or compound-heterozygous deficiency contexts.

CBS rs121964962 T is staged as a recessive pathogenic CBS deficiency allele relevant to sulfur / transsulfuration scoring.

Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 117clinical curation · directClinVar maps rs121964962 to CBS c.919G>A / p.Gly307Ser, classifies it as pathogenic for homocystinuria, and includes submitter evidence that homozygous or compound-heterozygous affected individuals have absent or near-absent CBS enzyme activity.GeneReviews CBS deficiencyclinical curation · directGeneReviews supports CBS deficiency as autosomal recessive homocystinuria, with diagnosis by biallelic CBS pathogenic variants and monitoring by plasma total homocysteine, methionine, and amino-acid markers.PMCID PMC7560719clinical curation · directThe checked classical homocystinuria cohort source describes CBS as catalyzing homocysteine plus serine to cystathionine, with CBS deficiency producing high homocysteine and methionine and low cystathionine and cysteine; it identifies G307S as a recurrent global CBS deficiency allele.
rs1801181CBS supporting signal3 claims · 9 study rows

unknown · AA

CBS unscored target

Not used for pathway scoring

rs1801181 AA has no scored directional claim for CBS unscored target.

CBS rs1801181 is treated as an unknown-effect synonymous variant, with no scored genotype direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordclinical curation · close proxyClinVar identifies rs1801181 as CBS NM_000071.3:c.1080C>T, a synonymous p.Ala360= variant, and lists the variant as benign for submitted clinical disease contexts. This supports avoiding disease-risk or enzyme-deficiency interpretation from this SNP alone.PMC2610294biomarker association · loose proxyA pseudoexfoliation syndrome and glaucoma study genotyped rs1801181 as a CBS A360A marker among homocysteine-metabolism genes. The study reported that none of the tested SNPs were significantly associated after multiple-comparison correction, so it does not support a practical genotype-effect direction for this SNP.PubMed 18098291other · loose proxyA renal cancer study analyzed common folate-metabolism variants including CBS Ex13+41C>T, rs1801181. The abstract emphasizes findings for MTHFR and TYMS rather than a clear CBS rs1801181 effect, which supports leaving the target as unknown for end-user interpretation.

unknown · AG

CBS unscored target

Not used for pathway scoring

rs1801181 AG has no scored directional claim for CBS unscored target.

CBS rs1801181 is treated as an unknown-effect synonymous variant, with no scored genotype direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordclinical curation · close proxyClinVar identifies rs1801181 as CBS NM_000071.3:c.1080C>T, a synonymous p.Ala360= variant, and lists the variant as benign for submitted clinical disease contexts. This supports avoiding disease-risk or enzyme-deficiency interpretation from this SNP alone.PMC2610294biomarker association · loose proxyA pseudoexfoliation syndrome and glaucoma study genotyped rs1801181 as a CBS A360A marker among homocysteine-metabolism genes. The study reported that none of the tested SNPs were significantly associated after multiple-comparison correction, so it does not support a practical genotype-effect direction for this SNP.PubMed 18098291other · loose proxyA renal cancer study analyzed common folate-metabolism variants including CBS Ex13+41C>T, rs1801181. The abstract emphasizes findings for MTHFR and TYMS rather than a clear CBS rs1801181 effect, which supports leaving the target as unknown for end-user interpretation.

unknown · GG

CBS unscored target

Not used for pathway scoring

rs1801181 GG has no scored directional claim for CBS unscored target.

CBS rs1801181 is treated as an unknown-effect synonymous variant, with no scored genotype direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordclinical curation · close proxyClinVar identifies rs1801181 as CBS NM_000071.3:c.1080C>T, a synonymous p.Ala360= variant, and lists the variant as benign for submitted clinical disease contexts. This supports avoiding disease-risk or enzyme-deficiency interpretation from this SNP alone.PMC2610294biomarker association · loose proxyA pseudoexfoliation syndrome and glaucoma study genotyped rs1801181 as a CBS A360A marker among homocysteine-metabolism genes. The study reported that none of the tested SNPs were significantly associated after multiple-comparison correction, so it does not support a practical genotype-effect direction for this SNP.PubMed 18098291other · loose proxyA renal cancer study analyzed common folate-metabolism variants including CBS Ex13+41C>T, rs1801181. The abstract emphasizes findings for MTHFR and TYMS rather than a clear CBS rs1801181 effect, which supports leaving the target as unknown for end-user interpretation.
rs234706CBS C699T3 claims · 12 study rows

biomarker tendency · AA

CBS biomarker tendency

Not used for pathway scoring

rs234706 AA is associated with reduced CBS biomarker tendency.

CBS rs234706 is scored as a modest tendency toward lower homocysteine-related biomarker levels for A-containing genotypes, strongest for AA.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordclinical curation · close proxyClinVar identifies rs234706 as CBS c.699C>T, a synonymous p.Tyr233= variant, and lists benign clinical submissions. This does not itself support a lower homocysteine biomarker tendency.PubMed 11149614biomarker association · close proxyAras et al. studied CBS 699C>T and 1080C>T in 1,055 people. In the abstract, people with one or two copies of the 699T allele had lower post-methionine-load total homocysteine than people with the 699CC genotype, with the strongest result reported for 699TT. This supports a modest lower-homocysteine tendency for A-containing genotypes.PubMed 10833331biomarker association · close proxyKruger et al. reported that CBS 699C>T and 1080T>C were associated with stronger total homocysteine lowering after folic acid supplementation, and that 699T homozygotes had a larger average lowering than 699C homozygotes. The same abstract notes that these are synonymous changes and may reflect linkage with other CBS-region variation, so the effect should not be treated as a direct enzyme-activity measurement.Evidence 4biomarker association · close proxyThis European Journal of Human Genetics association study reported no association between the CBS genotypes studied and elevated fasting or post-load homocysteine, so it is treated as non-supporting evidence.

biomarker tendency · AG

CBS biomarker tendency

Not used for pathway scoring

rs234706 AG is associated with reduced CBS biomarker tendency.

CBS rs234706 is scored as a modest tendency toward lower homocysteine-related biomarker levels for A-containing genotypes, strongest for AA.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordclinical curation · close proxyClinVar identifies rs234706 as CBS c.699C>T, a synonymous p.Tyr233= variant, and lists benign clinical submissions. This does not itself support a lower homocysteine biomarker tendency.PubMed 11149614biomarker association · close proxyAras et al. studied CBS 699C>T and 1080C>T in 1,055 people. In the abstract, people with one or two copies of the 699T allele had lower post-methionine-load total homocysteine than people with the 699CC genotype, with the strongest result reported for 699TT. This supports a modest lower-homocysteine tendency for A-containing genotypes.PubMed 10833331biomarker association · close proxyKruger et al. reported that CBS 699C>T and 1080T>C were associated with stronger total homocysteine lowering after folic acid supplementation, and that 699T homozygotes had a larger average lowering than 699C homozygotes. The same abstract notes that these are synonymous changes and may reflect linkage with other CBS-region variation, so the effect should not be treated as a direct enzyme-activity measurement.Evidence 4biomarker association · close proxyThis European Journal of Human Genetics association study reported no association between the CBS genotypes studied and elevated fasting or post-load homocysteine, so it is treated as non-supporting evidence.

biomarker tendency · GG

CBS biomarker tendency

Not used for pathway scoring

rs234706 GG has no scored directional claim for CBS biomarker tendency.

CBS rs234706 is scored as a modest tendency toward lower homocysteine-related biomarker levels 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
ClinVar recordclinical curation · close proxyClinVar identifies rs234706 as CBS NM_000071.3:c.699C>T, a synonymous p.Tyr233= variant, and lists the variant as benign for submitted clinical disease contexts. This supports keeping the interpretation limited to a possible biomarker tendency rather than a disease-risk or enzyme-deficiency claim.PubMed 11149614biomarker association · close proxyAras et al. studied CBS 699C>T and 1080C>T in 1,055 people. In the abstract, people with one or two copies of the 699T allele had lower post-methionine-load total homocysteine than people with the 699CC genotype, with the strongest result reported for 699TT. This supports a modest lower-homocysteine tendency for A-containing genotypes.PubMed 10833331biomarker association · close proxyKruger et al. reported that CBS 699C>T and 1080T>C were associated with stronger total homocysteine lowering after folic acid supplementation, and that 699T homozygotes had a larger average lowering than 699C homozygotes. The same abstract notes that these are synonymous changes and may reflect linkage with other CBS-region variation, so the effect should not be treated as a direct enzyme-activity measurement.Evidence 4biomarker association · close proxyA separate European Journal of Human Genetics association study assessed CBS 699C>T, 1080C>T, and a repeat marker in arterial occlusive disease cases and controls. Its abstract reports no association between the CBS genotypes studied and elevated fasting or post-load homocysteine. This conflicting evidence lowers certainty.
rs234709CBS homocysteine supporting signal1 claims · 3 study rows

biomarker tendency · CT

Plasma total homocysteine tendency

Moderate

rs234709 CT carries one T allele near CBS and is associated with lower plasma total homocysteine tendency.

CBS rs234709 CT is staged as a modest lower-homocysteine biomarker genotype within methylation outflow 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 rs234709 as a chromosome 21 CBS-region variant. This row supports variant identity only and does not assign biomarker direction.PubMed 23824729gwas · directvan Meurs et al. reported rs234709 near CBS among known loci associated with plasma total homocysteine. The coded T allele frequency was 0.45, with beta -0.0718 SD per allele, SE 0.007, and P = 3.90e-24 for total homocysteine.GWAS Catalog association 34423gwas · directGWAS Catalog records rs234709-T for homocysteine measurement, mapped to CBS, with beta direction decrease, beta 0.0718, SE 0.007, and P = 4e-24. This supports the T allele as a lower-homocysteine biomarker allele.
rs2850144CBS supporting signal3 claims · 9 study rows

expression · GG

CBS gene expression

Not used for pathway scoring

rs2850144 GG is associated with increased CBS gene expression.

CBS rs2850144 is scored as a higher-expression tendency when the G allele is present, with the strongest score for GG.

Likely effectHigher gene expression signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs2850144 list CBS, cystathionine beta-synthase, as the annotated gene and C/G as the common alleles at this locus.PMC3567826expression eqtl · directZhao et al. described rs2850144 as the CBS promoter variant -4673C>G. In human cardiovascular tissue samples, CBS mRNA was higher in CG samples and highest in GG samples compared with CC samples. Reporter assays also showed higher promoter activity for the G allele. This supports scoring G-containing genotypes as a higher CBS expression tendency.PMC3567826biomarker association · directThe study reported no significant association between rs2850144 genotype and fasting plasma homocysteine in healthy young adults. This biomarker-null result is not scored for the CBS expression claim.

expression · CG

CBS gene expression

Not used for pathway scoring

rs2850144 CG is associated with increased CBS gene expression.

CBS rs2850144 is scored as a higher-expression tendency when the G allele is present, with the strongest score for GG.

Likely effectHigher gene expression signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs2850144 list CBS, cystathionine beta-synthase, as the annotated gene and C/G as the common alleles at this locus.PMC3567826expression eqtl · directZhao et al. described rs2850144 as the CBS promoter variant -4673C>G. In human cardiovascular tissue samples, CBS mRNA was higher in CG samples and highest in GG samples compared with CC samples. Reporter assays also showed higher promoter activity for the G allele. This supports scoring G-containing genotypes as a higher CBS expression tendency.PMC3567826biomarker association · directThe study reported no significant association between rs2850144 genotype and fasting plasma homocysteine in healthy young adults. This biomarker-null result is not scored for the CBS expression claim.

expression · CC

CBS gene expression

Not used for pathway scoring

rs2850144 CC has no scored directional claim for CBS gene expression.

CBS rs2850144 is scored as a higher-expression tendency when the G allele is present, with the strongest score for GG.

Likely effectNo clear expression signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs2850144 list CBS, cystathionine beta-synthase, as the annotated gene and C/G as the common alleles at this locus.PMC3567826expression eqtl · directZhao et al. described rs2850144 as the CBS promoter variant -4673C>G. In human cardiovascular tissue samples, CBS mRNA was higher in CG samples and highest in GG samples compared with CC samples. Reporter assays also showed higher promoter activity for the G allele. This supports scoring G-containing genotypes as a higher CBS expression tendency.PMC3567826biomarker association · directThe same study reported that rs2850144 genotype was not significantly associated with fasting plasma homocysteine in healthy young adults. This supports keeping the record focused on expression tendency rather than predicting a blood biomarker result.
rs28934891CBS c.1330G>A / Asp444Asn1 claims · 2 study rows

enzyme activity · TT or compound-heterozygous CBS deficiency context

CBS transsulfuration activity tendency

Strong

rs28934891 T (forward-genomic; CBS c.1330G>A / p.Asp444Asn transcript context) is associated with lower CBS transsulfuration activity tendency and homocysteine/methionine biomarker disruption in recessive or compound-heterozygous CBS deficiency contexts.

CBS rs28934891 T is staged as the forward-genomic rare pathogenic CBS deficiency allele affecting transsulfuration entry from homocysteine toward cystathionine.

Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar RCV000000149clinical curation · directClinVar maps rs28934891 to CBS c.1330G>A / p.Asp444Asn, reports observations in homocystinuria, and cites experimental studies showing that the missense change affects CBS function.GeneReviews CBS deficiencyclinical curation · directGeneReviews supports CBS deficiency as a transsulfuration disorder with biochemical monitoring centered on homocysteine, methionine, cystathionine, cysteine, and treatment responsiveness.
rs5742905CBS c.833T>C / Ile278Thr1 claims · 2 study rows

enzyme activity · GG

CBS transsulfuration activity tendency

Strong

rs5742905 GG, the genomic plus-strand representation of CBS c.833T>C / p.Ile278Thr, is associated with lower cystathionine beta-synthase activity and reduced homocysteine-to-cystathionine transsulfuration flux.

CBS rs5742905 G is staged as a recessive pathogenic CBS deficiency allele relevant to sulfur / transsulfuration scoring.

Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 120clinical curation · directClinVar maps rs5742905 to CBS c.833T>C / p.Ile278Thr, classifies the variant as pathogenic, and includes submitter evidence that the allele acts recessively in homocystinuria with reduced enzymatic activity evidence.GeneReviews CBS deficiencyclinical curation · directGeneReviews supports CBS deficiency as impaired transsulfuration in which CBS catalyzes homocysteine plus serine to cystathionine, with deficiency leading to homocysteine and methionine accumulation and low cysteine.

Common symptoms people report

  • concern about methylation instability
  • variable response to sulfur-containing supplements
  • brain fog or fatigue with unclear methylation context
  • confusion around homocysteine interpretation

Biomarkers to validate

Homocysteine

Core marker for understanding how the pathway balance is behaving.

Vitamin B6

Relevant cofactor context for transsulfuration.

Sulfate or sulfur-related follow-up where relevant

Adds context when sulfur handling seems clinically relevant.

Where DNA analysis helps

DNA helps determine whether CBS should be treated as part of a methylation-routing question. It is most useful when interpreted together with MTHFR, BHMT, and biomarker data.

Example Insight

Your methylation-routing pathway may be shifting homocysteine handling away from the expected balance.

Suggested validation: homocysteine and vitamin B6.

What to do next

  • Do not interpret CBS in isolation from the rest of methylation.
  • Validate homocysteine first before speculating about sulfur overflow.
  • Compare CBS with MTHFR and BHMT to understand pathway routing.

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

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