What this pathway does
The pathway helps convert choline into phosphatidylcholine and related compounds needed for membranes, lipid transport, and methylation-linked support.
Why it matters
It matters because some people have more friction around choline demand than generic nutrition advice suggests. That can affect lipid handling and how well supplement strategies land.
What creates pressure on this pathway
- lower endogenous phosphatidylcholine production
- overlap with methylation support demand
- dietary intake that does not match pathway needs
Validation markers to consider
- homocysteine context
- ApoB and triglycerides when lipid handling overlaps
- functional response tracking to nutrition changes
Genes and SNPs connected to this pathway
Choline is a nutrient found in foods like eggs, meat, fish, and soy. It helps the liver handle fat and supports brain and nerve function.
Study rows support the SNP/gene claim. The pathway connection comes from the curated gene-to-pathway map.
What may run higher
You may need more choline-rich food, like eggs, meat, fish, or soy.
What may work more slowly
Choline is less likely to be a major DNA-driven issue.
What to check next
Check choline-rich food intake, homocysteine, ALT, AST, GGT, triglycerides, and liver context.
4mapped genes
6mapped SNPs
21SNP/gene claims
10report eligible
PEMT2 SNPs - 6 claimsShow SNPs
Open gene pagers123258173 claims - 9 study rows
expression - CC
PEMT gene expression
rs12325817 CC is associated with reduced PEMT gene expression.
PEMT rs12325817 is scored as a lower hormone-responsive PEMT expression tendency for C-containing genotypes, strongest for CC.
Likely effectLower gene expression signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs12325817 as a PEMT variant with transcript annotations in or near PEMT regulatory regions. This supports curation against PEMT expression rather than a protein-coding enzyme-change score.PubMed 16816108biomarker association - loose proxyDa Costa et al. fed 57 people a low-choline diet and reported that 18 of 23 carriers of the PEMT -744C allele, rs12325817, developed organ dysfunction under that controlled low-choline challenge. This supports a C-allele tendency that matters most when dietary choline is limited.PubMed 21059658functional assay - directResseguie et al. reported that rs12325817 was strongly linked with choline deficiency syndrome in women and was near a critical estrogen response element. The risk allele failed to bind estrogen receptor or FOXA1 in their experiments, supporting lower hormone-inducible PEMT expression as the curated effect.
expression - CG
PEMT gene expression
rs12325817 CG is associated with reduced PEMT gene expression.
PEMT rs12325817 is scored as a lower hormone-responsive PEMT expression tendency for C-containing genotypes, strongest for CC.
Likely effectLower gene expression signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs12325817 as a PEMT variant with transcript annotations in or near PEMT regulatory regions. This supports curation against PEMT expression rather than a protein-coding enzyme-change score.PubMed 16816108biomarker association - loose proxyDa Costa et al. fed 57 people a low-choline diet and reported that 18 of 23 carriers of the PEMT -744C allele, rs12325817, developed organ dysfunction under that controlled low-choline challenge. This supports a C-allele tendency that matters most when dietary choline is limited.PubMed 21059658functional assay - directResseguie et al. reported that rs12325817 was strongly linked with choline deficiency syndrome in women and was near a critical estrogen response element. The risk allele failed to bind estrogen receptor or FOXA1 in their experiments, supporting lower hormone-inducible PEMT expression as the curated effect.
expression - GG
PEMT gene expression
rs12325817 GG has no scored directional claim for PEMT gene expression.
PEMT rs12325817 is scored as a lower hormone-responsive PEMT expression tendency for C-containing genotypes, strongest for CC.
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 identify rs12325817 as a PEMT variant with transcript annotations in or near PEMT regulatory regions. This supports curation against PEMT expression rather than a protein-coding enzyme-change score.PubMed 16816108biomarker association - loose proxyDa Costa et al. fed 57 people a low-choline diet and reported that 18 of 23 carriers of the PEMT -744C allele, rs12325817, developed organ dysfunction under that controlled low-choline challenge. This supports a C-allele tendency that matters most when dietary choline is limited.PubMed 21059658functional assay - directResseguie et al. reported that rs12325817 was strongly linked with choline deficiency syndrome in women and was near a critical estrogen response element. The risk allele failed to bind estrogen receptor or FOXA1 in their experiments, supporting lower hormone-inducible PEMT expression as the curated effect.
rs79463 claims - 12 study rows
enzyme activity - TT
PEMT enzyme activity
rs7946 TT is associated with reduced PEMT enzyme activity.
PEMT rs7946 is scored as a lower PEMT enzyme-activity tendency for T-containing genotypes, with a stronger score for TT than CT.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7946 as a C/T variant in PEMT. Transcript annotations include NM_007169.3:c.523G>A with a predicted p.Val175Met protein change for the T-containing genomic allele, supporting use of C, CT, and TT genotype letters in this file.PMC1256033functional assay - directSong et al. reported that the PEMT V175M variant showed diminished activity in transfected cells and was more common in people with nonalcoholic fatty liver disease than controls in their study. This supports scoring T-containing genotypes as a lower PEMT enzyme-activity tendency, with a larger score for TT than CT.PubMed 26636496review - directTan et al. performed a meta-analysis of PEMT rs7946 and nonalcoholic fatty liver disease and reported that the transcript A allele was associated with higher NAFLD susceptibility, especially in East Asian subgroup analyses. This supports biological relevance but is still disease-association evidence, so the JSON limits interpretation to enzyme-activity tendency rather than disease prediction.PubMed 16816108functional assay - directA controlled feeding study on choline requirement noted rs7946 as a functionally significant PEMT SNP, but also reported that the low-choline response was not explained by this SNP alone. This supports a conservative certainty score and highlights that diet, sex, hormones, and other variants can affect practical interpretation.
enzyme activity - CT
PEMT enzyme activity
rs7946 CT is associated with reduced PEMT enzyme activity.
PEMT rs7946 is scored as a lower PEMT enzyme-activity tendency for T-containing genotypes, with a stronger score for TT than CT.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7946 as a C/T variant in PEMT. Transcript annotations include NM_007169.3:c.523G>A with a predicted p.Val175Met protein change for the T-containing genomic allele, supporting use of C, CT, and TT genotype letters in this file.PMC1256033functional assay - directSong et al. reported that the PEMT V175M variant showed diminished activity in transfected cells and was more common in people with nonalcoholic fatty liver disease than controls in their study. This supports scoring T-containing genotypes as a lower PEMT enzyme-activity tendency, with a larger score for TT than CT.PubMed 26636496review - directTan et al. performed a meta-analysis of PEMT rs7946 and nonalcoholic fatty liver disease and reported that the transcript A allele was associated with higher NAFLD susceptibility, especially in East Asian subgroup analyses. This supports biological relevance but is still disease-association evidence, so the JSON limits interpretation to enzyme-activity tendency rather than disease prediction.PubMed 16816108functional assay - directA controlled feeding study on choline requirement noted rs7946 as a functionally significant PEMT SNP, but also reported that the low-choline response was not explained by this SNP alone. This supports a conservative certainty score and highlights that diet, sex, hormones, and other variants can affect practical interpretation.
enzyme activity - CC
PEMT enzyme activity
rs7946 CC has no scored directional claim for PEMT enzyme activity.
PEMT rs7946 is scored as a lower PEMT enzyme-activity tendency for T-containing genotypes, with a stronger score for TT than CT.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7946 as a C/T variant in PEMT. Transcript annotations include NM_007169.3:c.523G>A with a predicted p.Val175Met protein change for the T-containing genomic allele, supporting use of C, CT, and TT genotype letters in this file.PMC1256033functional assay - directSong et al. reported that the PEMT V175M variant showed diminished activity in transfected cells and was more common in people with nonalcoholic fatty liver disease than controls in their study. This supports scoring T-containing genotypes as a lower PEMT enzyme-activity tendency, with a larger score for TT than CT.PubMed 26636496review - directTan et al. performed a meta-analysis of PEMT rs7946 and nonalcoholic fatty liver disease and reported that the transcript A allele was associated with higher NAFLD susceptibility, especially in East Asian subgroup analyses. This supports biological relevance but is still disease-association evidence, so the JSON limits interpretation to enzyme-activity tendency rather than disease prediction.PubMed 16816108functional assay - directA controlled feeding study on choline requirement noted rs7946 as a functionally significant PEMT SNP, but also reported that the low-choline response was not explained by this SNP alone. This supports a conservative certainty score and highlights that diet, sex, hormones, and other variants can affect practical interpretation.
BCAM1 SNPs - 6 claimsShow SNPs
Open gene pagers38101416 claims - 12 study rows
expression - AA
BCAM gene expression
rs3810141 AA is associated with reduced BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
Likely effectLower gene expression signal
Signal sizeLarge signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
expression - AC
BCAM gene expression
rs3810141 AC is associated with reduced BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
Likely effectLower gene expression signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
expression - AT
BCAM gene expression
rs3810141 AT is associated with reduced BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
Likely effectLower gene expression signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
expression - CC
BCAM gene expression
rs3810141 CC has no scored directional claim for BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
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 place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
expression - CT
BCAM gene expression
rs3810141 CT has no scored directional claim for BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
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 place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
expression - TT
BCAM gene expression
rs3810141 TT has no scored directional claim for BCAM gene expression.
BCAM rs3810141 is scored as a reduced BCAM protein-expression tendency only for A-containing genotypes; common C/T genotypes are not scored as a clear effect in this simplified record.
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 place rs3810141 in BCAM, the basal cell adhesion molecule gene, and annotate the variant as stop gained in BCAM. The RefSNP record includes C, A, and T letters, so this file only scores A-containing calls as the loss-of-function side.ClinVar recordclinical curation - close proxyClinVar links rs3810141 to NM_005581.5(BCAM):c.711C>A, p.Cys237Ter, and the recessive Lutheran-null blood group phenotype. The submission description reports a healthy homozygous individual and heterozygous relatives, supporting a protein-loss interpretation without broad health-risk claims.
CHDH1 SNPs - 3 claimsShow SNPs
Open gene pagers126763 claims - 6 study rows
enzyme activity - AA
CHDH enzyme activity
rs12676 AA is associated with reduced CHDH enzyme activity.
CHDH rs12676 is scored as a lower choline dehydrogenase activity tendency for A-containing genotypes, strongest for AA and intermediate for AC.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs12676 in CHDH, the choline dehydrogenase gene, and annotate it as a coding missense variant. The common genotype letters represented here are A and C.PubMed 10functional assay - directJohnson and colleagues describe rs12676 as a functional CHDH coding variant. In their study, variant-side genotypes had lower sperm ATP concentrations and lower CHDH protein in sperm and hepatocytes, supporting a cautious lower CHDH activity tendency for A-containing genotypes in this file.
enzyme activity - AC
CHDH enzyme activity
rs12676 AC is associated with reduced CHDH enzyme activity.
CHDH rs12676 is scored as a lower choline dehydrogenase activity tendency for A-containing genotypes, strongest for AA and intermediate for AC.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs12676 in CHDH, the choline dehydrogenase gene, and annotate it as a coding missense variant. The common genotype letters represented here are A and C.PubMed 10functional assay - directJohnson and colleagues describe rs12676 as a functional CHDH coding variant. In their study, variant-side genotypes had lower sperm ATP concentrations and lower CHDH protein in sperm and hepatocytes, supporting a cautious lower CHDH activity tendency for A-containing genotypes in this file.
enzyme activity - CC
CHDH enzyme activity
rs12676 CC has no scored directional claim for CHDH enzyme activity.
CHDH rs12676 is scored as a lower choline dehydrogenase activity tendency for A-containing genotypes, strongest for AA and intermediate for AC.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs12676 in CHDH, the choline dehydrogenase gene, and annotate it as a coding missense variant. The common genotype letters represented here are A and C.PubMed 10functional assay - directJohnson and colleagues describe rs12676 as a functional CHDH coding variant. In their study, variant-side genotypes had lower sperm ATP concentrations and lower CHDH protein in sperm and hepatocytes, supporting a cautious lower CHDH activity tendency for A-containing genotypes in this file.
MTHFR2 SNPs - 6 claimsShow SNPs
Open gene pagers18011313 claims - 9 study rows
enzyme activity - GG
MTHFR enzyme activity
rs1801131 GG is associated with reduced MTHFR enzyme activity.
MTHFR rs1801131 is scored as a mild lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportLimited support
Report useIncluded in pathway scoring
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3521 identifies rs1801131 as MTHFR NM_005957.5:c.1286A>C, protein p.Glu429Ala, also named MTHFR 1298A-C / GLU429ALA. The canonical SPDI shown by ClinVar is NC_000001.11:11794418:T:G, so this file uses the dbSNP/GRCh38 forward-strand genotype letters T and G. ClinVar classifications for listed germline conditions are mostly benign or benign/likely benign, so this record is limited to enzyme-activity tendency.PubMed 9719624functional assay - directWeisberg et al. 1998 characterized MTHFR A1298C as an E-to-A substitution and reported that the polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. The abstract also reported lower activity in people heterozygous for both C677T and A1298C, but it does not give an equally direct single-heterozygote A1298C estimate, so GT is assigned a small magnitude and lower certainty.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
enzyme activity - GT
MTHFR enzyme activity
rs1801131 GT is associated with reduced MTHFR enzyme activity.
MTHFR rs1801131 is scored as a mild lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectLower enzyme activity signal
Signal sizeMinimal signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3521 identifies rs1801131 as MTHFR NM_005957.5:c.1286A>C, protein p.Glu429Ala, also named MTHFR 1298A-C / GLU429ALA. The canonical SPDI shown by ClinVar is NC_000001.11:11794418:T:G, so this file uses the dbSNP/GRCh38 forward-strand genotype letters T and G. ClinVar classifications for listed germline conditions are mostly benign or benign/likely benign, so this record is limited to enzyme-activity tendency.PubMed 9719624functional assay - directWeisberg et al. 1998 characterized MTHFR A1298C as an E-to-A substitution and reported that the polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. The abstract also reported lower activity in people heterozygous for both C677T and A1298C, but it does not give an equally direct single-heterozygote A1298C estimate, so GT is assigned a small magnitude and lower certainty.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
enzyme activity - TT
MTHFR enzyme activity
rs1801131 TT has no scored directional claim for MTHFR enzyme activity.
MTHFR rs1801131 is scored as a mild lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3521 identifies rs1801131 as MTHFR NM_005957.5:c.1286A>C, protein p.Glu429Ala, also named MTHFR 1298A-C / GLU429ALA. The canonical SPDI shown by ClinVar is NC_000001.11:11794418:T:G, so this file uses the dbSNP/GRCh38 forward-strand genotype letters T and G. ClinVar classifications for listed germline conditions are mostly benign or benign/likely benign, so this record is limited to enzyme-activity tendency.PubMed 9719624functional assay - directWeisberg et al. 1998 characterized MTHFR A1298C as an E-to-A substitution and reported that the polymorphism was associated with decreased enzyme activity; homozygotes had approximately 60% of control activity in lymphocytes. The abstract also reported lower activity in people heterozygous for both C677T and A1298C, but it does not give an equally direct single-heterozygote A1298C estimate, so GT is assigned a small magnitude and lower certainty.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
rs18011333 claims - 9 study rows
enzyme activity - AA
MTHFR enzyme activity
rs1801133 AA is associated with reduced MTHFR enzyme activity.
MTHFR rs1801133 is scored as a lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3520 identifies rs1801133 as MTHFR NM_005957.5:c.665C>T, protein p.Ala222Val, also named MTHFR 677C-T / ALA222VAL. The canonical SPDI shown by ClinVar is NC_000001.11:11796320:G:A, so this file uses the dbSNP/GRCh38 forward-strand genotype letters G and A. ClinVar condition classifications are mixed and include benign, uncertain, conflicting, and drug-response contexts, so this record is limited to enzyme-activity tendency rather than disease interpretation.PubMed 7647779functional assay - directFrosst et al. 1995 reported a common MTHFR mutation that changes a conserved amino acid. The PubMed abstract states that heterozygous or homozygous mutation status correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts, and that homozygous individuals had significantly elevated plasma homocysteine. This supports a negative enzyme-activity direction for A-containing genotypes, with a larger magnitude for AA than AG.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
enzyme activity - AG
MTHFR enzyme activity
rs1801133 AG is associated with reduced MTHFR enzyme activity.
MTHFR rs1801133 is scored as a lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3520 identifies rs1801133 as MTHFR NM_005957.5:c.665C>T, protein p.Ala222Val, also named MTHFR 677C-T / ALA222VAL. The canonical SPDI shown by ClinVar is NC_000001.11:11796320:G:A, so this file uses the dbSNP/GRCh38 forward-strand genotype letters G and A. ClinVar condition classifications are mixed and include benign, uncertain, conflicting, and drug-response contexts, so this record is limited to enzyme-activity tendency rather than disease interpretation.PubMed 7647779functional assay - directFrosst et al. 1995 reported a common MTHFR mutation that changes a conserved amino acid. The PubMed abstract states that heterozygous or homozygous mutation status correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts, and that homozygous individuals had significantly elevated plasma homocysteine. This supports a negative enzyme-activity direction for A-containing genotypes, with a larger magnitude for AA than AG.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
enzyme activity - GG
MTHFR enzyme activity
rs1801133 GG has no scored directional claim for MTHFR enzyme activity.
MTHFR rs1801133 is scored as a lower-activity tendency, with stronger scoring for the two-copy genotype than the one-copy genotype.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
ClinVar recordidentity only - unknownClinVar Variation ID 3520 identifies rs1801133 as MTHFR NM_005957.5:c.665C>T, protein p.Ala222Val, also named MTHFR 677C-T / ALA222VAL. The canonical SPDI shown by ClinVar is NC_000001.11:11796320:G:A, so this file uses the dbSNP/GRCh38 forward-strand genotype letters G and A. ClinVar condition classifications are mixed and include benign, uncertain, conflicting, and drug-response contexts, so this record is limited to enzyme-activity tendency rather than disease interpretation.PubMed 7647779functional assay - directFrosst et al. 1995 reported a common MTHFR mutation that changes a conserved amino acid. The PubMed abstract states that heterozygous or homozygous mutation status correlated with reduced enzyme activity and increased thermolability in lymphocyte extracts, and that homozygous individuals had significantly elevated plasma homocysteine. This supports a negative enzyme-activity direction for A-containing genotypes, with a larger magnitude for AA than AG.PubMed 23288205clinical curation - close proxyThe 2013 ACMG practice guideline says MTHFR polymorphism testing has minimal clinical utility in routine thrombophilia evaluation and discusses disproven or weak disease-risk associations. This supports conservative certainty and prevents using this genotype-effect row as a diagnosis, disease-risk estimate, or treatment rule.
Where DNA analysis helps
DNA helps decide whether choline-related follow-up deserves attention before broad nutrition or supplement changes are made blindly.
Example interpretation
Your choline pathway may deserve closer attention because nutrient demand and lipid-handling signals overlap.
Suggested validation: homocysteine plus lipid markers.
What to do next
- look at choline support in the context of methylation and lipids
- validate related biomarkers before escalating supplementation
- compare PEMT with methylation and lipid transport genes