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From SNPedia

Geno Mag Summary
(A;A) 0 most common genotype
(A;C) 2.1 Possibly impaired folate metabolism
(C;C) 2.5 Number of risks. Complex.
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (classic)rs1801131
1000 genomesrs1801131
GWAS Ctlgrs1801131
Max Magnitude2.5
? (A;A) (A;C) (C;C) 28

rs1801131 is a SNP in the MTHFR gene, representing an A>C mutation at mRNA position 1298, resulting in a glu429-to-ala (E429A) substitution (hence this SNP is also known as A1298C or E429A).

A diplotype (according to the authors, but perhaps actually a genoset) of rs1801131 and rs1801133 has been linked to slightly increased risk for several types of brain cancer. The highest risk of meningioma was associated with heterozygosity for both MTHFR SNPs (odds ratio 2.11, CI: 1.42-3.12, p=0.002). The corresponding odds ratio for glioma was 1.23 (CI: 0.91-1.66, p=0.02. In general, risks were increased with genotypes associated with reduced MTHFR activity.[PMID 18483342]


[PMID 19336565] Folate Intake, Methylenetetrahydrofolate Reductase Polymorphisms, and Breast Cancer Risk in Women from the Malmo Diet and Cancer Cohort.

[PMID 19465420] MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

[PMID 19746410] Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and age of onset in schizophrenia

[PMID 19759169] Increased breast cancer risk at high plasma folate concentrations among women with the MTHFR 677T allele

[PMID 20056627OA-icon.png] Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry

[PMID 20523222] MTHFR genotype and differential evolution of metabolic parameters after initiation of a second generation antipsychotic: an observational study

[PMID 20817226OA-icon.png] MTHFR polymorphisms in relation to ovarian cancer risk

[PMID 20863444] Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis

[PMID 20944139] Significant Association of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms with Prostate Cancer Susceptibility in Taiwan

[PMID 21125565] Folate pathway and nonsyndromic cleft lip and palate

[PMID 21254359OA-icon.png] Folate pathway and nonsyndromic cleft lip and palate

[PMID 21302350] rs1801131 shows no consistent association with schizophrenia overall in 12 studies totaling 3,000+ patients

[PMID 21567207] Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease

[PMID 22015309] MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer's and vascular dementia and their epistatic interaction

[PMID 22041626] [Association of methylenetetrahydrofolate reductase A1298C polymorphisms with non-syndromic cleft lip with or without cleft palate]

[PMID 22044028] The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population

[PMID 22116453OA-icon.png] Folate and vitamin B12-related genes and risk for omphalocele

[PMID 22144047OA-icon.png] A single-nucleotide polymorphism in the MTHFR (methylene tetrahydrofolate reductase) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy

[PMID 22283972OA-icon.png] C677T and A1298C Polymorphisms of MTHFR Gene and Their Relation to Homocysteine Levels in Turner Syndrome

[PMID 22707612OA-icon.png] Genetic Risk Factors for Thrombosis in Systemic Lupus Erythematosus

[PMID 11781870OA-icon.png] The frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans.

[PMID 14724163OA-icon.png] Analysis of candidate modifier loci for the severity of colonic familial adenomatous polyposis, with evidence for the importance of the N-acetyl transferases.

[PMID 16372906OA-icon.png] Failure to confirm influence of methyltetrahydrofolate reductase (MTHFR) polymorphisms on age at onset of Huntington disease.

[PMID 16642433OA-icon.png] Polymorphism in maternal LRP8 gene is associated with fetal growth.

[PMID 17035141OA-icon.png] Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.

[PMID 17119116OA-icon.png] Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.

[PMID 17301261] Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women.

[PMID 17659576OA-icon.png] Genetic polymorphisms in the methylenetetrahydrofolate reductase and thymidylate synthase genes and risk of hepatocellular carcinoma.

[PMID 17697348OA-icon.png] Technology to accelerate pangenomic scanning for unknown point mutations in exonic sequences: cycling temperature capillary electrophoresis (CTCE).

[PMID 18098291] Folate metabolism genes, vegetable intake and renal cancer risk in central Europe.

[PMID 18182569OA-icon.png] Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group.

[PMID 18191955OA-icon.png] Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.

[PMID 18199722] Dietary vitamin B6 intake and the risk of colorectal cancer.

[PMID 18203168OA-icon.png] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.

[PMID 18339682OA-icon.png] Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia.

[PMID 18521744OA-icon.png] BRCA1 promoter methylation is associated with increased mortality among women with breast cancer.

[PMID 18538037OA-icon.png] A simple and accurate SNP scoring strategy based on typeIIS restriction endonuclease cleavage and matrix-assisted laser desorption/ionization mass spectrometry.

[PMID 18547414OA-icon.png] Genotyping panel for assessing response to cancer chemotherapy.

[PMID 18603647OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18661527OA-icon.png] Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.

[PMID 18669903OA-icon.png] Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study.

[PMID 18708404OA-icon.png] B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.

[PMID 18708408OA-icon.png] Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.

[PMID 18715757OA-icon.png] Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.

[PMID 18813964OA-icon.png] Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta.

[PMID 18842806OA-icon.png] Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.

[PMID 18922824OA-icon.png] Genetic susceptibility to childhood leukaemia.

[PMID 18936436OA-icon.png] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

[PMID 18992148OA-icon.png] Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study.

[PMID 19048631OA-icon.png] Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.

[PMID 19062539] [Genetic diversity and the structure of linkage disequilibrium in the methylenetetrahydrofolate reductase locus].

[PMID 19064578OA-icon.png] No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk.

[PMID 19112534OA-icon.png] Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.

[PMID 19190136OA-icon.png] Association of thymidylate synthase gene with endometrial cancer risk in a Chinese population.

[PMID 19193698OA-icon.png] Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.

[PMID 19272686] Effect of the MTHFR C677T and A1298C polymorphisms on survival in patients with advanced CKD and ESRD: a prospective study.

[PMID 19336559OA-icon.png] Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.

[PMID 19376481OA-icon.png] One-carbon metabolism and breast cancer: an epidemiological perspective.

[PMID 19421414OA-icon.png] Genetic variation in the methylenetetrahydrofolate reductase gene, MTHFR, does not alter the risk of visual failure in Leber's hereditary optic neuropathy.

[PMID 19427845] Diagnostic method validation: High resolution melting (HRM) of small amplicons genotyping for the most common variants in the MTHFR gene.

[PMID 19493349OA-icon.png] 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.

[PMID 19538716OA-icon.png] Thrombotic genetic risk factors and warfarin pharmacogenetic variants in Sao Miguel's healthy population (Azores).

[PMID 19591822] Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.

[PMID 19657388OA-icon.png] Lack of association between genetic polymorphisms in enzymes associated with folate metabolism and unexplained reduced sperm counts.

[PMID 19700502] Synopsis and synthesis of candidate-gene association studies in chronic lymphocytic leukemia: the CUMAGAS-CLL information system.

[PMID 19706843OA-icon.png] Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk.

[PMID 19706844] Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.

[PMID 19760026] The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women.

[PMID 19776626OA-icon.png] Polymorphisms in methionine synthase, methionine synthase reductase and serine hydroxymethyltransferase, folate and alcohol intake, and colon cancer risk.

[PMID 19936946OA-icon.png] Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer.

[PMID 20065319] Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.

[PMID 20078877OA-icon.png] Gene polymorphisms in association with emerging cardiovascular risk markers in adult women.

[PMID 20111745OA-icon.png] Gene-gene interactions in the folate metabolic pathway and the risk of conotruncal heart defects.

[PMID 20472929] Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis.

[PMID 20692813] Gene-wide association study between the methylenetetrahydrofolate reductase gene (MTHFR) and schizophrenia in the Japanese population, with an updated meta-analysis on currently available data.

[PMID 20962791] Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants.

[PMID 21211571] MTHFR and MTRR genotype and haplotype analysis and colorectal cancer susceptibility in a case-control study from the Czech Republic.

[PMID 21255267] MTHFR polymorphisms and cognitive ageing in the ninth decade: the Lothian Birth Cohort 1921.

[PMID 21343546OA-icon.png] Phase II trial of pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer.

[PMID 21347786] DNA repair gene and MTHFR gene polymorphisms as prognostic markers in locally advanced adenocarcinoma of the esophagus or stomach treated with cisplatin and 5-fluorouracil-based neoadjuvant chemotherapy.

[PMID 21362212] [Detection of single nucleotide polymorphisms of mthfr and dpyd genes in leukemia cell lines K562 and K562/A02].

[PMID 21461582] Lack of association between methylenetetrahydrofolate reductase genetic polymorphisms and postmenopausal breast cancer risk.

[PMID 21819229] Methylenetetrahydrofolate reductase gene polymorphisms in Turkish children with attention-deficit/hyperactivity disorder.

[PMID 21931346] MTHFR gene polymorphisms and outcome of methotrexate treatment in patients with rheumatoid arthritis: analysis of key polymorphisms and meta-analysis of C677T and A1298C polymorphisms.

[PMID 22175540] Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with male infertility: a meta-analysis.

[PMID 22495907OA-icon.png] Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects.

[PMID 22540831] Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

[PMID 22833659OA-icon.png] Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2, CETP, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults

[PMID 23391848] OLR1 , PON1 and MTHFR Gene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population

[PMID 22957669OA-icon.png] Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA

[PMID 23652803] Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity and outcome in childhood acute lymphoblastic leukemia

[PMID 23450474] [Influence of methylenetetrahydrofolate reductase gene polymorphisms on antidepressant response]

Risk Rs1801131(C;C)
Alt Rs1801131(C;C)
Reference Rs1801131(A;A)
Significance Other
Disease MTHFR deficiency Schizophrenia Gastrointestinal stromal tumor not provided fluorouracil Neural tube defects not specified
Variation info
CLNDBN MTHFR deficiency, thermolabile type Schizophrenia, susceptibility to Gastrointestinal stromal tumor not provided fluorouracil, leucovorin, and oxaliplatin response - Efficacy Neural tube defects, folate-sensitive not specified
Reversed 1
HGVS NC_000001.10:g.11854476T>G
CLNSRC HGMD OMIM Allelic Variant PharmGKB Clinical Annotation UniProtKB (protein)
CLNACC RCV000003698.3, RCV000003699.3, RCV000144922.1, RCV000153515.4, RCV000211350.1, RCV000350590.1, RCV000430863.1,

[PMID 23401104] Folate-genetics and colorectal neoplasia: what we know and need to know next

[PMID 24380661] MTHFR C677T and A1298C polymorphisms and risk of nonsyndromic orofacial clefts in a south Indian population

[PMID 23484733] Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease

[PMID 22021659OA-icon.png] Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.

[PMID 22052259OA-icon.png] MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung.

[PMID 22706675] Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).

[PMID 22847291] Population distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C risk alleles for methotrexate toxicity in Israel.

[PMID 22890010] Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

[PMID 22903727OA-icon.png] Maternal and infant gene-folate interactions and the risk of neural tube defects.

[PMID 23175176OA-icon.png] Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.

[PMID 25075036] Evaluation of the Contribution of Methylenetetrahydrofolate Reductase Genotypes to Taiwan Breast Cancer

[PMID 25074646] Associations of Common Variants in Methionine Metabolism Pathway Genes with Plasma Homocysteine and the Risk of Type 2 Diabetes in Han Chinese

[PMID 24274352] Green tea consumption and breast cancer risk in Japanese women: a case-control study

[PMID 25246760OA-icon.png] Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma

[PMID 24959828OA-icon.png] Genetic association study with metabolic syndrome and metabolic-related traits in a cross-sectional sample and a 10-year longitudinal sample of chinese elderly population

[PMID 25808365] rs1801133C>T polymorphism in MTHFR is a risk factor for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

[PMID 26196053] Association between genetic polymorphisms in folate-related enzyme genes and infertile men with non-obstructive azoospermia

[PMID 26231489] Current Progress in Sports Genomics

[PMID 25566964] Polymorphisms in the MTHFR gene are associated with breast cancer risk and prognosis in a Chinese population

[PMID 25520092] Lack of association between polymorphisms in genes MTHFR and MDR1 with risk of childhood acute lymphoblastic leukemia

[PMID 26314858] Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy

[PMID 26336903] Impact of MTHFR rs1801133, MTHFR rs1801131 and ABCB1 rs1045642 polymorphisms with increased susceptibility of rheumatoid arthritis in the West Algerian population: A case-control study

[PMID 24967710OA-icon.png] Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study

[PMID 26522108] Methylenetetrahydrofolate reductase gene polymorphism in endometrial cancer: A systematic review and meta-analysis

[PMID 26689687OA-icon.png] Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis.

[PMID 26862484OA-icon.png] Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation.

[PMID 28405167OA-icon.png] Genetic variants and increased risk of meningioma: an updated meta-analysis.

[PMID 28700981] Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults.

[PMID 28915669OA-icon.png] Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults.

[PMID 29369772] Polymorphisms in folate metabolism genes are associated with susceptibility to presbycusis.

[PMID 29544444OA-icon.png] Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

[PMID 29600437] CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani children.

[PMID 30084051] Interaction of MTHFR gene with smoking and alcohol use and haplotype combination susceptibility to psoriasis in Chinese population.

[PMID 30843750] Genetic variants linked to folliculogenesis and successful pregnancy are not associated with twin births in a twins' town.

[PMID 31115963] The implication of single-nucleotide polymorphisms in ovarian hyperstimulation syndrome.

[PMID 31418317] Association study of high-frequency variants of MTHFR gene with retinal vein occlusion in a Spanish population.

[PMID 31539757] The role of single-nucleotide polymorphism (SNPs) in toxicity of induction chemotherapy based on cisplatin and paclitaxel in patients with advanced head and neck cancer.

[PMID 32117640OA-icon.png] Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease.

[PMID 33387129] Association of C677T (rs1081133) and A1298C (rs1801131) Methylenetetrahydrofolate Reductase Variants with Breast Cancer Susceptibility Among Asians: A Systematic Review and Meta-Analysis.