Gene: MTHFR

Alternate names for this Gene: -

Gene Summary: The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.

Gene is located in Chromosome: 1

Location in Chromosome : 1p36.22

Description of this Gene: methylenetetrahydrofolate reductase

Type of Gene: protein-coding

rs17375901 in MTHFR gene and Atrial Fibrillation PMID 19597492 2009 Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.

rs17367504 in MTHFR gene and Birth Weight PMID 31043758 2019 Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

rs1476413 in MTHFR gene and Blood Pressure PMID 22100073 2011 Blood pressure loci identified with a gene-centric array.

PMID 21378095 2011 Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

PMID 21909110 2011 Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

rs17037390 in MTHFR gene and Coronary Artery Disease PMID 29212778 2018 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

rs17367504 in MTHFR gene and Coronary heart disease PMID 21347282 2011 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

rs13306556 in MTHFR gene and Diastolic blood pressure PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

PMID 27618452 2016 The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

PMID 29455858 2018 A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

PMID 29615537 2018 Strong impact of natural-selection-free heterogeneity in genetics of age-related phenotypes.

PMID 28739976 2017 Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

rs13306556 in MTHFR gene and Diastolic blood pressure measurement PMID 29912962 2018 Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

rs45553335 in MTHFR gene and Finding of Mean Corpuscular Hemoglobin PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1801133 in MTHFR gene and Folic acid measurement PMID 30339177 2018 The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) variant was the major genetic modifier of all 3 folate-related biomarkers in this Irish population and reached genome-wide significance for red blood cell folate (P = 1.37 × 10-17), serum folate (P = 2.82 × 10-11), and plasma total homocysteine (P = 1.26 × 10-19) concentrations.

PMID 29953918 2018 We validated that rs1801133 in MTHFR was significantly involved in serum folate (P = 4.21 × 10<sup>-19</sup>).

rs1057519359 in MTHFR gene and HOMOCYSTINURIA DUE TO DEFICIENCY OF N(5,10)-METHYLENETETRAHYDROFOLATE REDUCTASE ACTIVITY PMID 25856670 2016 Outcomes of four patients with homocysteine remethylation disorders detected by newborn screening.

PMID 26872964 2016 Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency.

PMID 15048559 2004 Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.

PMID 20490923 2011 Isolated remethylation disorders: do our treatments benefit patients?

PMID 25818041 2015 Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

PMID 9781030 1998 Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency.

PMID 8940272 1996 Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR.

PMID 7726158 1995 Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency.

PMID 10679944 2000 Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria.

PMID 20236116 2010 Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency.

PMID 25736335 2015 Insights into severe 5,10-methylenetetrahydrofolate reductase deficiency: molecular genetic and enzymatic characterization of 76 patients.

PMID 12673793 2003 Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation.

PMID 17409006 2007 Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.

PMID 24797679 2014 Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia.

PMID 27743313 2017 Functional characterization of missense mutations in severe methylenetetrahydrofolate reductase deficiency using a human expression system.

PMID 10551815 1999 Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae.

PMID 24997712 2014 Reversal of respiratory failure in both neonatal and late onset isolated remethylation disorders.

PMID 26898294 2016 Treatment with Mefolinate (5-Methyltetrahydrofolate), but Not Folic Acid or Folinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency.

PMID 22887477 2013 Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects.

rs1801133 in MTHFR gene and Homocysteine measurement PMID 20031578 2009 Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study.

PMID 23696881 2013 Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation.

PMID 30339177 2018 The 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) variant was the major genetic modifier of all 3 folate-related biomarkers in this Irish population and reached genome-wide significance for red blood cell folate (P = 1.37 × 10-17), serum folate (P = 2.82 × 10-11), and plasma total homocysteine (P = 1.26 × 10-19) concentrations.

PMID 23824729 2013 Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.

rs17367504 in MTHFR gene and Mean blood pressure PMID 27618448 2016 Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

PMID 21909110 2011 Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

rs9651118 in MTHFR gene and Moyamoya Disease PMID 29273593 2018 Two novel SNPs in genes regulating homocysteine metabolism, rs9651118 in <i>MTHFR</i> (<i>P</i><sub>combined</sub>=2.49×10<sup>-19</sup>; odds ratio, 0.65) and rs117353193 in <i>TCN2</i> (<i>P</i><sub>combined</sub>=6.15×10<sup>-13</sup>; odds ratio, 1.43), were associated with high-serum homocysteine in MMD cases.

rs9651118 in MTHFR gene and Moyamoya disease 1 PMID 29273593 2018 Two novel SNPs in genes regulating homocysteine metabolism, rs9651118 in <i>MTHFR</i> (<i>P</i><sub>combined</sub>=2.49×10<sup>-19</sup>; odds ratio, 0.65) and rs117353193 in <i>TCN2</i> (<i>P</i><sub>combined</sub>=6.15×10<sup>-13</sup>; odds ratio, 1.43), were associated with high-serum homocysteine in MMD cases.

rs1801133 in MTHFR gene and RDW - Red blood cell distribution width result PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs17037388 in MTHFR gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1801133 in MTHFR gene and Red cell distribution width determination PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1801133 in MTHFR gene and Schizophrenia PMID 22037552 2011 Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2.

rs17037390 in MTHFR gene and Systolic Pressure PMID 27618452 2016 The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.

PMID 29455858 2018 A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

PMID 27618447 2016 Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

PMID 19430483 2009 Genome-wide association study identifies eight loci associated with blood pressure.

PMID 28739976 2017 Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

rs17367504 in MTHFR gene and Systolic blood pressure measurement PMID 19430483 2009 Genome-wide association study identifies eight loci associated with blood pressure.

PMID 21909115 2011 Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

rs1801133 in MTHFR gene and VITAMIN B12 MEASUREMENT PMID 19303062 2009 Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.