Gene Symbol: MTHFD1
Description: methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1
Alias: CIMAH, MTHFC, MTHFD, C-1-tetrahydrofolate synthase, cytoplasmic, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase, C1-THF synthase, cytoplasmic C-1-tetrahydrofolate synthase, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
Species: human
Products:     MTHFD1

Top Publications

  1. Parle McDermott A, Pangilinan F, Mills J, Signore C, Molloy A, Cotter A, et al. A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod. 2005;11:477-80 pubmed
    ..The primary aim of this study was to test a polymorphism within the trifunctional folate enzyme MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-..
  2. Sun J, Xu Y, Zhu Y, Lu H. Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in Type 2 diabetes mellitus. J Endocrinol Invest. 2006;29:814-20 pubmed
    ..MTHFR C677T gene polymorphism associated with a predisposition to increased plasma homocysteine levels could constitute a useful predictive marker for macroangiopathy in Chinese Type 2 diabetic patients. ..
  3. Kempisty B, Sikora J, Lianeri M, Szczepankiewicz A, Czerski P, Hauser J, et al. MTHFD 1958G>A and MTR 2756A>G polymorphisms are associated with bipolar disorder and schizophrenia. Psychiatr Genet. 2007;17:177-81 pubmed
    ..Therefore, we examined the prevalence of 1958G>A polymorphism of MTHFD1 gene, encoding trifunctional folate enzyme 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-..
  4. Oterino A, Toriello M, Valle N, Castillo J, Alonso Arranz A, Bravo Y, et al. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache. 2010;50:99-168 pubmed publisher
    ..Determination of MTHFR C677T polymorphisms and Hcy levels may be useful to identify patients with a high risk of suffering from MA. ..
  5. Weiner A, Beresina O, Voronina E, Voropaeva E, Boyarskih U, Pospelova T, et al. Polymorphisms in folate-metabolizing genes and risk of non-Hodgkin's lymphoma. Leuk Res. 2011;35:508-15 pubmed publisher
    ..A significant association with NHL was observed only for MTHFD1 G1958A (allele G OR=1.382, P=0.05; genotype GA OR=2.316, P=0.01; genotype GG OR=2.153, P=0.03)...
  6. Mostowska A, Myka M, Lianeri M, Roszak A, Jagodzinski P. Folate and choline metabolism gene variants and development of uterine cervical carcinoma. Clin Biochem. 2011;44:596-600 pubmed publisher
    ..we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical ..
  7. Parle McDermott A, Mills J, Kirke P, Cox C, Signore C, Kirke S, et al. MTHFD1 R653Q polymorphism is a maternal genetic risk factor for severe abruptio placentae. Am J Med Genet A. 2005;132A:365-8 pubmed
    This study examined the relationship between folate/homocysteine-related genetic polymorphisms: MTHFD1 1958G --> A (R653Q), MTHFR 677C --> T (A222V), MTHFR 1298A --> C (E429A), and risk of severe abruptio placentae...
  8. Collin S, Metcalfe C, Zuccolo L, Lewis S, Chen L, Cox A, et al. Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2009;18:2528-39 pubmed publisher
    ..8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; ..
  9. Mostowska A, Hozyasz K, Jagodzinski P. Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population. Clin Genet. 2006;69:512-7 pubmed
    ..dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1) and reduced folate carrier 1 (RFC1)...

More Information


  1. Parle McDermott A, Kirke P, Mills J, Molloy A, Cox C, O Leary V, et al. Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet. 2006;14:768-72 pubmed
    ..We previously identified the 1958G>A (R653Q) polymorphism of the trifunctional enzyme MTHFD1 (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate ..
  2. Fredriksen A, Meyer K, Ueland P, Vollset S, Grotmol T, Schneede J. Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism. Hum Mutat. 2007;28:856-65 pubmed
    ..Asp919Gly); methionine synthase reductase (MTRR) c.66A>G (p.Ile22Met); methylenetetrahydrofolate dehydrogenase (MTHFD1) c.1958G>A (p.Arg653Gln); betaine homocysteine methyltransferase (BHMT) c.716G>A (known as 742G>A; p...
  3. Kelemen L, Goodman M, McGuire V, Rossing M, Webb P, Köbel M, et al. Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev. 2010;19:1822-30 pubmed publisher
    ..We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample ..
  4. Cheng J, Zhu W, Dao J, Li S, Li Y. Relationship between polymorphism of methylenetetrahydrofolate dehydrogenase and congenital heart defect. Biomed Environ Sci. 2005;18:58-64 pubmed
    To investigate the relationship between G1958A gene polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital heart disease (CHD) in North China...
  5. Chan J, Ugrasena D, Lum D, Lu Y, Yeoh A. Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children. Hematol Oncol. 2011;29:116-23 pubmed publisher
    ..GSTT1-present/null, GSTP1 1578A > G, NQO1 609C > T, MTHFR 677C > T, MTHFR 1298A > C, MTHFD1 1958G > A, 3'-TYMS 1494 6bp-deletion/insertion, 5'-TYMS 28bp-tandem repeats, and SLC19A1 80G > A) in a ..
  6. Stevens V, McCullough M, Pavluck A, Talbot J, Feigelson H, Thun M, et al. Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence. Cancer Epidemiol Biomarkers Prev. 2007;16:1140-7 pubmed
    ..methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthase [MTHFD1; odds ratio (OR), 1.40; 95% confidence interval (95% CI), 1.06-1...
  7. Carroll N, Pangilinan F, Molloy A, Troendle J, Mills J, Kirke P, et al. Analysis of the MTHFD1 promoter and risk of neural tube defects. Hum Genet. 2009;125:247-56 pubmed publisher
    Genetic variants in MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase/5,10-methenyltetrahydrofolate cyclohydrolase/ 10-formyltetrahydrofolate synthetase), an important folate metabolic enzyme, are associated with a number of common ..
  8. Stevens V, Rodriguez C, Sun J, Talbot J, Thun M, Calle E. No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:3612-4 pubmed publisher
    ..Thus, our findings do not support the hypothesis that common genetic variation in one-carbon metabolism genes influences prostate cancer risk. ..
  9. Neagos D, Cretu R, Tutulan Cunita A, Stoian V, Bohiltea L. Methylenetetrahydrofolate dehydrogenase (MTHFD) enzyme polymorphism as a maternal risk factor for trisomy 21: a clinical study. J Med Life. 2010;3:454-7 pubmed
    ..Our results show that the frequencies of MTHFD1 alleles, as well as the frequencies of MTHFD11958 genotypes (GG, GA, AA, GA+AA) do not correlate with DS ..
  10. Silva L, Silva J, Galbiatti A, Succi M, Ruiz M, Raposo L, et al. Head and neck carconogenesis: impact of MTHFD1 G1958A polymorphism. Rev Assoc Med Bras (1992). 2011;57:194-9 pubmed
    To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics...
  11. Liao Y, Zhang D, Zhou W, Meng F, Bao M, Xiang P, et al. Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China. Genet Mol Res. 2014;13:1764-73 pubmed publisher
    We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome...
  12. De Marco P, Merello E, Calevo M, Mascelli S, Raso A, Cama A, et al. Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958G>A polymorphism for neural tube defect risk. J Hum Genet. 2006;51:98-103 pubmed
    ..Given its key role in folate metabolism, the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene could represent an attractive candidate in NTD aetiology...
  13. van der Linden I, Heil S, Kouwenberg I, Den Heijer M, Blom H. The methylenetetrahydrofolate dehydrogenase (MTHFD1) 1958G>A variant is not associated with spina bifida risk in the Dutch population. Clin Genet. 2007;72:599-600 pubmed
  14. Palmieri A, Masiero E, Martinelli M, Scapoli L, Pezzetti F, Caramelli E, et al. The MTHFD1 gene is not involved in cleft lip with or without palate onset among the Italian population. Ann Hum Genet. 2008;72:297-9 pubmed publisher
    ..aim of this study was to evaluate the role of two polymorphisms of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene, the A1958G and the G401A variants, on the risk of CL/P in the Italian population...
  15. Curtin K, Slattery M, Ulrich C, Bigler J, Levin T, Wolff R, et al. Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet. Carcinogenesis. 2007;28:1672-9 pubmed
    ..II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated...
  16. Kruszyna Ł, Lianeri M, Rydzanicz M, Gajecka M, Szyfter K, Jagodziński P. Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer. Mol Biol Rep. 2010;37:241-7 pubmed publisher
    ..dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR) in patients with larynx cancer (n = 131) and controls (n = 250)...
  17. Bufalino A, Ribeiro Paranaíba L, Nascimento de Aquino S, Martelli Junior H, Oliveira Swerts M, Coletta R. Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population. Birth Defects Res A Clin Mol Teratol. 2010;88:980-6 pubmed publisher
    ..The aim of this study was to determine the involvement of polymorphic variants in four genes (MTHFR, MTHFD1, MTR, and SLC19A1) that encode proteins related to folic acid metabolism in the women with susceptibility for ..
  18. Chen J, Kyte C, Valcin M, Chan W, Wetmur J, Selhub J, et al. Polymorphisms in the one-carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study. Int J Cancer. 2004;110:617-20 pubmed
    ..Cytosolic serine hydroxymethyltransferase (cSHMT), methylenetetrahydrofolate dehydrogenase (MTHFD1) and glutamate carboxypeptidase II (GCPII) are key genes involved in this pathway...
  19. Brody L, Conley M, Cox C, Kirke P, McKeever M, Mills J, et al. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defect. Am J Hum Genet. 2002;71:1207-15 pubmed
    ..methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) for an association with NTDs in the Irish population...
  20. Boyles A, Billups A, Deak K, Siegel D, Mehltretter L, Slifer S, et al. Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006;114:1547-52 pubmed
  21. Mostowska A, Hozyasz K, Wojcicki P, Dziegelewska M, Jagodzinski P. Associations of folate and choline metabolism gene polymorphisms with orofacial clefts. J Med Genet. 2010;47:809-15 pubmed publisher
    ..176). The genetic variations in CBS, MTHFD1, MTHFR, MTR, MTRR, TCN2, BHMT2, CHDH, CHKA, and PEMT were not separately correlated with NCL/P risk...
  22. Shaw G, Lu W, Zhu H, Yang W, Briggs F, Carmichael S, et al. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med Genet. 2009;10:49 pubmed publisher
    ..8 (1.1-3.1), CBS (rs2851391) OR = 2.0 (1.2-3.1); CBS (rs234713) OR = 2.9 (1.3-6.7); MTHFD1 (rs2236224) OR = 1.7 (1.1-2.7); MTHFD1 (hcv11462908) OR = 0.2 (0-0.9); MTHFD2 (rs702465) OR = 0.6 (0.4-0...
  23. Shi M, Caprau D, Romitti P, Christensen K, Murray J. Genotype frequencies and linkage disequilibrium in the CEPH human diversity panel for variants in folate pathway genes MTHFR, MTHFD, MTRR, RFC1, and GCP2. Birth Defects Res A Clin Mol Teratol. 2003;67:545-9 pubmed
    ..Six polymorphisms in five folate metabolism-related genes (MTHFR, MTHFD, MTRR, GCP2, and RFC1) were genotyped on a collection of 1064 DNA samples from populations around the world, which ..
  24. Hol F, van der Put N, Geurds M, Heil S, Trijbels F, Hamel B, et al. Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects. Clin Genet. 1998;53:119-25 pubmed
    ..Our results so far provide no evidence for a major role of the methylenetetrahydrofolate-dehydrogenase (MTHFD) gene in NTD etiology...
  25. Christensen K, Rohlicek C, Andelfinger G, Michaud J, Bigras J, Richter A, et al. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. Hum Mutat. 2009;30:212-20 pubmed publisher
    Methylenetetrahydrofolate dehydrogenase)methenyltetrahydrofolate cyclohydrolase)formyltetrahydrofolate synthetase (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate (THF) derivatives for nucleotide synthesis...
  26. Hum D, Bell A, Rozen R, MacKenzie R. Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. J Biol Chem. 1988;263:15946-50 pubmed
    ..A region was identified which probably serves as a link between these two major domains of the human enzyme. The synthetase domain contains two regions that are homologous to consensus sequences for an ATP-binding site. ..
  27. Yang Y, Yuan Y, Hu W, Shang Q, Chen L. The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell carcinoma. Scand J Gastroenterol. 2017;:1-8 pubmed publisher
    ..However, little information is available concerning the role of MTHFD1L in cancer cells, and no studies have addressed such issues in esophageal cancer...
  28. Lévesque N, Christensen K, Van Der Kraak L, Best A, Deng L, Caldwell D, et al. Murine MTHFD1-synthetase deficiency, a model for the human MTHFD1 R653Q polymorphism, decreases growth of colorectal tumors. Mol Carcinog. 2017;56:1030-1040 pubmed publisher
    ..R653Q variant (∼20% homozygosity in Caucasians) in the synthetase domain of the folate-metabolizing enzyme MTHFD1 reduces purine synthesis...
  29. Dervieux T, Wessels J, van der Straaten T, Penrod N, Moore J, Guchelaar H, et al. Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics. 2009;19:935-44 pubmed publisher
    ..False-positive report probabilities were below 0.2, thereby indicating that true signals were likely detected in this cohort. These data indicate that gene-gene interactions impact MTX efficacy and tolerability in rheumatoid arthritis. ..
  30. MacFarlane A, Perry C, McEntee M, Lin D, Stover P. Mthfd1 is a modifier of chemically induced intestinal carcinogenesis. Carcinogenesis. 2011;32:427-33 pubmed publisher
    ..The Mthfd1 gene product, C1-tetrahydrofolate synthase, is a trifunctional enzyme that generates one-carbon substituted ..
  31. Allaire M, Li Y, MacKenzie R, Cygler M. The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution. Structure. 1998;6:173-82 pubmed
    ..The identity of the cyclohydrolase active site is not obvious. We propose that a conserved motif-Tyr52-X-X-X-Lys56- and/or a Ser49-Gln100-Pro102 triplet have a role in this activity. ..
  32. Kolin D, Dinulescu D, Crum C. Origin of clear cell carcinoma: nature or nurture?. J Pathol. 2017;: pubmed publisher
    ..These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment?..
  33. Moruzzi S, Guarini P, Udali S, Ruzzenente A, Guglielmi A, Conci S, et al. One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation. PLoS ONE. 2017;12:e0185792 pubmed publisher
    ..Genotyping for BHMT 716A>G, DHFR 19bp ins/del, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, TCII 776C>G and TS ..
  34. Saha T, Dutta S, Rajamma U, Sinha S, Mukhopadhyay K. A pilot study on the contribution of folate gene variants in the cognitive function of ADHD probands. Neurochem Res. 2014;39:2058-67 pubmed publisher
    ..MDR analysis exhibited independent effects and contribution of these sites to IQ, thus indicating a role of these genes in ADHD related cognitive deficit. ..
  35. Yang Y, Lin D, Chang S, Lin S, Lin S, Chiou R, et al. Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2010;54:206-11 pubmed publisher
    ..The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively. Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients. ..
  36. Jin G, Huang J, Hu Z, Dai J, Tang R, Chen Y, et al. Genetic variants in one-carbon metabolism-related genes contribute to NSCLC prognosis in a Chinese population. Cancer. 2010;116:5700-9 pubmed publisher
    ..71-0.99) and DHFR rs1650697 G>A (allelic HR, 0.83; 95% CI, 0.70-0.99) and with unfavorable prognosis for MTHFD1 rs1950902 G>A with borderline significance (allelic HR, 1.18; 95% CI, 0.99-1.40)...
  37. Liu G, Qi C, Xu Q, Wu B, Wang Y, Xue C. Lack of association between methylenetetrahydrofolate dehydrogenase 1 G1958A polymorphism and prostate cancer risk: a meta-analysis. Tumour Biol. 2014;35:2029-33 pubmed publisher
    The methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism G1958A has been extensively investigated as a potential risk factor for prostate cancer (PCa), but the results have thus far been inconclusive...
  38. Dorszewska J, Florczak J, Rozycka A, Kempisty B, Jaroszewska Kolecka J, Chojnacka K, et al. Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases. Acta Neurobiol Exp (Wars). 2007;67:113-29 pubmed
    ..Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins...
  39. Pjetri E, Zeisel S. Deletion of one allele of Mthfd1 (methylenetetrahydrofolate dehydrogenase 1) impairs learning in mice. Behav Brain Res. 2017;332:71-74 pubmed publisher
    The MTHFD1 gene encodes for methylenetetrahydrofolate dehydrogenase 1, an enzyme that has an important role in folate-mediated one-carbon metabolism...
  40. Ivanov A, Nash Barboza S, Hinkis S, Caudill M. Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted. J Am Diet Assoc. 2009;109:313-8 pubmed publisher
    ..gene (ie, 5465G-->A; rs7946 and -744G-->C; rs12325817) and in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene (ie, 1958G-->A; rs2236225)...
  41. Fan B, Chen T, Grosskreutz C, Pasquale L, Rhee D, DelBono E, et al. Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma. Mol Vis. 2008;14:2484-91 pubmed
    ..MTHFR], methionine synthase [MTR], methionine synthase reductase [MTRR], methylenetetrahydrofolate dehydrogenase [MTHFD1], and cystathionine beta-synthase [CBS]) were genotyped...
  42. Zampieri B, Biselli J, Goloni Bertollo E, Pavarino E. BHMT G742A and MTHFD1 G1958A polymorphisms and Down syndrome risk in the Brazilian population. Genet Test Mol Biomarkers. 2012;16:628-31 pubmed publisher
    ..The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated...
  43. MacKenzie R, Mejia N, Yang X. Methylenetetrahydrofolate dehydrogenases in normal and transformed mammalian cells. Adv Enzyme Regul. 1988;27:31-9 pubmed
  44. Zdoukopoulos N, Zintzaras E. Genetic risk factors for placental abruption: a HuGE review and meta-analysis. Epidemiology. 2008;19:309-23 pubmed publisher
    ..Seven polymorphisms (F5 Arg506Gln, F5 Met385Thr, F2 G20210A, MTHFR A1298C, MTHFD1 Arg653Gln, NOS3 Glu298Asp, AGT Met235Thr) show significant association in individual studies...
  45. Crişan T, Trifa A, Farcaş M, Militaru M, Netea M, Pop I, et al. The MTHFD1 c.1958 G>A polymorphism and recurrent spontaneous abortions. J Matern Fetal Neonatal Med. 2011;24:189-92 pubmed publisher
    ..1958 G>A SNP in the MTHFD1 gene encoding a trifunctional enzyme involved in DNA synthesis and folate metabolism...
  46. Parveen F, Tuteja M, Agrawal S. Polymorphisms in MTHFR, MTHFD, and PAI-1 and recurrent miscarriage among North Indian women. Arch Gynecol Obstet. 2013;288:1171-7 pubmed publisher
    The aim of this study was to investigate the association between MTHFR C677T, A1298C, MTHFD G1958A and plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism among first trimester recurrent miscarriages...
  47. Christensen K, Dahhou M, Kramer M, Rozen R. The MTHFD1 1958G>A variant is associated with elevated C-reactive protein and body mass index in Canadian women from a premature birth cohort. Mol Genet Metab. 2014;111:390-392 pubmed publisher
    b>MTHFD1 1958G>A, a polymorphism in folate metabolism, increases risk of pregnancy complications. A mouse model exhibited developmental defects, increased weight and decreased leukocyte counts...
  48. Sutherland H, Hermile H, Sanche R, Menon S, Lea R, Haupt L, et al. Association study of MTHFD1 coding polymorphisms R134K and R653Q with migraine susceptibility. Headache. 2014;54:1506-14 pubmed publisher
    ..nucleotide polymorphisms (SNPs), rs1950902 (C401T; R134K) and rs2236225 (G1958A; R653Q), in MTHF dehydrogenase (MTHFD1) are associated with migraine in an Australian case-control population...
  49. Dorszewska J, Prendecki M, Oczkowska A, Dezor M, Kozubski W. Molecular Basis of Familial and Sporadic Alzheimer's Disease. Curr Alzheimer Res. 2016;13:952-63 pubmed
    ..related to the immunological cause (TREM2) of the disease are a disorder of the lipid (ABCA1, ABCA7) or biothiol (MTHFD1) metabolism and of the transport of metabolites (BIN1)...
  50. Meyer K, Fredriksen A, Ueland P. MALDI-TOF MS genotyping of polymorphisms related to 1-carbon metabolism using common and mass-modified terminators. Clin Chem. 2009;55:139-49 pubmed publisher
    ..CBS 844ins68 and 699C>T, CTH 1364G>T, DHFR del19, NOS3 -786T>C and 894G>T, FOLR1 1314G>A, MTHFD1 -105T>C and 1958G>A, MTHFR 677C>T and 1298A>C, MTR 2756A>G, MTRR 66A>G and 524C>T, SLC19A1 ..
  51. Field M, Kamynina E, Watkins D, Rosenblatt D, Stover P. Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis. Proc Natl Acad Sci U S A. 2015;112:400-5 pubmed publisher
    An inborn error of metabolism associated with mutations in the human methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene has been identified...
  52. Yeoh A, Lu Y, Chan J, Chan Y, Ariffin H, Kham S, et al. Genetic susceptibility to childhood acute lymphoblastic leukemia shows protection in Malay boys: results from the Malaysia-Singapore ALL Study Group. Leuk Res. 2010;34:276-83 pubmed publisher
    ..Our study has suggested the importance of gender and race in modulating ALL susceptibility via the folate metabolic pathway. ..
  53. Schmidt A, Wu H, MacKenzie R, Chen V, Bewly J, Ray J, et al. Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase. Biochemistry. 2000;39:6325-35 pubmed
    ..On the basis of structural and mutagenesis data, we propose a reaction mechanism for both activities, the dehydrogenase and the cyclohydrolase. ..
  54. Li Y, Cheng J, Zhu W, Dao J, Yan L, Li M, et al. [Study of serum Hcy and polymorphisms of Hcy metabolic enzymes in 192 families affected by congenital heart disease]. Beijing Da Xue Xue Bao Yi Xue Ban. 2005;37:75-80 pubmed
    To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and to assess the association of single or combined gene mutations with folic acid, Vit...
  55. Zhang H, Ma H, Li L, Zhang Z, Xu Y. Association of methylenetetrahydrofolate dehydrogenase 1 polymorphisms with cancer: a meta-analysis. PLoS ONE. 2013;8:e69366 pubmed publisher
    ..the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results...
  56. Li S, Rong M, Iacopetta B. Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in human breast cancer. Oncol Rep. 2006;15:221-5 pubmed
    ..Our results show that polymorphisms in two genes involved in methyl group metabolism are associated with hormone receptor content and DNA methylation frequency in breast cancer, however these observations are unlikely to be linked. ..
  57. Meng J, Han L, Zhuang B. Association between MTHFD1 polymorphisms and neural tube defect susceptibility. J Neurol Sci. 2015;348:188-94 pubmed publisher
    ..The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene has been proved to play an important role in folate metabolism, which was strongly associated with the high ..
  58. Peri K, Belanger C, MacKenzie R. Nucleotide sequence of the human NAD-dependent methylene tetrahydrofolate dehydrogenase-cyclohydrolase. Nucleic Acids Res. 1989;17:8853 pubmed
  59. Wu J, Bao Y, Lu X, Wu L, Zhang T, Guo J, et al. Polymorphisms in MTHFD1 Gene and Susceptibility to Neural Tube Defects: A Case-Control Study in a Chinese Han Population with Relatively Low Folate Levels. Med Sci Monit. 2015;21:2630-7 pubmed publisher
    The polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD1) has been reported as a risk factor for neural tube defects (NTDs)...
  60. Prasoona K, Sunitha T, Srinadh B, Deepika M, Kumari T, Jyothy A. Paternal transmission of MTHFD1 G1958A variant predisposes to neural tube defects in the offspring. Dev Med Child Neurol. 2016;58:625-31 pubmed publisher
    This study aimed to evaluate the role of methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A variant (rs2236225) as a 'maternal, paternal, or embryonic' genetic risk factor for neural tube defect (NTD) susceptibility...
  61. Field M, Kamynina E, Stover P. MTHFD1 regulates nuclear de novo thymidylate biosynthesis and genome stability. Biochimie. 2016;126:27-30 pubmed publisher
    ..In this overview, we summarize recent evidence that the enzyme MTHFD1 plays an essential role in FOCM in humans and in mice, and that it determines the partitioning of folate-activated ..
  62. Lee D, Wong C. The folate cycle is a new metabolic weakness of cancer. Mol Cell Oncol. 2017;4:e1327004 pubmed publisher
    ..Folate cycle stagnation via inhibition of its mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) greatly induced oxidative stress improving HCC cells' response to sorafenib...
  63. Ding Y, Pedersen E, Svingen G, Helgeland Ø, Gregory J, Løland K, et al. Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms Modify the Associations of Plasma Glycine and Serine With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris in WENBIT (Western Norway B Vitamin Intervention Trial). Circ Cardiovasc Genet. 2016;9:541-547 pubmed publisher
    Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism...
  64. Zheng J, Lu X, Liu H, Zhao P, Li K, Li L. MTHFD1 polymorphism as maternal risk for neural tube defects: a meta-analysis. Neurol Sci. 2015;36:607-16 pubmed publisher
    Recently, the association between methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A polymorphism and neural tube defects (NTD) susceptibility has been widely investigated; however, the results remained inconclusive...
  65. Collin S, Metcalfe C, Refsum H, Lewis S, Smith G, Cox A, et al. Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:2833-8 pubmed publisher
    ..Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication. ..
  66. Stamp L, Chapman P, O Donnell J, Zhang M, James J, Frampton C, et al. Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenet Genomics. 2010;20:367-76 pubmed publisher
    ..002), MTRR 66A>G (P<0.0001), MTHFD1 1958G>A (P=0.001) and SHMT 1420C>T (P=0...
  67. Stumpf A, van der Meijden E, van Bergen C, Willemze R, Falkenburg J, Griffioen M. Identification of 4 new HLA-DR-restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity. Blood. 2009;114:3684-92 pubmed publisher
    ..The selective recognition of hematopoietic cells as well as the balanced population frequencies and common HLA-DR restriction elements make the novel mHags possible targets for development of immunotherapeutic strategies. ..
  68. Matakidou A, el Galta R, Rudd M, Webb E, Bridle H, Eisen T, et al. Prognostic significance of folate metabolism polymorphisms for lung cancer. Br J Cancer. 2007;97:247-52 pubmed
    ..methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small ..
  69. Mejia N, MacKenzie R. NAD-dependent methylenetetrahydrofolate dehydrogenase is expressed by immortal cells. J Biol Chem. 1985;260:14616-20 pubmed
    ..Its physiological role is unknown, but it is proposed that it promotes purine synthesis and perhaps contributes to the methionine dependence and rapid growth observed for many established lines. ..
  70. Balduino Victorino D, de Godoy M, Goloni Bertollo E, Pavarino Ã. Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis. Dis Markers. 2014;2014:517504 pubmed publisher
    ..Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies ..
  71. Eussen S, Vollset S, Hustad S, Midttun Ø, Meyer K, Fredriksen A, et al. Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2010;19:28-38 pubmed publisher
    ..In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk. ..
  72. Rasti M, Tavasoli P, Monabati A, Entezam M. Association between HIC1 and RASSF1A promoter hypermethylation with MTHFD1 G1958A polymorphism and clinicopathological features of breast cancer in Iranian patients. Iran Biomed J. 2009;13:199-206 pubmed
    ..of HIC1 and RASSF1A gene promoters and their association with methylene tetrahydrofolate dehydrogenase (MTHFD1) G1958A polymorphism and major clinical and pathological features of breast cancer in Iranian women...
  73. Hazra A, Fuchs C, Kawasaki T, Kirkner G, Hunter D, Ogino S. Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer. Cancer Causes Control. 2010;21:331-45 pubmed publisher
    ..Collectively, these exploratory data provide suggestive evidence for the association of MTHFR 429 Ala/ Ala and TCN2 259 Arg/Arg and CIMP status in colorectal cancer. ..
  74. Furness D, Fenech M, Khong Y, Romero R, Dekker G. One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency. Am J Obstet Gynecol. 2008;199:276.e1-8 pubmed publisher
    ..synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A...
  75. Khatami M, Ratki F, Tajfar S, Akrami F. Relationship of the MTHFD1 (rs2236225), eNOS (rs1799983), CBS (rs2850144) and ACE (rs4343) gene polymorphisms in a population of Iranian pediatric patients with congenital heart defects. Kaohsiung J Med Sci. 2017;33:442-448 pubmed publisher
    ..To investigate the association of 4 single nucleotide polymorphisms (SNPs) in the MTHFD1, eNOS, CBS and ACE genes, we evaluated their relationship with CHD in Iranian patients...
  76. Fu C, Sikandar A, Donner J, Zaburannyi N, Herrmann J, Reck M, et al. The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD. Nat Commun. 2017;8:1529 pubmed publisher
    ..We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the ..
  77. Oterino A, Valle N, Pascual J, Bravo Y, Muñoz P, Castillo J, et al. Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele. Brain Res Mol Brain Res. 2005;139:163-8 pubmed
    ..Individually, thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS) polymorphisms did not modify the general risk for suffering migraine...
  78. de Jonge R, Hooijberg J, van Zelst B, Jansen G, Jansen G, van Zantwijk C, et al. Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. Blood. 2005;106:717-20 pubmed
    ..synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced ..