reduced folate carrier


Gene Symbol: reduced folate carrier
Description: solute carrier family 19 member 1
Alias: CHMD, FOLT, IFC1, REFC, RFC1, folate transporter 1, IFC-1, RFC, intestinal folate carrier 1, placental folate transporter, reduced folate carrier 1, reduced folate carrier protein, solute carrier family 19 (folate transporter), member 1
Species: human
Products:     reduced folate carrier

Top Publications

  1. Hou Z, Stapels S, Haska C, Matherly L. Localization of a substrate binding domain of the human reduced folate carrier to transmembrane domain 11 by radioaffinity labeling and cysteine-substituted accessibility methods. J Biol Chem. 2005;280:36206-13 pubmed
    The human reduced folate carrier (hRFC) mediates the membrane transport of reduced folates and classical anti-folates into mammalian cells...
  2. Dervieux T, Furst D, Lein D, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50:2766-74 pubmed
    Methotrexate (MTX) enters cells through the reduced folate carrier (RFC-1) and exerts part of its effects through polyglutamation to MTX polyglutamates (MTXPGs) and inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide ..
  3. 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
    ..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; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 ..
  4. Witt T, Stapels S, Matherly L. Restoration of transport activity by co-expression of human reduced folate carrier half-molecules in transport-impaired K562 cells: localization of a substrate binding domain to transmembrane domains 7-12. J Biol Chem. 2004;279:46755-63 pubmed
    ..and classical antifolates such as methotrexate are actively transported into mammalian cells by the reduced folate carrier (RFC)...
  5. Flatley R, Payton S, Taub J, Matherly L. Primary acute lymphoblastic leukemia cells use a novel promoter and 5'noncoding exon for the human reduced folate carrier that encodes a modified carrier translated from an upstream translational start. Clin Cancer Res. 2004;10:5111-22 pubmed
    The human reduced folate carrier (hRFC) is reported to be regulated by up to seven alternatively spliced noncoding exons (A1, A2, A, B, C, D, and E)...
  6. Chatzikyriakidou A, Georgiou I, Voulgari P, Papadopoulos C, Tzavaras T, Drosos A. Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene could affect rheumatoid arthritis patient response to methotrexate therapy. Rheumatol Int. 2007;27:1057-61 pubmed
    The reduced folate carrier (RFC) protein (SLC19A1-gene) has central role in the uptake and intracellular accumulation of folates...
  7. Shen M, Rothman N, Berndt S, He X, Yeager M, Welch R, et al. Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer. 2005;49:299-309 pubmed
    ..002 and P=0.07, respectively). In summary, three genetic variants in folate metabolism genes are associated with an increased risk of lung cancer in Xuan Wei, China. ..
  8. Levine A, Lee W, Figueiredo J, Conti D, Vandenberg D, Davis B, et al. Variation in folate pathway genes and distal colorectal adenoma risk: a sigmoidoscopy-based case-control study. Cancer Causes Control. 2011;22:541-52 pubmed publisher
    ..Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after ..
  9. Payton S, Haska C, Flatley R, Ge Y, Matherly L. Effects of 5' untranslated region diversity on the posttranscriptional regulation of the human reduced folate carrier. Biochim Biophys Acta. 2007;1769:131-8 pubmed
    The human RFC (hRFC) gene is regulated by five major 5' non-coding exons, characterized by alternate transcription start sites and splice forms...

More Information


  1. Deng Y, Hou Z, Wang L, Cherian C, Wu J, Gangjee A, et al. Role of lysine 411 in substrate carboxyl group binding to the human reduced folate carrier, as determined by site-directed mutagenesis and affinity inhibition. Mol Pharmacol. 2008;73:1274-81 pubmed publisher
    b>Reduced folate carrier (RFC) is the major membrane transporter for folates and antifolates in mammalian tissues...
  2. Moscow J, Gong M, He R, Sgagias M, Dixon K, Anzick S, et al. Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells. Cancer Res. 1995;55:3790-4 pubmed
    Our laboratory has previously reported the isolation of a murine cDNA which restores reduced folate carrier (RFC) activity and methotrexate (MTX) sensitivity to a MTX-resistant, transport-deficient human breast cancer cell line (MTXR ZR-..
  3. Białecka M, Kurzawski M, Roszmann A, Robowski P, Sitek E, Honczarenko K, et al. Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. Pharmacogenet Genomics. 2012;22:716-24 pubmed publisher
    ..folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1)...
  4. Eklöf V, Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Palmqvist R. The reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T polymorphisms and the risk of colorectal cancer: a nested case-referent study. Scand J Clin Lab Invest. 2008;68:393-401 pubmed publisher
    ..In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal cancer, taking ..
  5. Hou Z, Matherly L. Oligomeric structure of the human reduced folate carrier: identification of homo-oligomers and dominant-negative effects on carrier expression and function. J Biol Chem. 2009;284:3285-93 pubmed publisher
    The ubiquitously expressed reduced folate carrier (RFC) is the major transport system for folate cofactors in mammalian cells and tissues...
  6. Hou Z, Ye J, Haska C, Matherly L. Transmembrane domains 4, 5, 7, 8, and 10 of the human reduced folate carrier are important structural or functional components of the transmembrane channel for folate substrates. J Biol Chem. 2006;281:33588-96 pubmed
    The human reduced folate carrier (hRFC) facilitates membrane transport of folates and antifolates. hRFC is characterized by 12 transmembrane domains (TMDs)...
  7. Wang L, Chen W, Wang J, Tan Y, Zhou Y, Ding W, et al. Reduced folate carrier gene G80A polymorphism is associated with an increased risk of gastroesophageal cancers in a Chinese population. Eur J Cancer. 2006;42:3206-11 pubmed
    Low folate intake has been associated with an increased risk of both oesophageal and gastric cancers. Reduced folate carrier (RFC1, also named SLC19A1) is an essential folate transporter and functions as a bidirectional anion exchanger, ..
  8. Ifergan I, Jansen G, Assaraf Y. The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis. J Biol Chem. 2008;283:20687-95 pubmed publisher
    The reduced folate carrier (RFC), a bidirectional anion transporter, is the major uptake route of reduced folates essential for a spectrum of biochemical reactions and thus cellular proliferation...
  9. Cao W, Matherly L. Characterization of a cysteine-less human reduced folate carrier: localization of a substrate-binding domain by cysteine-scanning mutagenesis and cysteine accessibility methods. Biochem J. 2003;374:27-36 pubmed
    The human reduced folate carrier (hRFC) mediates the transport of reduced folates and classical anti-folates into mammalian cells...
  10. Rothem L, Aronheim A, Assaraf Y. Alterations in the expression of transcription factors and the reduced folate carrier as a novel mechanism of antifolate resistance in human leukemia cells. J Biol Chem. 2003;278:8935-41 pubmed
    The human reduced folate carrier (hRFC) is the dominant transporter mediating the uptake of reduced folate cofactors and antifolate anticancer drugs...
  11. Rah H, Choi Y, Jeon Y, Choi Y, Cha S, Choi D, et al. Solute Carrier Family 19, member 1 (SLC19A1) polymorphisms (-43T>C, 80G>A, and 696C>T), and haplotypes in idiopathic recurrent spontaneous abortion in a Korean population. Reprod Sci. 2012;19:513-9 pubmed publisher
    ..05 for each). The associations between idiopathic RSA occurrence and SLC19A1 -43T>C/80G>A/696C>T polymorphisms were identified and can be developed as biomarkers for RSA risk. ..
  12. Hou Z, Cherian C, Drews J, Wu J, Matherly L. Identification of the minimal functional unit of the homo-oligomeric human reduced folate carrier. J Biol Chem. 2010;285:4732-40 pubmed publisher
    The reduced folate carrier (RFC) is the major transport system for folates in mammals...
  13. Yates Z, Lucock M. G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism. Life Sci. 2005;77:2735-42 pubmed
    Dietary folate is absorbed in the jejunum by the 'Reduced Folate Carrier' binding protein. This protein also sequesters extracellular folate for use by many cells in the body...
  14. Matherly L, Hou Z, Deng Y. Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev. 2007;26:111-28 pubmed
    ..of the biology of the physiologically and pharmacologically important transport system termed the "reduced folate carrier" (RFC)...
  15. Stanisławska Sachadyn A, Mitchell L, Woodside J, Buckley P, Kealey C, Young I, et al. The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women. Ann Hum Genet. 2009;73:484-91 pubmed publisher
    ..As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on ..
  16. Wang D, Wang F, Shi K, Tao H, Li Y, Zhao R, et al. Lower Circulating Folate Induced by a Fidgetin Intronic Variant Is Associated With Reduced Congenital Heart Disease Susceptibility. Circulation. 2017;135:1733-1748 pubmed publisher
    ..Mechanistically, increased FIGN expression led to the accumulation of both reduced folate carrier 1 and dihydrofolate reductase via inhibition of their proteasomal degradation, which promoted folate ..
  17. Shiomi Y, Nishitani H. Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication. Genes (Basel). 2017;8: pubmed publisher
    ..PCNA is loaded onto chromatin by PCNA-loading replication factor C (RFC) complexes. Both RFC1-RFC and Ctf18-RFC fundamentally function as PCNA loaders...
  18. Macias Gonzalez M, Martín Núñez G, Garrido Sanchez L, Garcia Fuentes E, Tinahones F, Morcillo S. Decreased blood pressure is related to changes in NF-kB promoter methylation levels after bariatric surgery. Surg Obes Relat Dis. 2018;: pubmed publisher
    ..Regarding SLC19A1, this gene could position as a potential target linking inflammation and insulin resistance. ..
  19. Nunes C, Silva C, Correia Branco A, Martel F. Lack of effect of the procarcinogenic 17β-estradiol on nutrient uptake by the MCF-7 breast cancer cell line. Biomed Pharmacother. 2017;90:287-294 pubmed publisher
    ..Finally, 3H-folic acid uptake was also not affected by E2, both in the absence and presence of the RFC1 inhibitor, methotrexate...
  20. Mazumdar M, Valeri L, Rodrigues E, Ibne Hasan M, Hamid R, Paul L, et al. Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele. Birth Defects Res A Clin Mol Teratol. 2015;103:754-62 pubmed publisher
    ..25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways. ..
  21. Kawami M, Miyamoto M, Yumoto R, Takano M. Methotrexate influx via folate transporters into alveolar epithelial cell line A549. Drug Metab Pharmacokinet. 2015;30:276-81 pubmed publisher
    ..We then examined the role of two folate transporters in MTX influx, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT)...
  22. Lu D, Cai H, Park S, Siddiqui S, Premont R, Schmalzigaug R, et al. Nuclear GIT2 is an ATM substrate and promotes DNA repair. Mol Cell Biol. 2015;35:1081-96 pubmed publisher
    ..including stabilization of BRCA1 in repair complexes; upregulation of repair proteins, including HMGN1 and RFC1; and regulation of poly(ADP-ribose) polymerase activity...
  23. Torres A, Newton S, Crompton B, Borzutzky A, Neufeld E, Notarangelo L, et al. CSF 5-Methyltetrahydrofolate Serial Monitoring to Guide Treatment of Congenital Folate Malabsorption Due to Proton-Coupled Folate Transporter (PCFT) Deficiency. JIMD Rep. 2015;24:91-6 pubmed publisher well as bypass autoantibody-blocked folate receptors and enter the cerebrospinal fluid by way of the reduced folate carrier. This route elevates the 5-methyltetrahydrofolate level within the central nervous system and can prevent ..
  24. Dudeja P, Kode A, Alnounou M, Tyagi S, Torania S, Subramanian V, et al. Mechanism of folate transport across the human colonic basolateral membrane. Am J Physiol Gastrointest Liver Physiol. 2001;281:G54-60 pubmed
    ..human colonic basolateral membrane preparations and specific polyclonal antibodies against the human reduced folate carrier (hRFC) has shown expression of the hRFC protein at this membrane domain...
  25. Iparraguirre L, Gutierrez Camino A, Umerez M, Martin Guerrero I, Astigarraga I, Navajas A, et al. MiR-pharmacogenetics of methotrexate in childhood B-cell acute lymphoblastic leukemia. Pharmacogenet Genomics. 2016;26:517-525 pubmed
    ..In this study, we detected three SNPs in miR-5189, miR-595, and miR-6083 that might affect SLC46A1, SLC19A1, and SLCO1A2 MTX transport gene regulation and could affect MTX levels in patients with pediatric B-cell ALL. ..
  26. Moruzzi S, Udali S, Ruzzenente A, Guglielmi A, Guarini P, Martinelli N, et al. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers. PLoS ONE. 2016;11:e0167534 pubmed publisher
    ..polymorphisms: DHFR 19bp ins/del, TS 2rpt-3rpt, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, BHMT 716 A>G, TC II 776C>G...
  27. Walter R, Mairinger F, Werner R, Vollbrecht C, Hager T, Schmid K, et al. Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome. Oncotarget. 2016;7:20166-79 pubmed publisher
  28. Subramanian V, Reidling J, Said H. Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine. Am J Physiol Cell Physiol. 2008;295:C828-35 pubmed publisher
    ..This increase was associated with an increase in the level of expression of the human reduced folate carrier (hRFC) and the human proton-coupled folate transporter (hPCFT) both at the protein and mRNA levels with ..
  29. Morin I, Devlin A, Leclerc D, Sabbaghian N, Halsted C, Finnell R, et al. Evaluation of genetic variants in the reduced folate carrier and in glutamate carboxypeptidase II for spina bifida risk. Mol Genet Metab. 2003;79:197-200 pubmed
    ..H475Y) mutation in glutamate carboxypeptidase II (GCPII) and the 80A-->G (H27R) change in the reduced folate carrier RFC-1...
  30. Hegyi M, Arany A, Semsei A, Csordás K, Eipel O, Gézsi A, et al. Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma. Oncotarget. 2017;8:9388-9398 pubmed publisher
    ..In both univariate and multivariate analyses the SNPs ABCB1 rs928256, ABCC3 rs4793665, GGH rs3758149, and NR1I2 rs3814058 SNPs were relevant. These SNPs should be considered in future dose individualization during treatment. ..
  31. Ahmad Najar R, Rahat B, Hussain A, Thakur S, Kaur J, Kaur J, et al. Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation. Mol Nutr Food Res. 2016;60:1501-13 pubmed publisher
    ..folate levels with decreased uptake of folate, further associated with decreased expression levels of reduced folate carrier (RFC) and increased expression levels of folate exporter (ABCG2) at both mRNA and protein levels, which in ..
  32. Kishi S, Cheng C, French D, Pei D, Das S, Cook E, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007;109:4151-7 pubmed
    ..During the consolidation phase, when antifolates predominated, the reduced folate carrier polymorphism predicted gastrointestinal toxicity (OR, 10.4 [95% CI, 1.35-80...
  33. Moya P, Salazar J, Arranz M, Díaz Torné C, del Río E, Casademont J, et al. Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients. Pharmacogenomics. 2016;17:25-9 pubmed publisher
    ..We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. We studied 194 RA patients receiving MTX monotherapy...
  34. Lakkakula B, Murthy J, Gurramkonda V. Relationship between reduced folate carrier gene polymorphism and non-syndromic cleft lip and palate in Indian population. J Matern Fetal Neonatal Med. 2015;28:329-32 pubmed publisher
    ..The purpose of this study was to identify the prevalence of reduced folate carrier 1 (RFC1) A80G polymorphism and to further delineate its association with non-syndromic cleft lip and palate ..
  35. Pelkonen L, Sato K, Reinisalo M, Kidron H, Tachikawa M, Watanabe M, et al. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line. Mol Pharm. 2017;14:605-613 pubmed publisher
    ..MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 ..
  36. Naggar H, Fei Y, Ganapathy V, Smith S. Regulation of reduced-folate transporter-1 (RFT-1) by homocysteine and identity of transport systems for homocysteine uptake in retinal pigment epithelial (RPE) cells. Exp Eye Res. 2003;77:687-97 pubmed
    ..We conclude that several transport systems operate in ARPE-19 cells for the entry of Hcy and that high levels of Hcy have deleterious effects on the expression and activity of RFT-1 in these cells. ..
  37. Xu K, Zhang M, Zhao Q, Yu F, Guo H, Wang C, et al. Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis. Nature. 2013;497:268-71 pubmed publisher
    ..The folate-binding protein FolT is nearly parallel to the membrane and is bound almost entirely by EcfT, which adopts an L?shape and connects to ..
  38. Thakur S, More D, Rahat B, Khanduja K, Kaur J. Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency. Mol Cell Biochem. 2016;411:151-60 pubmed publisher
    ..e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level...
  39. Wang J, Li G. Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells. Genet Mol Res. 2014;13:5313-21 pubmed publisher
    ..In this study, the relationship between reduced folate carrier (RFC) gene expression and intracellular drug concentration in MTX-resistant osteosarcoma cells (Saos-2) ..
  40. Said H, Chatterjee N, Haq R, Subramanian V, Ortiz A, Matherly L, et al. Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency. Am J Physiol Cell Physiol. 2000;279:C1889-95 pubmed
    ..constant of the uptake process, 2) was associated with a marked increase in the steady-state mRNA level of reduced folate carrier-1 and in the level of the expressed protein at the intestinal BBM, and 3) was associated with a marked (&..
  41. Wettergren Y, Odin E, Nilsson S, Willen R, Carlsson G, Gustavsson B. Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients. Cancer Detect Prev. 2005;29:348-55 pubmed
    ..The purpose of this study was to analyze if the folate level and the gene expression levels of reduced folate carrier (RFC-1) and folylpolyglutamate synthase (FPGS) had impact on the expression of DCC splice variants...
  42. Mirgal D, Ghosh K, Mahanta J, Dutta P, Shetty S. Possible selection of host folate pathway gene polymorphisms in patients with malaria from a malaria endemic region in North East India. Trans R Soc Trop Med Hyg. 2016;110:294-8 pubmed publisher
    ..MTRR) A66G, glutamate carboxypeptidase II (GCPII) C1561T, cystathionine beta-synthase (CBS) 844ins68, reduced folate carrier-1 (RFC-1) G80A, serine hydroxymethyltransferase (SHMT) C1420T, methionine synthase (MTR) A2756G, MTHFR ..
  43. Fodinger M, Dierkes J, Skoupy S, Röhrer C, Hagen W, Puttinger H, et al. Effect of glutamate carboxypeptidase II and reduced folate carrier polymorphisms on folate and total homocysteine concentrations in dialysis patients. J Am Soc Nephrol. 2003;14:1314-9 pubmed
    This study was designed to examine the effect of two single nucleotide polymorphisms in the reduced folate carrier 1 (RFC1 80G>A) and the glutamate carboxypeptidase 2 (GCP2 1561C>T) gene on total homocysteine (tHcy) plasma level and ..
  44. Winkelmayer W, Eberle C, Sunder Plassmann G, Fodinger M. Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney Int. 2003;63:2280-5 pubmed
    The effect of the glutamate carboxypeptidase II GCP2 1561C>T and the reduced folate carrier 1 RFC1 80G>A polymorphisms on folate and total homocysteine (tHcy) plasma levels of kidney transplant patients are unknown...
  45. Steluti J, Carvalho A, Carioca A, Miranda A, Gattás G, Fisberg R, et al. Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era. Nutrients. 2017;9: pubmed publisher
    ..33 for MTHFR (rs1801133), 0.24 for MTHFR (rs1801131), 0.19 for MTR (rs1805087), 0.42 for MTRR (rs1801394), 0.46 for RFC1 (rs1051266), and 0.47 for DHFR (19-bp deletion)...
  46. Shah K, Raghavan S, Hou Z, Matherly L, Gangjee A. Development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores). J Mol Graph Model. 2018;81:125-133 pubmed publisher
    ..tumors over normal cells via the proton-coupled folate transporter (PCFT) over the ubiquitously expressed reduced folate carrier (RFC)...
  47. Cao L, Wang Y, Zhang R, Dong L, Cui H, Fang Y, et al. Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway. Childs Nerv Syst. 2018;34:277-284 pubmed publisher
    ..there was a statistical difference in the allele and genotype frequencies of rs1051266 in reduced folate carrier1 (RFC1) gene between cases and controls (P = 0.013, 0...
  48. Ashokkumar B, Nabokina S, Ma T, Said H. Identification of dynein light chain road block-1 as a novel interaction partner with the human reduced folate carrier. Am J Physiol Gastrointest Liver Physiol. 2009;297:G480-7 pubmed publisher
    The reduced folate carrier (RFC) is a major folate transport system in mammalian cells. RFC is highly expressed in the intestine and believed to play a role in folate absorption...
  49. Fintelman Rodrigues N, Correa J, Santos J, Pimentel M, Santos Rebouças C. Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome. Dis Markers. 2009;26:155-61 pubmed publisher
    ..We compared the frequency of CBS 844ins68, MTR 2756A>G, RFC-1 80G&gt A and TC 776C>G polymorphisms among 114 case mothers and 110 matched controls, in order to observe ..
  50. Laverdiere C, Chiasson S, Costea I, Moghrabi A, Krajinovic M. Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood. 2002;100:3832-4 pubmed
    ..Recently, a G(80)A polymorphism has been described in the reduced folate carrier gene (RFC1), which encodes the major MTX transporter...
  51. Biselli J, Brumati D, Frigeri V, Zampieri B, Goloni Bertollo E, Pavarino Bertelli E. A80G polymorphism of reduced folate carrier 1 (RFC1) and C776G polymorphism of transcobalamin 2 (TC2) genes in Down's syndrome etiology. Sao Paulo Med J. 2008;126:329-32 pubmed
    ..This study therefore had the objective of investigating the A80G polymorphism of the reduced folate carrier 1 (RFC1) gene and the C776G polymorphism of the transcobalamin 2 (TC2) gene as maternal risk factors for DS ..
  52. O Byrne M, Au K, Morrison A, Lin J, Fletcher J, Ostermaier K, et al. Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele. Birth Defects Res A Clin Mol Teratol. 2010;88:689-94 pubmed publisher
    ..Periconceptional folic acid supplementation is a modifier of MM risk in humans, leading toan interest in the folate transport genes as potential candidates for association to MM...
  53. Zhao W, Yue L, Chen X. [Association of single nucleotide polymorphism of reduced folate carrier gene with susceptibility to acute leukemia]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2011;28:446-9 pubmed publisher
    To investigate the allele and genotype frequencies of reduced folate carrier gene (RFC) 80G/A polymorphism in Chinese patients with acute leukemia (AL) and healthy control children, and to provide clue for association between the single ..
  54. Shaw G, Lammer E, Zhu H, Baker M, Neri E, Finnell R. Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida. Am J Med Genet. 2002;108:1-6 pubmed
    ..We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1)...
  55. Kumari P, Ali A, Sukla K, Singh S, Raman R. Lower incidence of nonsyndromic cleft lip with or without cleft palate in females: is homocysteine a factor?. J Biosci. 2013;38:21-6 pubmed
    ..association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and SLC19A1 (RFC1) G80A genotypes from an eastern Indian cohort to investigate whether Hcy and other Hcy-pathway genes also ..
  56. Lima A, Bernardes M, Azevedo R, Monteiro J, Sousa H, Medeiros R, et al. SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. Toxicol Sci. 2014;142:196-209 pubmed publisher
  57. Dufficy L, Naumovski N, Ng X, Blades B, Yates Z, Travers C, et al. G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population. Life Sci. 2006;79:957-66 pubmed
    The functional consequences of the G80A RFC SNP on the expressed reduced folate carrier protein were evaluated by looking at the relationship between intake of folate, plasma folate and cellular stores of the vitamin...
  58. Chancy C, Kekuda R, Huang W, Prasad P, Kuhnel J, Sirotnak F, et al. Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium. J Biol Chem. 2000;275:20676-84 pubmed
    ..This constitutes the first report of the differential polarization of the two folate transport proteins in any polarized epithelium. ..
  59. Ifergan I, Meller I, Issakov J, Assaraf Y. Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer. 2003;98:1958-66 pubmed
    ..Although MTX uptake proceeds primarily through the reduced folate carrier (RFC) protein and efflux occurs via multidrug resistance protein 1 (MRP1), RFC protein expression in ..
  60. Wang S, Sun L, Zeng W, Wu W, Zhang G. Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia. Med Oncol. 2014;31:62 pubmed publisher
    ..Rs1051296 G>T was associated with MTX plasma concentration, suggesting that miRNAs might be involved in the post-transcriptional regulation of SLC19A1. ..
  61. Flintoff W, Sadlish H, Gorlick R, Yang R, Williams F. Functional analysis of altered reduced folate carrier sequence changes identified in osteosarcomas. Biochim Biophys Acta. 2004;1690:110-7 pubmed
    ..that cDNAs generated from osteosarcoma mRNA from a fraction of patients contain sequence changes in the reduced folate carrier (RFC), the membrane protein transporter for Mtx...
  62. Jang M, Kim J, Jeon Y, Chong S, Hong S, Hwang S, et al. Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population. Gene. 2014;533:558-64 pubmed publisher
    ..the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1)...
  63. Wang H, Wang J, Zhang J, Zhao L, Zhai G, Xiang Y, et al. Reduced folate carrier A80G polymorphism and susceptibility to neural tube defects: a meta-analysis. Gene. 2012;510:180-4 pubmed publisher
    The reduced folate carrier (RFC1) plays a crucial role in mediating folate delivery into a variety of cells. RFC1 polymorphism (A80G) has been reported to be associated with increased risk of neural tube defects (NTDs)...
  64. Mansoori N, Tripathi M, Alam R, Luthra K, Sharma S, Lakshmy R, et al. Serum folic acid and RFC A80G polymorphism in Alzheimer's disease and vascular dementia. Am J Alzheimers Dis Other Demen. 2014;29:38-44 pubmed publisher
    ..Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain ..
  65. Lissowska J, Gaudet M, Brinton L, Chanock S, Peplonska B, Welch R, et al. Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses. Int J Cancer. 2007;120:2696-703 pubmed
    ..In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk. ..
  66. de Lima E, da Silva V, da Silva H, Bezerra A, de Morais V, de Morais A, et al. MTR polymorphic variant A2756G and retinoblastoma risk in Brazilian children. Pediatr Blood Cancer. 2010;54:904-8 pubmed publisher
    ..reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), carrier of reduced folate 1 (RFC-1 A80G) and thymidylate synthase (TYMS 2R > 3R) altered the risk for retinoblastoma...
  67. Marchant J, Subramanian V, Parker I, Said H. Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in Mammalian epithelial cells. J Biol Chem. 2002;277:33325-33 pubmed
    ..of the water-soluble vitamin folic acid in mammalian cells is via a plasma membrane protein known as the reduced folate carrier (RFC)...
  68. 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. ..
  69. Summers C, Mitchell L, Stanislawska Sachadyn A, Baido S, Blair I, Von Feldt J, et al. Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. Birth Defects Res A Clin Mol Teratol. 2010;88:679-88 pubmed publisher
    ..smoking, B(12), and polymorphisms in MTR, TYMS, methionine synthase reductase (MTRR), and reduced folate carrier1 (RFC1)...
  70. Lau D, Flemming C, Gherardi S, Perini G, Oberthuer A, Fischer M, et al. MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma. Oncotarget. 2015;6:15510-23 pubmed
    ..We have demonstrated that methotrexate uptake in neuroblastoma cells is mediated principally by the reduced folate carrier (RFC; SLC19A1), that SLC19A1 and MYCN expression are highly correlated in both patient tumors and cell ..
  71. Lightfoot T, Skibola C, Willett E, Skibola D, Allan J, Coppede F, et al. Risk of non-Hodgkin lymphoma associated with polymorphisms in folate-metabolizing genes. Cancer Epidemiol Biomarkers Prev. 2005;14:2999-3003 pubmed
    ..hydroxymethyltransferase (SHMT1) 1420 C >T, thymidylate synthase (TYMS) 1494del6 and 28-bp repeat, and reduced folate carrier (RFC) 80 G >A. Increased risks for NHL [odds ratio (OR), 1.48; 95% confidence intervals (CI), 1.12-1...
  72. Tolner B, Roy K, Sirotnak F. Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promoters and alternatively spliced transcripts with 5' end heterogeneity. Gene. 1998;211:331-41 pubmed
    The organization and structure of the human RFC-1 gene encoding a folate transporter were determined. The RFC-1 gene spans 22...
  73. Dixon K, Lanpher B, Chiu J, Kelley K, Cowan K. A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells. J Biol Chem. 1994;269:17-20 pubmed
    ..Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017)...
  74. Rothem L, Ifergan I, Kaufman Y, Priest D, Jansen G, Assaraf Y. Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines. Biochem J. 2002;367:741-50 pubmed
    ..CCRF-CEM sublines to the novel antifolates ZD9331, GW1843, AG2034, PT523 and edatrexate, which use the reduced folate carrier (RFC) as their main cellular uptake route and that target different folate-dependent enzymes...
  75. 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. ..
  76. James S, Melnyk S, Jernigan S, Pavliv O, Trusty T, Lehman S, et al. A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1209-20 pubmed publisher
    ..In case-control analysis, a significant increase in the reduced folate carrier (RFC1) G allele frequency was found among case mothers, but not among fathers or affected children...
  77. Christensen K, Zada Y, Rohlicek C, Andelfinger G, Michaud J, Bigras J, et al. Risk of congenital heart defects is influenced by genetic variation in folate metabolism. Cardiol Young. 2013;23:89-98 pubmed publisher
    ..677C.T, MTHFR c.1298A.C, methionine synthase reductase (MTRR) c.66A.G, and reduced folate carrier (SLC19A1) c.80A...
  78. Giusti B, Saracini C, Bolli P, Magi A, Martinelli I, Peyvandi F, et al. Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism. Thromb Haemost. 2010;104:231-42 pubmed publisher
    ..This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism. ..
  79. Yang Y, Li X, Sun Q, He B, Jia Y, Cai D, et al. Folate deprivation induces cell cycle arrest at G0/G1 phase and apoptosis in hippocampal neuron cells through down-regulation of IGF-1 signaling pathway. Int J Biochem Cell Biol. 2016;79:222-230 pubmed publisher
  80. Cai C, Xiao R, Van Halm Lutterodt N, Zhen J, Huang X, Xu Y, et al. Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults. Nutrients. 2016;8: pubmed
    ..Cognition of adults was associated with MTHFR, SLC19A1 gene polymorphism and serum Hcy levels. This study clearly establishes a combined effect of MTHFR gene polymorphism and serum B vitamins levels on cognition in Chinese adults. ..
  81. Kurosawa Y, Furugen A, Nishimura A, Narumi K, Kobayashi M, Iseki K. Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells. Toxicol In Vitro. 2018;48:104-110 pubmed publisher
    ..receptor-? (FR?) and proton-coupled folate transporter (PCFT) mRNA expression; however, it did not affect reduced folate carrier expression...
  82. Liu J, Mo W, Zhang Z, Yu H, Yang A, Qu F, et al. Single Nucleotide Polymorphisms in SLC19A1 and SLC25A9 Are Associated with Childhood Autism Spectrum Disorder in the Chinese Han Population. J Mol Neurosci. 2017;62:262-267 pubmed publisher
    ..There was no significant association between genotypes and allele frequencies with the severity of the disease. Our study suggests that these genetic variants of SLC19A1 and SLC25A12 may be associated with risks for childhood ASD. ..
  83. Martino A, Mancuso T, Rossi A. Application of high-resolution melting to large-scale, high-throughput SNP genotyping: a comparison with the TaqMan method. J Biomol Screen. 2010;15:623-9 pubmed publisher
  84. Yasuda S, Hasui S, Yamamoto C, Yoshioka C, Kobayashi M, Itagaki S, et al. Placental folate transport during pregnancy. Biosci Biotechnol Biochem. 2008;72:2277-84 pubmed
    ..We found that folate receptor alpha (FRalpha) and reduced folate carrier (RFC) localized on the apical side of human placental villi...
  85. Liu X, Matherly L. Analysis of membrane topology of the human reduced folate carrier protein by hemagglutinin epitope insertion and scanning glycosylation insertion mutagenesis. Biochim Biophys Acta. 2002;1564:333-42 pubmed
    The human reduced folate carrier (RFC) is the major membrane transport system for both reduced folates and chemotherapeutic antifolate drugs, such as methotrexate (MTX)...
  86. Chatzikyriakidou A, Vakalis K, Kolaitis N, Kolios G, Naka K, Michalis L, et al. Distinct association of SLC19A1 polymorphism -43T>C with red cell folate levels and of MTHFR polymorphism 677C>T with plasma folate levels. Clin Biochem. 2008;41:174-6 pubmed
    ..SLC19A1 and MTHFR genes are differently associated with red cell and plasma folate levels. ..
  87. Kramer M, Kahn S, Rozen R, Evans R, Platt R, Chen M, et al. Vasculopathic and thrombophilic risk factors for spontaneous preterm birth. Int J Epidemiol. 2009;38:715-23 pubmed publisher
    ..5 (0.9-2.7)]. No significant associations were observed with the DNA polymorphisms or with plasma TAT or folate levels. Similar vasculopathic risk factors may underlie preterm birth and adult coronary heart disease and stroke. ..
  88. Bohanec Grabar P, Leandro García L, Inglada Pérez L, Logar D, Rodriguez Antona C, Dolzan V. Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients. Pharmacogenomics. 2012;13:1583-94 pubmed publisher
    ..Individual SNP and haplotype analyses suggest that rs1051266 could be a functional variant altering MTX toxicity; however, validation in independent studies is needed. ..
  89. Kastrup I, Worm J, Ralfkiaer E, Hokland P, Guldberg P, Grønbaek K. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma. Eur J Haematol. 2008;80:61-6 pubmed
    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX)...
  90. Payton S, Whetstine J, Ge Y, Matherly L. Transcriptional regulation of the human reduced folate carrier promoter C: synergistic transactivation by Sp1 and C/EBP beta and identification of a downstream repressor. Biochim Biophys Acta. 2005;1727:45-57 pubmed
    The human reduced folate carrier (hRFC) is ubiquitously but differentially expressed in human tissues and its levels are regulated by up to six alternatively spliced non-coding regions (designated A1/A2, A, B, C, D, and E) and by at least ..
  91. Giusti B, Sestini I, Saracini C, Sticchi E, Bolli P, Magi A, et al. High-throughput multiplex single-nucleotide polymorphism (SNP) analysis in genes involved in methionine metabolism. Biochem Genet. 2008;46:406-23 pubmed publisher
    ..2% concordance. We also performed a haplotype analysis. This approach could represent a useful tool to investigate the genotype-phenotype correlation and the association of these genes with hyperhomocysteinemia and correlated diseases. ..