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FLASH GENE
Symbol MTHFR contributors: SGE - updated : 29-07-2010
HGNC name methylenetetrahydrofolate reductase (NAD(P)H)
HGNC id 7436
Corresponding disease
MTHFR developmental delay
NTDS1 neural tube defects, folate- sensitive
Location 1p36.22      Physical location : 11.845.786 - 11.866.160
Synonym name 5,10-methylenetetrahydrofolate reductase (NADPH)
EC.number 1.5.1.20
DNA
TYPE functioning gene
STRUCTURE 20.33 kb     12 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure CpG islands, numerous consensus sequences transcription factor binding sites (SP1 binding sites) (Gaughan 2000)
MAPPING cloned Y linked N status provisional
Physical map
FLJ37118 1p36.22 hypothetical protein FLJ37118 LOC390996 1 similar to Cofilin, non-muscle isoform TARDBP 1p36.22 TAR DNA binding protein AF311304 1p36.22 hypothetical protein AF311304 MASP2 1p36.3-p36.2 mannan-binding lectin serine protease 2 SRM 1p36-p22 spermidine synthase PMSCL2 1p36.22 polymyositis/scleroderma autoantigen 2, 100kDa FRAP1 1p36.3-p36.2 FK506 binding protein 12-rapamycin associated protein 1 CDT6 1p36.3-p36.2 angiopoietin-like factor TERE1 1p36 angiopoietin-like factor KIAA1337 1p36.21 KIAA1337 protein FBXO2 1p36.21 F-box only protein 2 FBX30 1p36.21 F-box protein FBX30 FBXO6 1p36.23-p36.11 F-box only protein 6 MAD2L2 1p36 MAD2 mitotic arrest deficient-like 2 (yeast) LOC374946 1p36.21 hypothetical gene supported by AK075558; BC021286 AGTRAP 1p36.21 angiotensin II receptor-associated protein DKFZp434E1410 1p36.21 hypothetical protein DKFZp434E1410 MTHFR 1p36.3 5,10-methylenetetrahydrofolate reductase (NADPH) CLCN6 1p36.2 chloride channel 6 NPPA 1p36.2 natriuretic peptide precursor A NPPB 1p36.2 natriuretic peptide precursor B LOC390997 1 similar to SET binding factor 1 isoform a; myotubularin-related protein 5 MGC33867 1p36.21 hypothetical protein MGC33867 PLOD 1p36.31 procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI) MFN2 1p36.21 mitofusin 2 FLJ12438 1p36.21 hypothetical protein FLJ12438 TNFRSF8 1p36 tumor necrosis factor receptor superfamily, member 8 TNFRSF1B 1p36.32 tumor necrosis factor receptor superfamily, member 1B LOC390998 1 similar to 60S ribosomal protein L10 (QM protein) (Tumor suppressor QM) (Laminin receptor homolog) FLJ10619 DHRS3 1p36.1 dehydrogenase/reductase (SDR family) member 3
RNA
TRANSCRIPTS type messenger
text three major transcripts different initiation sites, two additional spliced variants of form 1
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
12 - 7150 - 656 - Goyette (1998)
  • MTHFRS
  • - polyA site 9800 - - - Gaughan (2000)
    also called MTHFRL
    - polyA site 7200 - - - Gaughan (2000)
    also called MTHFRM
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach    
    Lymphoid/Immunelymph node   highly
     spleen   highly
    Nervousbrain    
    Reproductivefemale systemplacenta   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal catalytic domain
  • secondary structure FAD moncovalently bound
    conjugated FlavoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Mthfr (90.8pc)
    homolog to rattus Mthfr (89.1pc)
    Homologene
    FAMILY
  • methylenetetrahydrofolate reductase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • reducing 5-10 methylene THF to 5 methyl-THF for methionine biosynthesis (oxydoreductase)
  • playing a role in DNA methylation, synthesis, and repair (Yuan 2007)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism aminoacid
    signaling
    folate metabolism, methionine biosynthesis
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • NADPH
  • FAD
  • protein
    cell & other
    REGULATION
    Other allosterically regulated by S-adenosylmethionine
    ASSOCIATED DISORDERS
    corresponding disease(s) MTHFR , NTDS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    may protect against the development of hepatocellular carcinoma (Yuan 2008)
    Susceptibility
  • to schizophrenia (rs801131)
  • to increased mortality risk in men in middle and old age
  • to recurrent abortus in early pregnancy
  • to cardiovascular disease (CAD)
  • Variant & Polymorphism SNP , other
  • common variant putatively involved in occlusive vascular disease, neural tube defects, colon cancer and adult acute leukemia, cardiovascular disease, 677CT/1298CC or 677TT/1298CC genotypes, 677CT/1298AC
  • polymorphisms increasing mortality risk in men in middle and old age
  • maternal polymorphisms 677C-T and 1298A-C of MTHFR and risk for Down syndrome
  • TT genotype was associated with an increased risk of CAD
  • polymorphism associated with risk of metabolic syndrome in patients with schizophrenia (Van Winkel 2010)
  • SNp is associated with blood pressure and/or hypertension in the Japanese (Takeuchi 2010)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS