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MTHFD1 Gene

protein-coding   GIFtS: 68
GCID: GC14P064854

Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent)...


(Previous symbols: MTHFC, MTHFD)
  See MTHFD1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Methylenetetrahydrofolate Dehydrogenase (NADP+ Dependent) 1,
Methenyltetrahydrofolate Cyclohydrolase, Formyltetrahydrofolate
Synthetase1 2
     5,10-Methylenetetrahydrofolate Dehydrogenase,
5,10-Methylenetetrahydrofolate Cyclohydrolase, 10-Formyltetrahydrofolate
Synthetase2
MTHFC1 2 3 5     C-1-Tetrahydrofolate Synthase, Cytoplasmic2
MTHFD1 2 3 5     Cytoplasmic C-1-Tetrahydrofolate Synthase2
C1-THF Synthase2 3     EC 6.3.4.38

External Ids:    HGNC: 74321   Entrez Gene: 45222   Ensembl: ENSG000001007147   OMIM: 1724605   UniProtKB: P115863   

Export aliases for MTHFD1 gene to outside databases

Previous GC identifers: GC14P062182 GC14P058648 GC14P062845 GC14P063924 GC14P045027


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for MTHFD1 Gene:
This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate
dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of
these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of
tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The
trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the
dehydrogenase and cyclohydrolase activities and a larger synthetase domain. (provided by RefSeq, Jul 2008)

GeneCards Summary for MTHFD1 Gene:
MTHFD1 (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase) is a protein-coding gene. Diseases associated with MTHFD1 include total spina bifida aperta, and thoracolumbosacral spina bifida cystica. GO annotations related to this gene include methylenetetrahydrofolate dehydrogenase (NADP+) activity and formate-tetrahydrofolate ligase activity. An important paralog of this gene is MTHFD2.

Gene Wiki entry for MTHFD1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000014.8  NC_018925.2  NT_026437.13  
Regulatory elements:
   Regulatory transcription factor binding sites in the MTHFD1 gene promoter:
         RFX1   NF-YA   NF-YC   STAT5A   CBF-C   NF-YB   HOXA5   CP1A   CP1C   NF-Y   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMTHFD1 promoter sequence
   Search Chromatin IP Primers for MTHFD1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MTHFD1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 14q24   Ensembl cytogenetic band:  14q23.3   HGNC cytogenetic band: 14q24

MTHFD1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MTHFD1 gene location

GeneLoc information about chromosome 14         GeneLoc Exon Structure

GeneLoc location for GC14P064854:  view genomic region     (about GC identifiers)

Start:
64,854,749 bp from pter      End:
64,926,725 bp from pter
Size:
71,977 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586 (See protein sequence)
Recommended Name: C-1-tetrahydrofolate synthase, cytoplasmic  
Size: 935 amino acids; 101559 Da
Subunit: Homodimer
4 PDB 3D structures from and Proteopedia for MTHFD1:
1A4I (3D)        1DIA (3D)        1DIB (3D)        1DIG (3D)    
Secondary accessions: B2R5Y2 G3V2B8 Q86VC9 Q9BVP5

Explore the universe of human proteins at neXtProt for MTHFD1: NX_P11586

Explore proteomics data for MTHFD1 at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys58, Lys150, Lys354, Lys370, Lys473, Lys543, Lys588, Lys684, Lys784, Lys819
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for MTHFD1 (P11586) (see all 21)
     PICMAKT  GGGYSQV  LMQTLEG  NLHLTGD 


    See MTHFD1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005947.3  
    ENSEMBL proteins: 
     ENSP00000438588   ENSP00000450560   ENSP00000477359   ENSP00000477501   ENSP00000216605  
     ENSP00000476468   ENSP00000477199  
    Reactome Protein details: P11586

    MTHFD1 Human Recombinant Protein Products:

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    Cloud-Clone Corp. Proteins for MTHFD1

     
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    antibodies-online proteins for MTHFD1 (2 products) 

     
    antibodies-online peptides for MTHFD1

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    antibodies-online antibodies for MTHFD1 (19 products) 

    MTHFD1 Assay Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 8):
     IPR020631 THF_DH/CycHdrlase_NAD-bd_dom
     IPR020628 Formate_THF_ligase_CS
     IPR027417 P-loop_NTPase
     IPR020630 THF_DH/CycHdrlase_cat_dom
     IPR020867 THF_DH/CycHdrlase_CS

    Graphical View of Domain Structure for InterPro Entry P11586

    ProtoNet protein and cluster: P11586

    2 Blocks protein domains:
    IPB000559 Formate-tetrahydrofolate ligase
    IPB000672 Tetrahydrofolate dehydrogenase/cyclohydrolase


    UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586
    Domain: This trifunctional enzyme consists of two major domains: an N-terminal part containing the methylene-THF
    dehydrogenase and cyclohydrolase activities and a larger C-terminal part containing formyl-THF synthetase
    activity
    Similarity: In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family
    Similarity: In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family


    Find genes that share domains with MTHFD1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: C1TC_HUMAN, P11586
    Catalytic activity: 5,10-methylenetetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
    Catalytic activity: 5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate
    Catalytic activity: ATP + formate + tetrahydrofolate = ADP + phosphate + 10-formyltetrahydrofolate

         Genatlas biochemistry entry for MTHFD1:
    folate dependent,trifunctional enzyme catalyzing the oxidation of 5 methy THF for use in purine biosynthesis(see
    THFC,THFD,THFS)

         Enzyme Number (IUBMB): EC 6.3.4.32

         Gene Ontology (GO): Selected molecular function terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003824catalytic activity ----
    GO:0004329formate-tetrahydrofolate ligase activity TAS--
    GO:0004477methenyltetrahydrofolate cyclohydrolase activity TAS--
    GO:0004486methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity TAS--
    GO:0004488methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA--
         
    Find genes that share ontologies with MTHFD1           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for MTHFD1:
     Increased gamma-H2AX phosphory 

         11 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Mthfd1):
     cardiovascular system  cellular  embryogenesis  growth/size/body  hematopoietic system 
     homeostasis/metabolism  immune system  limbs/digits/tail  mortality/aging  nervous system 
     other 

    Find genes that share phenotypes with MTHFD1           About GenesLikeMe

    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for MTHFD1

    miRNA
    Products:
        
    miRTarBase miRNAs that target MTHFD1:
    hsa-let-7a-5p (MIRT052561), hsa-mir-17-3p (MIRT050788), hsa-mir-193b-3p (MIRT016506), hsa-mir-106b-5p (MIRT044374), hsa-mir-324-5p (MIRT043098), hsa-mir-744-5p (MIRT037507), hsa-mir-877-5p (MIRT037267)

    Block miRNA regulation of human, mouse, rat MTHFD1 using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate MTHFD1:
    hsa-miR-942 hsa-miR-32* hsa-miR-1207-5p
    SwitchGear 3'UTR luciferase reporter plasmidMTHFD1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat MTHFD1

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    GenScript: all cDNA clones in your preferred vector: MTHFD1 (NM_005956)
    Browse Sino Biological Human cDNA Clones
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MTHFD1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    C1TC_HUMAN, P11586: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    mitochondrion4

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm ----
    GO:0005739mitochondrion IEA--
    GO:0005829cytosol TAS--
    GO:0070062extracellular vesicular exosome IDA19056867

    Find genes that share ontologies with MTHFD1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for MTHFD1 About   (see all 6)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1One carbon pool by folate
    One carbon pool by folate0.53
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics0.34
    One Carbon Metabolism0.53
    tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate0.00
    Trans-sulfuration and one carbon metabolism0.43
    Antimetabolite Pathway - Folate Cycle, Pharmacodynamics0.00
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.35
    2Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    3Defective BTD causes biotidinase deficiency
    Defective BTD causes biotidinase deficiency1.00
    Metabolism of vitamins and cofactors1.00
    Defective AMN causes hereditary megaloblastic anemia 11.00
    Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC1.00
    Defective MMAA causes methylmalonic aciduria type cblA1.00
    Defective MUT causes methylmalonic aciduria mut type1.00
    Defective CD320 causes methylmalonic aciduria1.00
    Defects in cobalamin (B12) metabolism1.00
    4folate polyglutamylation
    folate polyglutamylation0.50
    folate transformations0.43
    5histidine degradation III
    histidine degradation III


    Find genes that share SuperPaths with MTHFD1           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    Selected BioSystems Pathways for MTHFD1 (see all 6)
        One Carbon Metabolism
    histidine degradation III
    folate transformations
    folate polyglutamylation
    tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate

    1 Reactome Pathway for MTHFD1
        Metabolism of folate and pterines

    3 PharmGKB Pathways for MTHFD1
        Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

    2 Kegg Pathways  (Kegg details for MTHFD1):
        One carbon pool by folate
    Metabolic pathways

    UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586
    Pathway: One-carbon metabolism; tetrahydrofolate interconversion

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for MTHFD1
    Interactions:

        Search GeneGlobe Interaction Network for MTHFD1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for MTHFD1 (P115861, 2, 3 ENSP000002166054) via UniProtKB, MINT, STRING, and/or I2D (see all 251)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    WRAP73Q9P2S51, 3, ENSP000002707084EBI-709638,EBI-1054904 I2D: score=2 STRING: ENSP00000270708
    HSP90AB1P082382, 3MINT-72655 I2D: score=3 
    PRPF6O949062, 3MINT-8173832 I2D: score=3 
    MCCP235081, 3EBI-709638,EBI-307531 I2D: score=2 
    TRAF6Q9Y4K31, 3EBI-709638,EBI-359276 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000105histidine biosynthetic process IEA--
    GO:0006164purine nucleotide biosynthetic process IEA--
    GO:0006730one-carbon metabolic process IBA--
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--

    Find genes that share ontologies with MTHFD1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MTHFD1 (C1TC)

    Selected HMDB Compounds for MTHFD1 (see all 12)    About this table
    CompoundSynonyms CAS #PubMed Ids
    5,10-Methenyltetrahydrofolic acid5,10-Methenyltetrahydrofolate (see all 13)7444-29-3--
    5,10-Methylene-THF5,10-methylene-THF (see all 8)31690-11-6--
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    Formic acidAdd-F (see all 21)64-18-6--
    NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--
    NADH1,4-Dihydronicotinamide adenine dinucleotide (see all 17)58-68-4--
    NADPAdenine-nicotinamide dinucleotide phosphate (see all 18)53-59-8--
    NADPH2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)53-57-6--
    PhosphateNFB Orthophosphate (see all 13)14265-44-2--

    5 DrugBank Compounds for MTHFD1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Tetrahydrofolic acid5,6,7,8-tetrahydrofolate (see all 3)135-16-0targetcofactor12937168 12949177 11323021 16171773 17533396
    2'-Monophosphoadenosine 5'-Diphosphoribose-- --target--17139284 17016423
    LY249543-- --target--17139284 17016423
    LY374571-- --target--17139284 17016423
    NADHbeta-DPNH (see all 18)606-68-8target--17139284 17016423

    Selected Novoseek inferred chemical compound relationships for MTHFD1 gene (see all 13)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    5,10-methenyltetrahydrofolate 96.5 20 9701462 (1), 18801628 (1), 18804703 (1), 19649727 (1) (see all 16)
    10-formyltetrahydrofolate 91.7 8 16171773 (1), 18801628 (1), 19649727 (1), 16712703 (1) (see all 7)
    folate 81.5 43 17438114 (2), 19167960 (2), 12482398 (1), 19020309 (1) (see all 15)
    ch2h4folate 76.8 1 16171773 (1)
    cystathionine 74.4 3 15503105 (1), 19112534 (1)
    homocysteine 71.1 19 17438114 (4), 9701462 (1), 20374669 (1), 15503105 (1) (see all 6)
    methionine 70.9 19 19020309 (1), 16712703 (1), 17449906 (1), 20209990 (1) (see all 9)
    purine 57.8 2 18767138 (1)
    thymidylate 54.9 5 19020309 (1), 17449906 (1), 15797993 (1), 15953655 (1)
    cobalamin 51.3 1 2335231 (1)

    1 PharmGKB related drug/compound annotation for MTHFD1 gene    About this table
    Drug/compound PharmGKB Annotation
    methotrexateCA  



    Find genes that share compounds with MTHFD1           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MTHFD1 gene: 
    NM_005956.3  

    Unigene Cluster for MTHFD1:

    Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
    Hs.652308  [show with all ESTs]
    Unigene Representative Sequence: NM_005956
    16 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000545908(uc010aqe.2) ENST00000555709(uc001xhb.3 uc010aqf.3)
    ENST00000554739 ENST00000554768 ENST00000555252 ENST00000216605 ENST00000557539
    ENST00000554057 ENST00000553391 ENST00000554677 ENST00000555858 ENST00000556771
    ENST00000553405 ENST00000556284 ENST00000557370 ENST00000554353
    miRNA
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    3 qRT-PCR Assays for microRNAs that regulate MTHFD1:
    hsa-miR-942 hsa-miR-32* hsa-miR-1207-5p
    SwitchGear 3'UTR luciferase reporter plasmidMTHFD1 3' UTR sequence
    Inhib. RNA
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      QuantiTect SYBR Green Assays in human, mouse, rat MTHFD1
      QuantiFast Probe-based Assays in human, mouse, rat MTHFD1

    Additional mRNA sequence: 

    AK095514.1 AK097323.1 AK302747.1 AK309266.1 AK312361.1 BC001014.2 BC009806.2 BC050420.1 
    J04031.1 

    22 DOTS entries:

    DT.447175  DT.100884819  DT.40278922  DT.75113598  DT.102843121  DT.95076849  DT.100758571  DT.120751953 
    DT.98082896  DT.100030488  DT.100884815  DT.121299659  DT.121299672  DT.121299676  DT.100659065  DT.100884822 
    DT.120752066  DT.40210775  DT.95076882  DT.75104387  DT.92450985  DT.95295841 

    Selected AceView cDNA sequences (see all 389):

    BE741343 BG675843 BQ267460 BQ921397 BC050420 BM839882 CR613709 CR601328 
    BQ430626 BM765529 BG260447 BM836348 BQ052407 BQ646183 BQ057781 CB162544 
    CR614604 CB122415 BM765628 BU553283 BM765617 BP383185 BM764452 BQ333802 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MTHFD1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TCTGTTTACT
    MTHFD1 Expression
    About this image


    MTHFD1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Brain (Nervous System)    fully expand to see all 7 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Membranous Facial Bones
     
     Liver (Hepatobiliary System)
             Hepatocytes Liver Lobule
    MTHFD1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MTHFD1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.652308

    UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586
    Tissue specificity: Ubiquitous

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for MTHFD1 gene from Selected species (see all 27)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Mthfd11 , 5 methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthase less1, 5 87.27(n)1
    93.16(a)1
      12 (33.52 cM)5
    1081561  NM_138745.21  NP_620084.21 
     762552325 
    chicken
    (Gallus gallus)
    Aves MTHFD11 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase less 75.83(n)
    80.86(a)
      423508  NM_001039303.1  NP_001034392.1 
    lizard
    (Anolis carolinensis)
    Reptilia MTHFD16
    methylenetetrahydrofolate dehydrogenase (NADP+ dep...
    81(a)
    1 ↔ 1
    1(1471047-1557802)
    African clawed frog
    (Xenopus laevis)
    Amphibia mthfd1-prov2 C1-tetrahydrofolate synthase 76.07(n)    BC045019.1 
    zebrafish
    (Danio rerio)
    Actinopterygii mthfd12 methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofola less 74.63(n)   260441  BC045396.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta pug1 , 3 methylenetetrahydrofolate
    dehydrogenase (NADP+) less3
    pugilist1
    61(a)3
    60.06(n)1
    61.35(a)1
      86C43
    412791  NM_169350.21  NP_731489.21 
    worm
    (Caenorhabditis elegans)
    Secernentea K07E3.4b3
    K07E3.41
    K07E3.41 70(a)
    (best of 3)3
    64.03(n)1
    70.62(a)1
      X(8116261-8119149)3
    1810641  NM_076959.51  NP_509360.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MIS1(YBR084W)4
    ADE31
    Mitochondrial C1-tetrahydrofolate synthase, involved in interconversion between different oxidation states of tetrahydrofolate (THF); provides activities of formyl-THF synthetase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase less4
    ADE31
    58.17(n)1
    59.07(a)1
      2(411054-413981)4
    8531181  NP_011720.31  8523784 
     NP_009640.14 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons THFS1 THFS 61.49(n)
    67.63(a)
      841470  NM_103931.3  NP_564571.1 
    rice
    (Oryza sativa)
    Liliopsida Os09g04468001 Os09g0446800 60.42(n)
    68.27(a)
      4347204  NM_001069845.1  NP_001063310.1 


    ENSEMBL Gene Tree for MTHFD1 (if available)
    TreeFam Gene Tree for MTHFD1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MTHFD1 gene
    MTHFD22  MTHFD2L2  MTHFD1L2  
    4 SIMAP similar genes for MTHFD1 using alignment to 6 protein entries:     C1TC_HUMAN (see all proteins):
    bA251O17.4    MTHFD1L    MTHFD2    MTHFD2L

    Find genes that share paralogs with MTHFD1           About GenesLikeMe


    2 Pseudogenes.org Pseudogenes for MTHFD1
    PGOHUM00000245259 PGOHUM00000261943


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MTHFD1 (see all 1541)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 14 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs341811101,2,,4
    C,Fother145879140(+) CAAGCG/ATTTCC 2 /H /R mis15Minor allele frequency- A:0.00NA EU 5607
    rs22362251,2,,4
    C,F,O,A,Hother145895507(-) CGATCC/TGGTCT 2 Q R mis1 ese331Minor allele frequency- N:0.00EA NA NS CSA WA EU 8917
    rs1836998541,2
    --45839416(+) CAACTC/TATACA 1 -- us2k10--------
    rs19565451,2
    C,F,A,H--45839559(-) ATCCCA/GTTTTA 1 -- us2k133Minor allele frequency- G:0.18NS EA NA WA CSA 2988
    rs1878787451,2
    --45839671(+) CCTTCA/CATTTT 1 -- us2k10--------
    rs1914740621,2
    --45839705(+) TACAAC/TACAAT 1 -- us2k10--------
    rs1416224611,2
    --45839721(+) ACAATA/GTGTTT 1 -- us2k10--------
    rs1822328871,2
    --45839815(+) TAAGGC/TCACGC 1 -- us2k10--------
    rs1157237651,2
    F--45839839(+) CCCATT/CATCCC 1 -- us2k11Minor allele frequency- C:0.01WA 118
    rs732718751,2
    C,F--45840022(+) CAGAGG/CCTACA 1 -- us2k11Minor allele frequency- C:0.50WA 2

    HapMap Linkage Disequilibrium report for MTHFD1 (64854749 - 64926725 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for MTHFD1:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2670925CNV Deletion23128226
    esv2748779CNV Deletion23290073
    nsv902019CNV Gain21882294
    nsv902022CNV Gain21882294

    Human Gene Mutation Database (HGMD): MTHFD1
    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing MTHFD1
    DNA2.0 Custom Variant and Variant Library Synthesis for MTHFD1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 172460   
    OMIM disorders: 601634  
    UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586
  • Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida
    (myelomeningocele) and anencephaly. Note=Disease susceptibility is associated with variations affecting the gene
    represented in this entry
  • Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from
    the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with
    progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon
    and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=Disease
    susceptibility may be associated with variations affecting the gene represented in this entry

  • 14 diseases for MTHFD1:    
    About MalaCards
    total spina bifida aperta    thoracolumbosacral spina bifida cystica    cervical spina bifida cystica    lumbosacral spina bifida cystica
    cervicothoracic spina bifida aperta    upper thoracic spina bifida aperta    lumbosacral spina bifida aperta    cervicothoracic spina bifida cystica
    cervical spina bifida aperta    upper thoracic spina bifida cystica    total spina bifida cystica    thoracolumbosacral spina bifida aperta
    spina bifida    neural tube defects


    Find genes that share disorders with MTHFD1           About GenesLikeMe

    3 Novoseek inferred disease relationships for MTHFD1 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    neural tube defects 75.9 6 19130090 (2), 9611072 (1), 18767138 (1)
    lymphoblastic leukemia acute childhood 56.8 1 14647408 (1)
    spina bifida 44.4 1 17894836 (1)

    Genetic Association Database (GAD): MTHFD1
    Human Genome Epidemiology (HuGE) Navigator: MTHFD1 (94 documents)

    Export disorders for MTHFD1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for MTHFD1 gene, integrated from 10 sources (see all 181):
    (articles sorted by number of sources associating them with MTHFD1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. (PubMed id 18767138)1, 2, 4, 9 Christensen K.E.... Rozen R. (Hum. Mutat. 2009)
    2. Confirmation of the R653Q polymorphism of the trifunctional C1- synthase enzyme as a maternal risk for neural tube defects in the Irish population. (PubMed id 16552426)1, 2, 4, 9 Parle-McDermott A....Scott J.M. (Eur. J. Hum. Genet. 2006)
    3. 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 Defects Research Group. (PubMed id 12384833)1, 2, 4, 9 Brody L.C....Swanson D.A. (Am. J. Hum. Genet. 2002)
    4. Prognostic significance of folate metabolism polymorphisms for lung cancer. (PubMed id 17533396)1, 4, 7, 9 Matakidou A....Houlston R.S. (Br. J. Cancer 2007)
    5. Primary structure of a human trifunctional enzyme. Isolation of a cDNA encoding methylenetetrahydrofolate dehydrogenase- methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase. (PubMed id 3053686)1, 2, 3 Hum D.W.... Mackenzie R.E. (J. Biol. Chem. 1988)
    6. Polymorphisms of MTHFD, plasma homocysteine levels, and risk of gastric cancer in a high-risk Chinese population. (PubMed id 17438114)1, 4, 9 Wang L....Shen H. (Clin. Cancer Res. 2007)
    7. The MTHFD1 gene is not involved in cleft lip with or without palate onset among the Italian population. (PubMed id 18261183)1, 4, 9 Palmieri A....Carinci F. (Ann. Hum. Genet. 2008)
    8. Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects. (PubMed id 9611072)1, 2, 9 Hol F.A.... Blom H.J. (Clin. Genet. 1998)
    9. Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted. (PubMed id 19167960)1, 4, 9 Ivanov A....Caudill M.A. (J Am Diet Assoc 2009)
    10. Analysis of the MTHFD1 promoter and risk of neural tube defects. (PubMed id 19130090)1, 4, 9 Carroll N....Parle-McDermott A. (Hum. Genet. 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4522 HGNC: 7432 AceView: MTHFD1 Ensembl:ENSG00000100714 euGenes: HUgn4522
    ECgene: MTHFD1 Kegg: 4522 H-InvDB: MTHFD1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for MTHFD1 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MTHFD1 gene:
    Search GeneIP for patents involving MTHFD1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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