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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

MTHFD1 Gene

protein-coding   GIFtS: 65
GCID: GC14P064854

methylenetetrahydrofolate dehydrogenase (NADP+ dependent)...


(Previous symbols: MTHFC, MTHFD)
 Explore 57 diseases affiliated with
MTHFD1 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for MTHFD1    

Aliases
for MTHFD1 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
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


Summaries
for MTHFD1 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for MTHFD1:
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)

Gene Wiki entry for MTHFD1


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000014.8  NC_018925.1  NT_026437.12  
Regulatory elements:
   SABiosciences 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 plasmid: MTHFD1 promoter sequence
   Search SABiosciences Chromatin IP Primers for MTHFD1

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for MTHFD1 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586 (See protein sequence)
Recommended Name: C-1-tetrahydrofolate synthase, cytoplasmic  
Size: 935 amino acids; 101559 Da
Subunit: Homodimer
Subcellular location: Cytoplasm
4 PDB 3D structures from and Proteopedia for MTHFD1:
1A4I (3D)        1DIA (3D)        1DIB (3D)        1DIG (3D)    
Secondary accessions: B2R5Y2 Q86VC9 Q9BVP5

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

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P11586

    • 4/21 DME Specific Peptides for MTHFD1 (P11586) (see all 21)
     PICMAKT  GGGYSQV  LMQTLEG  NLHLTGD 

    MTHFD1 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_005947.3  
    ENSEMBL proteins: 
     ENSP00000438588   ENSP00000216605   ENSP00000451309   ENSP00000450560  
    Reactome Protein details: P11586
    Human Recombinant Protein Products: 
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    Novus Biologicals MTHFD1 Protein
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    Uscn Proteins for MTHFD1

    Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA--
    GO:0005739mitochondrion TAS3528153
    GO:0005829cytosol TAS--


    MTHFD1 for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for MTHFD1

    Protein Domains /
    Families
    for MTHFD1 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    MTHFD1 for domains           About GeneDecksing

    5/7 InterPro domains/families (see all 7):
     IPR020631 THF_DH/CycHdrlase_NAD-bd_dom
     IPR020628 Formate_THF_ligase_CS
     IPR016040 NAD(P)-bd_dom
     IPR000672 THF_DH/CycHdrlase
     IPR020630 THF_DH/CycHdrlase_cat_dom

    Graphical View of Domain Structure for InterPro Entry P11586

    ProtoNet protein and cluster: P11586

    2 Blocks protein families:
    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


    Function
    for MTHFD1 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         UniProtKB/Swiss-Prot: 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

    miRNA
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    hsa-miR-942 hsa-miR-32* hsa-miR-1207-5p
    SwitchGear 3'UTR luciferase reporter plasmid: MTHFD1 3' UTR sequence
    Inhib. RNA
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    OriGene shRNA RFP: MTHFD1
    OriGene siRNA: MTHFD1
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MTHFD1

    Gene Editing
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    Clone
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    In Situ Assay
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    Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004329formate-tetrahydrofolate ligase activity TAS--
    GO:0004477methenyltetrahydrofolate cyclohydrolase activity TAS--
    GO:0004486methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity TAS--
    GO:0004488methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA--
    GO:0005524ATP binding IEA--


    MTHFD1 for ontologies           About GeneDecksing


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

    Animal Models:
         3 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Mthfd1):
     growth/size  homeostasis/metabolism  mortality/aging 

    MTHFD1 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for MTHFD1 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/7 super-pathways (see all 7) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    		Antimetabolite Pathway - Folate Cycle, Pharmacodynamics1.00
    		Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics0.36
    		Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.45
    2glycine biosynthesis I
    		folate polyglutamylation0.50
    		Metabolism of folate and pterines0.10
    		folate transformations I0.33
    3Metabolism
    		Metabolism1.00
    		Metabolic pathways0.38
    4One Carbon Metabolism
    		One Carbon Metabolism1.00
    		One carbon pool by folate0.52
    5Vitamin B5 (pantothenate) metabolism
    		Metabolism of vitamins and cofactors0.21
    		Metabolism of water-soluble vitamins and cofactors0.21

    Pathway sources
    See GeneCards unified pathways
    Show all pathways


    5 BioSystems Pathways for MTHFD1 
        One Carbon Metabolism
    histidine degradation III
    tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate
    folate polyglutamylation
    folate transformations I

    4        Reactome Pathways for MTHFD1
        Metabolism of folate and pterines
    Metabolism
    Metabolism of vitamins and cofactors
    Metabolism of water-soluble vitamins and cofactors

    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


    MTHFD1 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for MTHFD1

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

    5/198 Interacting proteins for MTHFD1 (P115861, 2, 3 ENSP000002166054) via UniProtKB, MINT, STRING, and/or I2D (see all 198)

    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): 5/11 biological process terms (GO ID links to tree view) (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000105histidine biosynthetic process IEA--
    GO:0006164purine nucleotide biosynthetic process IEA--
    GO:0006548histidine catabolic process ----
    GO:0006730one-carbon metabolic process IBA--
    GO:0006766vitamin metabolic process TAS--


    MTHFD1 for ontologies           About GeneDecksing



    Drugs & Compounds
    for MTHFD1 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    MTHFD1 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for MTHFD1

    10/12 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

    10/13 Novoseek 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
    Drug/compound PharmGKB Annotation
    methotrexateCA  
    About this table

    Search CenterWatch for drugs/clinical trials and news about MTHFD1 / C1TC 

    Transcripts
    for MTHFD1 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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
    17 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000545908(uc010aqe.2) ENST00000216605 ENST00000554739 ENST00000554768
    ENST00000555252 ENST00000557539 ENST00000554057 ENST00000553391 ENST00000556025
    ENST00000554677 ENST00000555858 ENST00000556771 ENST00000553405 ENST00000556284
    ENST00000557370 ENST00000554353 ENST00000555709(uc001xhb.3 uc010aqf.3)


    miRNA
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    hsa-miR-942 hsa-miR-32* hsa-miR-1207-5p
    SwitchGear 3'UTR luciferase reporter plasmid: MTHFD1 3' UTR sequence
    Inhib. RNA
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    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MTHFD1 (see all 7)
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    Clone
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    Primer
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    Additional cDNA 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 

    24/389 AceView cDNA sequences (see all 389):

    AI308940 BE873526 BU521318 CK825448 CB149881 BQ921397 BE906447 CB124895 
    BM765529 AI262978 BE741343 BC050420 BM833899 CR613709 BU619641 BG675843 
    AU134663 BQ267460 BQ430626 CR619741 BM549962 CR601328 J04031 BU150148 

    GeneLoc Exon Structure


    Expression
    for MTHFD1 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    MTHFD1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: TCTGTTTACT

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    MTHFD1 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    1 LifeMap In Vivo Development Anatomical Compartment/Cell 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Neural TubeMesencephalic Ventricular ZoneNeural Tube
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See MTHFD1 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MTHFD1

    SOURCE GeneReport for Unigene cluster: Hs.652308

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

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    Orthologs
    for MTHFD1 gene

    (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)
    About This Section
    This gene was present in the common ancestor of eukaryotes.

    Orthologs for MTHFD1 gene from 10/38 species (see all 38)    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
    		 --
    		 80(a)
    		 1 ↔ 1
    		 1(1506235-1557831)
    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 K07E3.4a3
    K07E3.41    		 tetrahydrofolate synthase3
    Protein K07E3.41    		 70(a)
    (best of 3)3
    64.14(n)1
    70.62(a)1    		   X(8116261-8118592)3
    1810641  NM_076960.21  NP_509361.11 
    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
    Ade3p1    		 58.28(n)1
    59.18(a)1    		   2(411054-413981)4
    8531181  NP_011720.31  8523784 
     NP_009640.14 
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons THFS1 Formate--tetrahydrofolate ligase 61.54(n)
    67.63(a)    		   841470  NM_103931.3  NP_564571.1 
    rice
    (Oryza sativa)    		 Liliopsida Os09g04468001 hypothetical protein 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
    for MTHFD1 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for MTHFD1 gene
    MTHFD1L2  LOC1009966432  
    5 SIMAP similar genes for MTHFD1 using alignment to 4 protein entries:     C1TC_HUMAN (see all proteins):
    LOC100996643    bA251O17.4    MTHFD1L    MTHFD2    MTHFD2L

    MTHFD1 for paralogs           About GeneDecksing


    2 Pseudogenes.org Pseudogenes for MTHFD1
    PGOHUM00000245259 PGOHUM00000261943


    Genomic Variants
    for MTHFD1 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1228 NCBI SNPs in MTHFD1 are shown (see all 1228)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 14 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs341811101,2
    		C,Fother64892470(+) CAAGCG/ATTTCC 2 /H /R mis15Minor allele frequency- A:0.00NA EU 5607
    rs22362251,2
    		C,F,O,A,H,other64908845(-) CGATCC/TGGTCT 2 Q R mis1 ese331Minor allele frequency- N:0.00EA NA NS CSA WA EU 8917
    rs1836998541,2
    		--64852762(+) CAACTC/TATACA 1 -- us2k10--------
    rs19565451,2
    		C,F,A,H,--64852905(-) ATCCCA/GTTTTA 1 -- us2k133Minor allele frequency- G:0.18NS EA NA WA CSA 2988
    rs1878787451,2
    		--64853017(+) CCTTCA/CATTTT 1 -- us2k10--------
    rs1914740621,2
    		--64853051(+) TACAAC/TACAAT 1 -- us2k10--------
    rs1416224611,2
    		--64853067(+) ACAATA/GTGTTT 1 -- us2k10--------
    rs1822328871,2
    		--64853161(+) TAAGGC/TCACGC 1 -- us2k10--------
    rs1157237651,2
    		--64853185(+) CCCATT/CATCCC 1 -- us2k11Minor allele frequency- C:0.01WA 118
    rs732718751,2
    		C,--64853368(+) CAGAGG/CCTACA 1 -- us2k11Minor allele frequency- C:0.50WA 2

    HapMap Linkage Disequilibrium report for MTHFD1 (64854749 - 64926725 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for MTHFD1: --
    Human Gene Mutation Database (HGMD): MTHFD1

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    Disorders / Diseases
    for MTHFD1 gene

    (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
    MTHFD1 for disorders           About GeneDecksing

    OMIM gene information: 172460   
    OMIM disorders: 601634  
    UniProtKB/Swiss-Prot: C1TC_HUMAN, P11586
  • Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD)
    • [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1
    may affect the risk of spina bifida via the maternal rather than the embryonic genotype
  • Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:114500]

    • 20/57 diseases for MTHFD1 (see all 57):    About MalaCards
    spina bifida, folate-sensitive    neural tube defect    spina bifida    cleft lip/palate
    patent ductus arteriosus    abdominal aortic aneurysm    placental abruption    cleft lip
    non-hodgkin lymphoma    type 2 diabetes mellitus    aortic aneurysm    birth defects
    orofacial cleft    congenital heart defect    leukemia/lymphoma    lymphoblastic leukemia
    systemic lupus erythematosus    leukemia/lymphoma, t-cell    myelomeningocele    anencephaly

    3 Novoseek 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

    Publications
    for MTHFD1 gene

    (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)
    About This Section

    PubMed articles for MTHFD1 gene, integrated from 9 sources (see all 166):
    (articles sorted by number of sources associating them with MTHFD1)    		    Utopia: connect your pdf to the dynamic
    world of online information

    1. 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. (2002)
    2. 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. (1988)
    3. 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. (1998)
    4. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. (PubMed id 18767138)1, 2, 9 Christensen K.E.... Rozen R. (2009)
    5. Relationship between polymorphism of methylenetetrahydrofolate dehydrogenase and congenital heart defect. (PubMed id 15861780)1, 4, 9 Cheng J....Li Y. (2005)
    6. Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia. (PubMed id 14647408)1, 4, 9 Krajinovic M....Moghrabi A. (2004)
    7. 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, 9 Parle-McDermott A....Scott J.M. (2006)
    8. Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele. (PubMed id 15953655)1, 4, 9 Oterino A....Cid C. (2005)
    9. Polymorphisms in the one-carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study. (PubMed id 15122597)1, 4, 9 Chen J....Ma J. (2004)
    10. Prognostic significance of folate metabolism polymorphisms for lung cancer. (PubMed id 17533396)1, 7, 9 Matakidou A....Houlston R.S. (2007)

    External Searches for MTHFD1 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
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      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing MTHFD1 gene

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

    Other Databases showing MTHFD1 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing MTHFD1 gene

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

    Intellectual Property
    for MTHFD1 gene

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

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