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DHFR Gene

protein-coding   GIFtS: 70
GCID: GC05M079922

Dihydrofolate Reductase

  See 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
Dihydrofolate Reductase1 2
EC 1.5.1.33 8
DHFRP12
DYR2

External Ids:    HGNC: 28611   Entrez Gene: 17192   Ensembl: ENSG000002287167   OMIM: 1260605   UniProtKB: P003743   

Export aliases for DHFR gene to outside databases

Previous GC identifers: GC05M078744 GC05M080160 GC05M079960 GC05M080006 GC05M079957


(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 DHFR Gene:
Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de
novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase
gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like
genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to
megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene.
(provided by RefSeq, Mar 2014)

GeneCards Summary for DHFR Gene:
DHFR (dihydrofolate reductase) is a protein-coding gene. Diseases associated with DHFR include megaloblastic anemia due to dihydrofolate reductase deficiency, and isosporiasis. An important paralog of this gene is DHFRL1.

UniProtKB/Swiss-Prot: DYR_HUMAN, P00374
Function: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis
pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor
synthesis. Binds its own mRNA and that of DHFRL1

summary for DHFR Gene:
Dihydrofolate reductase (DHFR) is a member of the reductase family of enzymes that is ubiquitously expressed
in all organisms. It catalyzes tetrahydrofolate regeneration by reduction of dihydrofolate, using NADPH as a
cofactor. Tetrahydrofolate is essential for de novo purine and thymidylate synthesis, hence DHFR has a
critical role in cell growth and proliferation. DHFR is the target for many anticancer and antibiotic
therapies including methotrexate and trimethoprim. Basal and regulated DHFR gene expression is controlled by
Sp1 and E2F family transcription factors respectively and levels of this enzyme peak at the G1/S cell cycle
boundary. Autoregulation, through DHFR-RNA interactions, has also been reported. The human gene encoding
this enzyme is localized to 5q11.2-13.2.

Gene Wiki entry for DHFR (Dihydrofolate reductase) 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:
NC_000005.10  NT_034772.7  NC_018916.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the DHFR gene promoter:
         USF1   Sp1   p53   USF-1:USF-2   C/EBPalpha   Pax-3   POU2F1   POU2F1a   USF-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): DHFR promoter sequence
   Search Chromatin IP Primers for DHFR

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


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

Entrez Gene cytogenetic band: 5q11.2-q13.2   Ensembl cytogenetic band:  5q14.1   HGNC cytogenetic band: 5q11.2-q13.2

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

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05M079922:  view genomic region     (about GC identifiers)

Start:
79,922,045 bp from pter      End:
79,950,802 bp from pter
Size:
28,758 bases      Orientation:
minus 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: DYR_HUMAN, P00374 (See protein sequence)
Recommended Name: Dihydrofolate reductase  
Size: 187 amino acids; 21453 Da
Subunit: Homodimer
Selected PDB 3D structures from and Proteopedia for DHFR (see all 63):
1BOZ (3D)        1DHF (3D)        1DLR (3D)        1DLS (3D)        1DRF (3D)        1HFP (3D)    
Secondary accessions: Q14130 Q6IRW8

Explore the universe of human proteins at neXtProt for DHFR: NX_P00374

Explore proteomics data for DHFR at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys19, Lys56, Lys81, Lys133, Lys158, Lys174, Lys179, Lys185
  • Modification sites at PhosphoSitePlus
  • 3 DME Specific Peptides for DHFR (P00374)
     QNMGIGK  KQNLVIMG  VLSRELKEPPQGAHFL 


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

    REFSEQ proteins (3 alternative transcripts): 
    NP_000782.1  NP_001277283.1  NP_001277286.1  

    ENSEMBL proteins: 
     ENSP00000396308   ENSP00000426474   ENSP00000422732   ENSP00000421334  
    Reactome Protein details: P00374

    DHFR Human Recombinant Protein Products:

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    Novus Biologicals DHFR Proteins
    Novus Biologicals DHFR Lysates
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    Browse Sino Biological Cell Lysates
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    DHFR Antibody Products:

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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for DHFR
    Cloud-Clone Corp. CLIAs for DHFR


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    4 InterPro protein domains:
     IPR024072 DHFR-like_dom
     IPR012259 DHFR
     IPR001796 DHFR_dom
     IPR017925 DHFR_CS

    Graphical View of Domain Structure for InterPro Entry P00374

    ProtoNet protein and cluster: P00374

    1 Blocks protein domain: IPB001796 Dihydrofolate reductase

    UniProtKB/Swiss-Prot: DYR_HUMAN, P00374
    Similarity: Belongs to the dihydrofolate reductase family
    Similarity: Contains 1 DHFR (dihydrofolate reductase) domain


    DHFR for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, 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, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DYR_HUMAN, P00374
    Function: Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis
    pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor
    synthesis. Binds its own mRNA and that of DHFRL1
    Catalytic activity: 5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
    Biophysicochemical properties: Kinetic parameters: KM=2.7 uM for dihydrofolate; KM=4.0 uM for NADPH;

         Genatlas biochemistry entry for DHFR:
    dihydrofolate reductase,putative up-regulated c-Myc target gene,DNA metabolism

         Enzyme Number (IUBMB): EC 1.5.1.31 2

         Gene Ontology (GO): 4 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003729mRNA binding ----
    GO:0004146dihydrofolate reductase activity ----
    GO:0008144drug binding ----
    GO:0050661NADP binding ----
         
    DHFR for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for DHFR:
     Decreased circadian period len 

         1 MGI phenotypic allele for Dhfr (no phenotypes)

    DHFR for phenotypes           About GeneDecksing

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for DHFR
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    miRNA
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    miRTarBase miRNAs that target DHFR:
    hsa-mir-15b-5p (MIRT046435), hsa-mir-935 (MIRT036640), hsa-mir-93-3p (MIRT038796), hsa-mir-24-3p (MIRT002018), hsa-mir-99b-5p (MIRT044182), hsa-mir-503-5p (MIRT041132)

    Block miRNA regulation of human, mouse, rat DHFR using miScript Target Protectors
    Search for qRT-PCR Assays for microRNAs that regulate DHFR
    SwitchGear 3'UTR luciferase reporter plasmidDHFR 3' UTR sequence
    Inhib. RNA
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    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector: DHFR (NM_000791)
    Sino Biological Human cDNA Clone for DHFR
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DHFR

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DHFR


    (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 COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus4
    mitochondrion3
    plasma membrane2
    chloroplast1
    endoplasmic reticulum1
    extracellular1
    lysosome1
    peroxisome1
    vacuole1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005575cellular_component ----
    GO:0005654nucleoplasm ----
    GO:0005829cytosol ----

    DHFR for ontologies           About GeneDecksing


    (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 DHFR About   (see all 12)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1One carbon pool by folate
    One carbon pool by folate0.53
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics0.35
    One Carbon Metabolism0.53
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics0.34
    Trans-sulfuration and one carbon metabolism0.43
    Antimetabolite Pathway - Folate Cycle, Pharmacodynamics0.00
    2Pyrimidine metabolism
    Fluoropyrimidine Activity0.69
    Fluoropyrimidine Pathway, Pharmacodynamics0.00
    3Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    4Defective 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
    5E2F mediated regulation of DNA replication
    G1/S Transition0.81
    E2F mediated regulation of DNA replication0.30
    Mitotic G1-G1/S phases0.81
    G1/S-Specific Transcription0.00

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    Selected BioSystems Pathways for DHFR (see all 6)
        One Carbon Metabolism
    Fluoropyrimidine Activity
    Nucleotide Metabolism
    RB in Cancer
    E2F transcription factor network


    4 Reactome Pathways for DHFR
        Metabolism of folate and pterines
    Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
    E2F mediated regulation of DNA replication
    G1/S-Specific Transcription

    4 PharmGKB Pathways for DHFR
        Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
    Fluoropyrimidine Pathway, Pharmacodynamics
    Methotrexate Pathway (Cancer Cell), Pharmacodynamics
    Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

    3 Kegg Pathways  (Kegg details for DHFR):
        One carbon pool by folate
    Folate biosynthesis
    Metabolic pathways

    UniProtKB/Swiss-Prot: DYR_HUMAN, P00374
    Pathway: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate:
    step 1/1


    DHFR for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including DHFR: 

              Cancer Drug Resistance in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for DHFR

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

    Selected Interacting proteins for DHFR (P003743 ENSP000003963084) via UniProtKB, MINT, STRING, and/or I2D (see all 57)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    FKBP1AP629423, ENSP000003711384I2D: score=3 STRING: ENSP00000371138
    HSPD1P108093, ENSP000003400194I2D: score=3 STRING: ENSP00000340019
    ASGR1P073063, ENSP000002692994I2D: score=2 STRING: ENSP00000269299
    MDM2Q009873, ENSP000004172814I2D: score=2 STRING: ENSP00000417281
    TOMM20Q153883, ENSP000003555664I2D: score=2 STRING: ENSP00000355566
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000082G1/S transition of mitotic cell cycle ----
    GO:0000083regulation of transcription involved in G1/S transition of mitotic cell cycle ----
    GO:0000278mitotic cell cycle ----
    GO:0006545glycine biosynthetic process ----
    GO:0006730one-carbon metabolic process ----

    DHFR for ontologies           About GeneDecksing



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

    Compounds for DHFR available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CI 898 trihydrochlorideDihydrofolate reductase inhibitor[82952-64-5]

    7 HMDB Compounds for DHFR    About this table
    CompoundSynonyms CAS #PubMed Ids
    Dihydrobiopterin(S-(R*,S*))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone (see all 15)6779-87-93189762
    Dihydrofolic acid7,8-Dihydro-L-folic acid (see all 13)4033-27-6--
    Dimethyl sulfoxide(methylsulfinyl)methane;Dimethyl sulfoxide (see all 5)67-68-5--
    Folic acidAcifolic (see all 37)59-30-3--
    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--
    Tetrahydrofolic acid(6S)-Tetrahydrofolate (see all 10)135-16-0--

    Selected DrugBank Compounds for DHFR (see all 29)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    PemetrexedLY231514 (see all 2)150399-23-8targetinhibitor15795320 11742712 14596699 11763166 12571811 11752352 11252887 11531245 12023793 11524555 11848474 11841783
    MethotrexateAmethopterin (see all 12)59-05-2targetinhibitor16971132 17333344 16647263 11752352 17130456 16936229
    enzymesubstrate16971132 17333344 16647263 11752352 17130456 16936229 17586865
    TrimetrexateTMQ (see all 4)52128-35-5targetinhibitor10386066 12649191 11752096 10091649 11752352 11448221 12416030
    Proguanil-- 500-92-5targetinhibitor10068594 12667224 11752352 11295178 10998224 11740746
    Trimethoprim-- 738-70-5targetinhibitor15561838 11752352 14632594 15115391 15504856 14629008
    PyrimethamineCD (see all 12)58-14-0targetinhibitor12951104 11752352 9108546 9380737
    2,4-Diamino-5-Methyl-6-[(3,4,5-Trimethoxy-N-Methylanilino)Methyl]Pyrido[2,3-D]Pyrimidine-- --target--17139284 17016423 10592235
    2,4-Diamino-6-[N-(3',4',5'-Trimethoxybenzyl)-N-Methylamino]Pyrido[2,3-D]Pyrimidine-- --target--17139284 17016423 10592235
    6-(2,5-Dimethoxy-Benzyl)-5-Methyl-Pyrido[2,3-D]Pyrimidine-2,4-Diamine-- --target--17139284 17016423 10592235
    6-(Octahydro-1h-Indol-1-Ylmethyl)Decahydroquinazoline-2,4-Diamine-- --target--17139284 17016423 10592235

    Selected Novoseek inferred chemical compound relationships for DHFR gene (see all 127)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    dihydrofolate 99.4 2737 1825652 (8), 7812005 (8), 19570950 (7), 9174938 (5) (see all 99)
    dihydropteroate 93.5 177 15047993 (3), 19707564 (3), 8780462 (2), 10466980 (2) (see all 90)
    trimetrexate 93.3 67 1825652 (4), 8630426 (2), 8043612 (2), 10091649 (2) (see all 41)
    thymidylate 92.2 334 1825652 (4), 8486425 (3), 18067453 (3), 1435754 (3) (see all 99)
    glycinamide ribonucleotide 91.6 69 15655941 (2), 9420020 (1), 11848474 (1), 12209673 (1) (see all 53)
    methotrexate 90.6 914 15817466 (7), 19570950 (6), 7476904 (5), 8852336 (5) (see all 99)
    piritrexim 90.4 55 7799402 (3), 8230096 (3), 15571870 (2), 17346178 (2) (see all 20)
    pyrimethamine 90.3 181 12805261 (5), 10950805 (4), 10466054 (3), 10813484 (3) (see all 93)
    pt523 89.2 30 10739874 (4), 9109647 (3), 12732354 (2), 10101216 (2) (see all 15)
    sulfadoxine/pyrimethamine 88.4 147 15228255 (6), 12805261 (5), 10466980 (4), 16023986 (4) (see all 44)

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



    DHFR for compounds           About GeneDecksing



    (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, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for DHFR gene (3 alternative transcripts): 
    NM_000791.3  NM_001290354.1  NM_001290357.1  

    Unigene Clusters for DHFR:

    Dihydrofolate reductase
    Hs.592364  [show with all ESTs], Hs.648635  [show with all ESTs]
    Unigene Representative Sequences: CD014129, NM_000791
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000439211(uc003kgy.1 uc011ctl.2 uc011ctm.2 uc010jap.2)
    ENST00000505337 ENST00000511032 ENST00000504396 ENST00000513048 ENST00000508282
    ENST00000513314
    miRNA
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    Block miRNA regulation of human, mouse, rat DHFR using miScript Target Protectors
    Search for qRT-PCR Assays for microRNAs that regulate DHFR
    SwitchGear 3'UTR luciferase reporter plasmidDHFR 3' UTR sequence
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for DHFR
    Predesigned siRNA for gene silencing in human, mouse, rat DHFR
    Clone
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    OriGene clones in human, mouse for DHFR (see all 6)
    OriGene ORF clones in mouse, rat for DHFR
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: DHFR (NM_000791)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for DHFR
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat DHFR
    Primer
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      QuantiFast Probe-based Assays in human, mouse, rat DHFR

    Additional mRNA sequence: 

    AK293146.1 AK297302.1 AK308492.1 AK312642.1 BC000192.1 BC003584.1 BC009634.1 BC070280.1 
    BC071996.1 J00140.1 

    18 DOTS entries:

    DT.447611  DT.92455271  DT.95072429  DT.100788057  DT.100788054  DT.120851016  DT.86993768  DT.91665623 
    DT.95072431  DT.100788059  DT.120851003  DT.120851009  DT.121086751  DT.121086765  DT.121086769  DT.40307308 
    DT.110960  DT.92455274 

    Selected AceView cDNA sequences (see all 293):

    AI919237 BE858788 AU130196 BQ644196 BU632674 BG328723 CF136591 AA129465 
    BE766051 BI759776 AI262751 BF940121 V00507 AI419234 AA974401 BQ432463 
    AV711675 AI381187 CK820514 AI626046 CA424783 T29009 AA447680 AA749344 

    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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    DHFR expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAGGTAACTA
    DHFR Expression
    About this image


    DHFR expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
     
     Thymus (Hematopoietic System)
             Thymus
    DHFR Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    DHFR Protein Expression

    SOURCE GeneReport for Unigene clusters: Hs.592364 Hs.648635

    UniProtKB/Swiss-Prot: DYR_HUMAN, P00374
    Tissue specificity: Widely expressed in fetal and adult tissues, including throughout the fetal and adult brains
    and whole blood. Expression is higher in the adult brain than in the fetal brain

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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 animals and fungi.

    Orthologs for DHFR gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Dhfr1 , 5 dihydrofolate reductase1, 5 88.41(n)1
    89.84(a)1
      13 (47.64 cM)5
    133611  NM_010049.31  NP_034179.11 
     923547835 
    chicken
    (Gallus gallus)
    Aves DHFR1 dihydrofolate reductase 78.14(n)
    75.27(a)
      427317  NM_001006584.2  NP_001006584.2 
    lizard
    (Anolis carolinensis)
    Reptilia --
    Uncharacterized protein
    75(a)
    1 → many
    2(17183439-17203894)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.76162 Xenopus laevis transcribed sequence with weak similarity more 72.77(n)    AW646094.1 
    zebrafish
    (Danio rerio)
    Actinopterygii dhfr2 dihydrofolate reductase 73.64(n)   81882  AY026507.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Dhfr1 , 3 'de novo' IMP biosynthesis
    dihydrofolate reductase3
    Dihydrofolate reductase1
    46(a)3
    53.22(n)1
    48.3(a)1
      89D23
    420031  NM_169721.21  NP_732147.11 
    worm
    (Caenorhabditis elegans)
    Secernentea dhfr-11 dhfr-1 47.43(n)
    36.57(a)
      172681  NM_059963.3  NP_492364.1 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes DFR16
    Dihydrofolate reductase, part of the dTTP biosynth...
    29(a)
    1 → many
    XV(780906-781541) YOR236W


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for DHFR gene
    DHFRL12  
    2 SIMAP similar genes for DHFR using alignment to 3 protein entries:     DYR_HUMAN (see all proteins):
    DYR    DHFRL1

    DHFR for paralogs           About GeneDecksing


    Selected Pseudogenes.org Pseudogenes for DHFR (see all 7)
    PGOHUM00000250460 PGOHUM00000243142 PGOHUM00000243211 PGOHUM00000243224 PGOHUM00000245352


    (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 DHFR (see all 535)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0658194
    Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)4--see VAR_0658192 D V mis40--------
    VAR_0658184
    Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)4--see VAR_0658182 L F mis40--------
    rs3758538101,2
    C--79922250(+) TTATT-/TTTTTTT 2 -- ut310--------
    rs792018491,2
    C--79926196(+) TTTTTC/G/TTTTGA 1 -- int11NA 2
    rs673313141,2
    C--79926567(+) TTGGT-/AAAAAA 1 -- int11Minor allele frequency- A:0.00NA 2
    rs1456083121,2
    C--79930523(+) AAAAT-/ACAC/ACAC
    ACACACACACAC
    ACACA
    1 -- int10--------
    rs341414871,2
    C--79930524(+) AAATA-/ACAC/ACAC
    ACACACACACAC
    CACAC
    1 -- int10--------
    rs598325491,2
    C--79930546(+) ACACA-/CACA/CACA
    CACACACACACA
    ACAAA
    1 -- int11NA 2
    rs16776991,2
    C,F--79931811(-) AAAAAC/ACTCTC 1 -- int14Minor allele frequency- A:0.50WA NA 8
    rs1415083151,2
    C--79933654(+) GAAAG-/AAA   
      G
    /GAAA
    TAGAA
    1 -- int10--------

    HapMap Linkage Disequilibrium report for DHFR (79922045 - 79950802 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for DHFR:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv4895CNV Insertion18451855
    esv23209CNV Loss19812545
    nsv483112CNV Loss15286789
    nsv10709CNV Loss18304495
    esv23281CNV Gain+Loss19812545

    Human Gene Mutation Database (HGMD): DHFR
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing DHFR
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    (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.)
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    OMIM gene information: 126060   
    OMIM disorders: 613839  
    UniProtKB/Swiss-Prot: DYR_HUMAN, P00374
  • Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]: An inborn error of
    metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and
    cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from
    severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning
    difficulties, to lack of symptoms. Note=The disease is caused by mutations affecting the gene represented in this
    entry

  • Selected diseases for DHFR (see all 89):    
    About MalaCards
    megaloblastic anemia due to dihydrofolate reductase deficiency    isosporiasis    candida glabrata    cryptosporidiosis
    toxoplasmosis    plasmodium falciparum malaria    megaloblastic anemia    stenotrophomonas maltophilia
    cerebral folate deficiency    homocysteine plasma level    pneumocystosis    pediatric osteosarcoma
    pancytopenia    tetrahydrobiopterin deficiency    benign mesothelioma    chagas disease
    malaria    spina bifida    osteosarcoma    childhood absence epilepsy

    5 diseases from the University of Copenhagen DISEASES database for DHFR:
    Malaria     Pneumocystosis     Leukemia     Megaloblastic anemia
    Acquired immunodeficiency syndrome

    DHFR for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for DHFR gene (see all 81)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    malaria falciparum 75.9 16 15374529 (2), 19055622 (2), 10466980 (1), 16124424 (1) (see all 11)
    malaria 73 62 9380737 (2), 15718161 (2), 10432069 (2), 16023986 (1) (see all 42)
    leukemia l1210 54.8 6 1825999 (2), 1313737 (1), 8246224 (1)
    leukemia 53.6 37 8449831 (2), 11380466 (2), 17148505 (2), 8568827 (1) (see all 25)
    osteosarcoma 47.5 17 14679136 (5), 19159907 (3), 18385200 (2), 12813132 (2) (see all 5)
    folate deficiency 45.1 3 7687143 (1), 19850982 (1), 18804693 (1)
    solid tumor 45.1 4 9300877 (1), 15359285 (1), 11173547 (1), 16372519 (1)
    mesothelioma 44.4 1 15359285 (1)
    retinoblastoma 39.8 8 9591776 (2), 15590111 (1), 11380466 (1), 14679136 (1) (see all 5)
    tumors 39.8 96 2016722 (2), 8259106 (2), 7553969 (2), 1727369 (2) (see all 49)

    Genatlas disease: DHFR
    anemia,megaloblastic

    Genetic Association Database (GAD): DHFR
    Human Genome Epidemiology (HuGE) Navigator: DHFR (68 documents)

    Export disorders for DHFR 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 DHFR gene, integrated from 10 sources (see all 1110):
    (articles sorted by number of sources associating them with DHFR)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A functional 19-base pair deletion polymorphism of dihydrofolate reductase (DHFR) and risk of breast cancer in multivitamin users. (PubMed id 17413111)1, 4, 9 Xu X....Chen J. (Am. J. Clin. Nutr. 2007)
    2. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate. (PubMed id 19022952)1, 4, 9 Kalmbach R.D....Selhub J. (J. Nutr. 2008)
    3. Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution. (PubMed id 1731871)1, 2, 9 Stockman B.J....Freisheim J.H. (Biochemistry 1992)
    4. Genetic association study of putative functional single nucleotide polymorphisms of genes in folate metabolism and spina bifida. (PubMed id 19683694)1, 4, 9 Martinez C.A....Au K.S. (Am. J. Obstet. Gynecol. 2009)
    5. The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis. (PubMed id 18682947)1, 4, 9 Eroglu A....Akar N. (Ann. Hematol. 2009)
    6. Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery. (PubMed id 15755837)1, 4, 9 Johnson W.G....Chen X. (Am. J. Clin. Nutr. 2005)
    7. Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523. (PubMed id 9374868)1, 2, 9 Cody V....Gangjee A. (Biochemistry 1997)
    8. DNA variants in region for noncoding interfering transcript of dihydrofolate reductase gene and outcome in childhood acute lymphoblastic leukemia. (PubMed id 19861437)1, 4, 9 Al-Shakfa F....Krajinovic M. (Clin. Cancer Res. 2009)
    9. Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes. (PubMed id 19196009)1, 2, 9 Cody V.... Rosowsky A. (Biochemistry 2009)
    10. Dihydrofolate reductase (DHRF) 19-bp intron-1 deletion and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in breast cancer. (PubMed id 18498051)1, 4, 9 Cam R....Akar N. (Breast Cancer Res. Treat. 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: 1719 HGNC: 2861 AceView: DHFR Ensembl:ENSG00000228716 euGenes: HUgn1719
    ECgene: DHFR Kegg: 1719 H-InvDB: DHFR

    (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 DHFR Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for DHFR Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Dihydrofolate_reductase

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

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



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