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Aliases for DHFR Gene

Aliases for DHFR Gene

  • Dihydrofolate Reductase 2 3
  • EC 4 64
  • DHFRP1 3
  • DYR 3

External Ids for DHFR Gene

Summaries for DHFR Gene

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 pneumocystosis. Among its related pathways are Disease and Cell Cycle, Mitotic. An important paralog of this gene is DHFRL1.

UniProtKB/Swiss-Prot for DHFR Gene

  • 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.

Tocris 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 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DHFR Gene

Genomics for DHFR Gene

Genomic Location for DHFR Gene

80,626,226 bp from pter
80,654,983 bp from pter
28,758 bases
Minus strand

Genomic View for DHFR Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for DHFR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DHFR Gene

Regulatory Elements for DHFR Gene

Proteins for DHFR Gene

  • Protein details for DHFR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Dihydrofolate reductase
    Protein Accession:
    Secondary Accessions:
    • B4DDD2
    • Q14130
    • Q6IRW8

    Protein attributes for DHFR Gene

    187 amino acids
    Molecular mass:
    21453 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for DHFR Gene

    Alternative splice isoforms for DHFR Gene


neXtProt entry for DHFR Gene

Proteomics data for DHFR Gene at MOPED

Selected DME Specific Peptides for DHFR Gene

Post-translational modifications for DHFR Gene

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys19, Lys56, Lys81, Lys133, Lys158, Lys174, Lys179, and Lys185

Other Protein References for DHFR Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for DHFR Gene

Protein Domains for DHFR Gene


  • Contains 1 DHFR (dihydrofolate reductase) domain.:
    • P00374
  • Belongs to the dihydrofolate reductase family.:
    • P00374
genes like me logo Genes that share domains with DHFR: view

No data available for Gene Families for DHFR Gene

Function for DHFR Gene

Molecular function for DHFR Gene

GENATLAS Biochemistry: dihydrofolate reductase,putative up-regulated c-Myc target gene,DNA metabolism
UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=2.7 uM for dihydrofolate {ECO:0000269 PubMed:15039552, ECO:0000269 PubMed:19196009, ECO:0000269 PubMed:21876184}; KM=4.0 uM for NADPH {ECO:0000269 PubMed:15039552, ECO:0000269 PubMed:19196009, ECO:0000269 PubMed:21876184};
UniProtKB/Swiss-Prot CatalyticActivity: 5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for DHFR Gene

Gene Ontology (GO) - Molecular Function for DHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003729 mRNA binding IDA 21876184
GO:0004146 dihydrofolate reductase activity NAS 6687716
GO:0008144 drug binding IDA 12096917
GO:0050661 NADP binding IEA --
genes like me logo Genes that share ontologies with DHFR: view

Phenotypes for DHFR Gene

GenomeRNAi human phenotypes for DHFR:
genes like me logo Genes that share phenotypes with DHFR: view

No data available for Animal Models , Transcription Factor Targeting and HOMER Transcription for DHFR Gene

Localization for DHFR Gene

Subcellular locations from

Jensen Localization Image for DHFR Gene COMPARTMENTS Subcellular localization image for DHFR gene
Compartment Confidence
cytosol 4
nucleus 4
mitochondrion 3
plasma membrane 2
chloroplast 1
endoplasmic reticulum 1
extracellular 1
lysosome 1
peroxisome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for DHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005575 cellular_component ND --
GO:0005654 nucleoplasm TAS --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with DHFR: view

Pathways for DHFR Gene

SuperPathways for DHFR Gene

Superpath Contained pathways
1 Defective BTD causes biotidinase deficiency
2 One carbon pool by folate
3 Metabolism of nitric oxide
4 Cell Cycle, Mitotic
5 Metabolism
genes like me logo Genes that share pathways with DHFR: view

UniProtKB/Swiss-Prot P00374-DYR_HUMAN

  • Pathway: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1

Gene Ontology (GO) - Biological Process for DHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000082 G1/S transition of mitotic cell cycle TAS --
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle TAS --
GO:0000278 mitotic cell cycle TAS --
GO:0006545 glycine biosynthetic process IEA --
GO:0006730 one-carbon metabolic process IEA --
genes like me logo Genes that share ontologies with DHFR: view

Compounds for DHFR Gene

(1) Tocris Compounds for DHFR Gene

Compound Action Cas Number
CI 898 trihydrochloride Dihydrofolate reductase inhibitor [82952-64-5]

(7) HMDB Compounds for DHFR Gene

Compound Synonyms Cas Number PubMed IDs
  • (S-(R*,S*))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone
Dihydrofolic acid
  • 7,8-Dihydro-L-folic acid
Dimethyl sulfoxide
  • (methylsulfinyl)methane
Folic acid
  • Acifolic
  • Adenine-nicotinamide dinucleotide phosphate

(127) Novoseek inferred chemical compound relationships for DHFR Gene

Compound -log(P) Hits PubMed IDs
dihydrofolate 99.4 280
dihydropteroate 93.5 114
trimetrexate 93.3 49
thymidylate 92.2 134
glycinamide ribonucleotide 91.6 54

(1) PharmGKB related drug/compound annotations for DHFR Gene

Drug/compound Annotation
methotrexate CA
genes like me logo Genes that share compounds with DHFR: view

Transcripts for DHFR Gene

Unigene Clusters for DHFR Gene

Dihydrofolate reductase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for DHFR Gene

No ASD Table

Relevant External Links for DHFR Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for DHFR Gene

mRNA expression in normal human tissues for DHFR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for DHFR Gene

SOURCE GeneReport for Unigene cluster for DHFR Gene Hs.592364

mRNA Expression by UniProt/SwissProt for DHFR Gene

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.
genes like me logo Genes that share expressions with DHFR: view

Orthologs for DHFR Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for DHFR Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia DHFR 36
  • 99.82 (n)
  • 99.47 (a)
  • 99 (a)
(Bos Taurus)
Mammalia DHFR 36
  • 89.84 (n)
  • 86.63 (a)
  • 87 (a)
(Canis familiaris)
Mammalia -- 37
  • 91 (a)
-- 37
  • 94 (a)
  • 91.85 (n)
  • 90.76 (a)
(Mus musculus)
Mammalia Dhfr 36
  • 88.41 (n)
  • 89.84 (a)
Dhfr 16
Dhfr 37
  • 90 (a)
(Monodelphis domestica)
Mammalia -- 37
  • 81 (a)
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 62 (a)
(Rattus norvegicus)
Mammalia Dhfr 36
  • 89.3 (n)
  • 89.84 (a)
(Gallus gallus)
Aves DHFR 36
  • 78.14 (n)
  • 75.27 (a)
  • 74 (a)
(Anolis carolinensis)
Reptilia -- 37
  • 75 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.7616 36
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100486206 36
  • 68.69 (n)
  • 65.19 (a)
Str.3499 36
(Danio rerio)
Actinopterygii dhfr 36
  • 66.3 (n)
  • 62.22 (a)
dhfr 37
  • 59 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010278 36
  • 51.48 (n)
  • 42.78 (a)
fruit fly
(Drosophila melanogaster)
Insecta Dhfr 36
  • 53.22 (n)
  • 48.3 (a)
Dhfr 37
  • 47 (a)
Dhfr 38
  • 46 (a)
(Caenorhabditis elegans)
Secernentea dhfr-1 36
  • 47.43 (n)
  • 36.57 (a)
dhfr-1 37
  • 33 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes DFR1 37
  • 29 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes dfr1 36
  • 49.27 (n)
  • 40.66 (a)
Species with no ortholog for DHFR:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for DHFR Gene

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

Paralogs for DHFR Gene

Paralogs for DHFR Gene

Selected SIMAP similar genes for DHFR Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with DHFR: view

Variants for DHFR Gene

Sequence variations from dbSNP and Humsavar for DHFR Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type MAF
rs7387 -- 80,628,972(+) AAAAC(A/T)AGTTG utr-variant-3-prime, nc-transcript-variant
rs14435 -- 80,626,963(+) ctaag(A/G)tggcc utr-variant-3-prime, nc-transcript-variant
rs165957 -- 80,630,554(+) agacg(G/T)ggttt intron-variant
rs245099 -- 80,639,273(-) CATCA(A/G)CTATT intron-variant
rs245100 -- 80,637,274(-) CAACA(C/T)GTTGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for DHFR Gene

Variant ID Type Subtype PubMed ID
nsv483112 CNV Loss 15286789
nsv4895 CNV Insertion 18451855
esv23209 CNV Loss 19812545
nsv10709 CNV Loss 18304495
esv23281 CNV Gain+Loss 19812545

Relevant External Links for DHFR Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

Disorders for DHFR Gene

(1) OMIM Diseases for DHFR Gene (126060)


  • 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. {ECO:0000269 PubMed:21310276, ECO:0000269 PubMed:21310277}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(81) Novoseek inferred disease relationships for DHFR Gene

Disease -log(P) Hits PubMed IDs
malaria falciparum 75.9 13
malaria 73 45
leukemia l1210 54.8 4
leukemia 53.6 28
osteosarcoma 47.5 13

Genatlas disease for DHFR Gene


Relevant External Links for DHFR

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with DHFR: view

Publications for DHFR Gene

  1. Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. (PMID: 2248959) Davies J.F. … Kraut J. (Biochemistry 1990) 3 4 23
  2. Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution. (PMID: 1731871) Stockman B.J. … Freisheim J.H. (Biochemistry 1992) 3 4 23
  3. 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. (PMID: 9374868) Cody V. … Gangjee A. (Biochemistry 1997) 3 4 23
  4. A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression. (PMID: 11448909) Goto Y. … Saikawa Y. (Clin. Cancer Res. 2001) 3 23 49
  5. Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery. (PMID: 15755837) Johnson W.G. … Chen X. (Am. J. Clin. Nutr. 2005) 3 23 49

Products for DHFR Gene

Sources for DHFR Gene

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