DHFR


Summary: 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].

NameOMIM IDEnsembl IDHGNC IDPHARMGKB IDMap Location
dihydrofolate reductaseMIM:126060Ensembl:ENSG00000228716HGNC:HGNC:2861PA1435q14.1

Gene Categories:

DRUGGABLE GENOME

GO terms in DHFR


Term TypeEvidence TypeGO Term IDGO Des.
MFIDAGO:0000900translation repressor activity, mRNA regulatory element binding
MFIDAGO:0003729mRNA binding
MFIBAGO:0004146dihydrofolate reductase activity
MFIDAGO:0004146dihydrofolate reductase activity
MFISSGO:0004146dihydrofolate reductase activity
MFNASGO:0004146dihydrofolate reductase activity
MFIDAGO:0005542folic acid binding
MFIDAGO:0008144drug binding
MFTASGO:0033560folate reductase activity
MFIBAGO:0050661NADP binding
MFIDAGO:0051870methotrexate binding
MFIDAGO:0070402NADPH binding
MFIDAGO:1990825sequence-specific mRNA binding
BPTASGO:0000083regulation of transcription involved in G1/S transition of mitotic cell cycle
BPIMPGO:0006729tetrahydrobiopterin biosynthetic process
BPISSGO:0006729tetrahydrobiopterin biosynthetic process
BPIEAGO:0006730one-carbon metabolic process
BPIDAGO:0017148negative regulation of translation
BPISSGO:0031103axon regeneration
BPISSGO:0031427response to methotrexate
BPIBAGO:0046452dihydrofolate metabolic process
BPIDAGO:0046452dihydrofolate metabolic process
BPIDAGO:0046653tetrahydrofolate metabolic process
BPIBAGO:0046654tetrahydrofolate biosynthetic process
BPIDAGO:0046654tetrahydrofolate biosynthetic process
BPIEAGO:0046654tetrahydrofolate biosynthetic process
BPIBAGO:0046655folic acid metabolic process
BPISSGO:0046655folic acid metabolic process
BPTASGO:0046655folic acid metabolic process
BPISSGO:0051000positive regulation of nitric-oxide synthase activity
BPIDAGO:0055114oxidation-reduction process
BPISSGO:2000121regulation of removal of superoxide radicals
CCNDGO:0005575cellular_component
CCIBAGO:0005739mitochondrion
CCIDAGO:0005739mitochondrion
CCTASGO:0005829cytosol

Gene expression in normal tissue: DHFR

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in DHFR


DatabasePathway IDPathway Des.
wikipathwaysWP1601Fluoropyrimidine Activity
wikipathwaysWP176Folate Metabolism
wikipathwaysWP1858Mitotic G1-G1-S phases
wikipathwaysWP241One Carbon Metabolism
wikipathwaysWP2446Retinoblastoma (RB) in Cancer
wikipathwaysWP2525Trans-sulfuration and one carbon metabolism
wikipathwaysWP3996Ethanol effects on histone modifications
wikipathwaysWP404Nucleotide Metabolism
smpdbSMP00005Pterine Biosynthesis
smpdbSMP00053Folate Metabolism
smpdbSMP00432Methotrexate Action Pathway
smpdbSMP00486Dopa-responsive dystonia
smpdbSMP00487Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
smpdbSMP00488Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
smpdbSMP00489Hyperphenylalaninemia due to dhpr-deficiency
smpdbSMP00490Segawa syndrome
smpdbSMP00491Sepiapterin reductase deficiency
smpdbSMP00543Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
smpdbSMP00724Folate malabsorption, hereditary
pide2f_pathwayE2F transcription factor network
pharmgkbPA165291507Fluoropyrimidine Pathway, Pharmacodynamics
pharmgkbPA165291575Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
pharmgkbPA2039Methotrexate Pathway (Cancer Cell), Pharmacodynamics
pharmgkbPA2040Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics
biocartag1pathwaycell cycle: g1/s check point
reactomeR-HSA-1430728Metabolism
reactomeR-HSA-1430728Metabolism
reactomeR-HSA-1474151Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
reactomeR-HSA-1640170Cell Cycle
reactomeR-HSA-196757Metabolism of folate and pterines
reactomeR-HSA-196849Metabolism of water-soluble vitamins and cofactors
reactomeR-HSA-196854Metabolism of vitamins and cofactors
reactomeR-HSA-196854Metabolism of vitamins and cofactors
reactomeR-HSA-453279Mitotic G1-G1/S phases
reactomeR-HSA-539107Activation of E2F1 target genes at G1/S
reactomeR-HSA-69205G1/S-Specific Transcription
reactomeR-HSA-69206G1/S Transition
reactomeR-HSA-69278Cell Cycle, Mitotic
reactomeR-HSA-8978934Metabolism of cofactors
kegghsa00670One carbon pool by folate - Homo sapiens (human)
kegghsa00790Folate biosynthesis - Homo sapiens (human)
humancycPWY66-385dTMP de novo biosynthesis (mitochondrial)

Gene-Drug: Aster Plot


Drug IDDrug NameModel Num.
iGMDRD562Navitoclax3
iGMDRD780PP-3010
iGMDRD100Zebularine1
iGMDRD730Kahalalide F4
iGMDRD74Idarubicin4
iGMDRD23Gossypol3
iGMDRD598QS-114
iGMDRD268Cerulenin4
iGMDRD451Serdemetan5
iGMDRD690PRIMA-1MET4
iGMDRD369TGX-1153
iGMDRD255SB2250026
iGMDRD226ML0063
iGMDRD8012,4-dideoxy-DC-45-A25
iGMDRD187BRD98763
iGMDRD316N9-Isopropyl-olomoucine5
iGMDRD193Fqi13
iGMDRD61Kinetin riboside3
iGMDRD163all trans Retinoic Acid5
iGMDRD793BEC (hydrochloride)4
iGMDRD446LY 21832404
iGMDRD375GW-4058334
iGMDRD297Austocystin D3
iGMDRD466Chaetocin1
iGMDRD280CYTOCHALASIN B5
iGMDRD579PF7505
iGMDRD425ERASTIN5
iGMDRD126Tipifarnib10
iGMDRD781Sirolimus3
iGMDRD329Merck605
iGMDRD871BRD63683
iGMDRD367Ro 28-16754
iGMDRD872BRD71373
iGMDRD147Prima-15
iGMDRD137Indisulam2
iGMDRD415LE-1354
iGMDRD213SMR0000686505
iGMDRD6AM-5805
iGMDRD221Tamoxifen5
iGMDRD192CIL564
iGMDRD536PLX-47201
iGMDRD248BRD43543
iGMDRD307Manumycin A3
iGMDRD79Gemcitabine3
iGMDRD532Olaparib5
iGMDRD150RITA3
iGMDRD345Compound 10b [PMID: 11504634]2

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in DHFR

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