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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| dihydrofolate reductase | MIM:126060 | Ensembl:ENSG00000228716 | HGNC:HGNC:2861 | PA143 | 5q14.1 |
Gene Categories:
DRUGGABLE GENOMEGO terms in DHFR
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IDA | GO:0000900 | translation repressor activity, mRNA regulatory element binding |
| MF | IDA | GO:0003729 | mRNA binding |
| MF | IBA | GO:0004146 | dihydrofolate reductase activity |
| MF | IDA | GO:0004146 | dihydrofolate reductase activity |
| MF | ISS | GO:0004146 | dihydrofolate reductase activity |
| MF | NAS | GO:0004146 | dihydrofolate reductase activity |
| MF | IDA | GO:0005542 | folic acid binding |
| MF | IDA | GO:0008144 | drug binding |
| MF | TAS | GO:0033560 | folate reductase activity |
| MF | IBA | GO:0050661 | NADP binding |
| MF | IDA | GO:0051870 | methotrexate binding |
| MF | IDA | GO:0070402 | NADPH binding |
| MF | IDA | GO:1990825 | sequence-specific mRNA binding |
| BP | TAS | GO:0000083 | regulation of transcription involved in G1/S transition of mitotic cell cycle |
| BP | IMP | GO:0006729 | tetrahydrobiopterin biosynthetic process |
| BP | ISS | GO:0006729 | tetrahydrobiopterin biosynthetic process |
| BP | IEA | GO:0006730 | one-carbon metabolic process |
| BP | IDA | GO:0017148 | negative regulation of translation |
| BP | ISS | GO:0031103 | axon regeneration |
| BP | ISS | GO:0031427 | response to methotrexate |
| BP | IBA | GO:0046452 | dihydrofolate metabolic process |
| BP | IDA | GO:0046452 | dihydrofolate metabolic process |
| BP | IDA | GO:0046653 | tetrahydrofolate metabolic process |
| BP | IBA | GO:0046654 | tetrahydrofolate biosynthetic process |
| BP | IDA | GO:0046654 | tetrahydrofolate biosynthetic process |
| BP | IEA | GO:0046654 | tetrahydrofolate biosynthetic process |
| BP | IBA | GO:0046655 | folic acid metabolic process |
| BP | ISS | GO:0046655 | folic acid metabolic process |
| BP | TAS | GO:0046655 | folic acid metabolic process |
| BP | ISS | GO:0051000 | positive regulation of nitric-oxide synthase activity |
| BP | IDA | GO:0055114 | oxidation-reduction process |
| BP | ISS | GO:2000121 | regulation of removal of superoxide radicals |
| CC | ND | GO:0005575 | cellular_component |
| CC | IBA | GO:0005739 | mitochondrion |
| CC | IDA | GO:0005739 | mitochondrion |
| CC | TAS | GO:0005829 | cytosol |
Gene expression in normal tissue: DHFR
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in DHFR
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| wikipathways | WP1601 | Fluoropyrimidine Activity |
| wikipathways | WP176 | Folate Metabolism |
| wikipathways | WP1858 | Mitotic G1-G1-S phases |
| wikipathways | WP241 | One Carbon Metabolism |
| wikipathways | WP2446 | Retinoblastoma (RB) in Cancer |
| wikipathways | WP2525 | Trans-sulfuration and one carbon metabolism |
| wikipathways | WP3996 | Ethanol effects on histone modifications |
| wikipathways | WP404 | Nucleotide Metabolism |
| smpdb | SMP00005 | Pterine Biosynthesis |
| smpdb | SMP00053 | Folate Metabolism |
| smpdb | SMP00432 | Methotrexate Action Pathway |
| smpdb | SMP00486 | Dopa-responsive dystonia |
| smpdb | SMP00487 | Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency |
| smpdb | SMP00488 | Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps) |
| smpdb | SMP00489 | Hyperphenylalaninemia due to dhpr-deficiency |
| smpdb | SMP00490 | Segawa syndrome |
| smpdb | SMP00491 | Sepiapterin reductase deficiency |
| smpdb | SMP00543 | Methylenetetrahydrofolate Reductase Deficiency (MTHFRD) |
| smpdb | SMP00724 | Folate malabsorption, hereditary |
| pid | e2f_pathway | E2F transcription factor network |
| pharmgkb | PA165291507 | Fluoropyrimidine Pathway, Pharmacodynamics |
| pharmgkb | PA165291575 | Antimetabolite Pathway - Folate Cycle, Pharmacodynamics |
| pharmgkb | PA2039 | Methotrexate Pathway (Cancer Cell), Pharmacodynamics |
| pharmgkb | PA2040 | Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics |
| biocarta | g1pathway | cell cycle: g1/s check point |
| reactome | R-HSA-1430728 | Metabolism |
| reactome | R-HSA-1430728 | Metabolism |
| reactome | R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-196757 | Metabolism of folate and pterines |
| reactome | R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors |
| reactome | R-HSA-196854 | Metabolism of vitamins and cofactors |
| reactome | R-HSA-196854 | Metabolism of vitamins and cofactors |
| reactome | R-HSA-453279 | Mitotic G1-G1/S phases |
| reactome | R-HSA-539107 | Activation of E2F1 target genes at G1/S |
| reactome | R-HSA-69205 | G1/S-Specific Transcription |
| reactome | R-HSA-69206 | G1/S Transition |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-8978934 | Metabolism of cofactors |
| kegg | hsa00670 | One carbon pool by folate - Homo sapiens (human) |
| kegg | hsa00790 | Folate biosynthesis - Homo sapiens (human) |
| humancyc | PWY66-385 | dTMP de novo biosynthesis (mitochondrial) |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD562 | Navitoclax | 3 |
| iGMDRD780 | PP-30 | 10 |
| iGMDRD100 | Zebularine | 1 |
| iGMDRD730 | Kahalalide F | 4 |
| iGMDRD74 | Idarubicin | 4 |
| iGMDRD23 | Gossypol | 3 |
| iGMDRD598 | QS-11 | 4 |
| iGMDRD268 | Cerulenin | 4 |
| iGMDRD451 | Serdemetan | 5 |
| iGMDRD690 | PRIMA-1MET | 4 |
| iGMDRD369 | TGX-115 | 3 |
| iGMDRD255 | SB225002 | 6 |
| iGMDRD226 | ML006 | 3 |
| iGMDRD801 | 2,4-dideoxy-DC-45-A2 | 5 |
| iGMDRD187 | BRD9876 | 3 |
| iGMDRD316 | N9-Isopropyl-olomoucine | 5 |
| iGMDRD193 | Fqi1 | 3 |
| iGMDRD61 | Kinetin riboside | 3 |
| iGMDRD163 | all trans Retinoic Acid | 5 |
| iGMDRD793 | BEC (hydrochloride) | 4 |
| iGMDRD446 | LY 2183240 | 4 |
| iGMDRD375 | GW-405833 | 4 |
| iGMDRD297 | Austocystin D | 3 |
| iGMDRD466 | Chaetocin | 1 |
| iGMDRD280 | CYTOCHALASIN B | 5 |
| iGMDRD579 | PF750 | 5 |
| iGMDRD425 | ERASTIN | 5 |
| iGMDRD126 | Tipifarnib | 10 |
| iGMDRD781 | Sirolimus | 3 |
| iGMDRD329 | Merck60 | 5 |
| iGMDRD871 | BRD6368 | 3 |
| iGMDRD367 | Ro 28-1675 | 4 |
| iGMDRD872 | BRD7137 | 3 |
| iGMDRD147 | Prima-1 | 5 |
| iGMDRD137 | Indisulam | 2 |
| iGMDRD415 | LE-135 | 4 |
| iGMDRD213 | SMR000068650 | 5 |
| iGMDRD6 | AM-580 | 5 |
| iGMDRD221 | Tamoxifen | 5 |
| iGMDRD192 | CIL56 | 4 |
| iGMDRD536 | PLX-4720 | 1 |
| iGMDRD248 | BRD4354 | 3 |
| iGMDRD307 | Manumycin A | 3 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD532 | Olaparib | 5 |
| iGMDRD150 | RITA | 3 |
| iGMDRD345 | Compound 10b [PMID: 11504634] | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in DHFR
CLASSFICATION
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