Human Gene DHFR (ENST00000439211.7_7) from GENCODE V47lift37
  Description: dihydrofolate reductase, transcript variant 1 (from RefSeq NM_000791.4)
Gencode Transcript: ENST00000439211.7_7
Gencode Gene: ENSG00000228716.7_10
Transcript (Including UTRs)
   Position: hg19 chr5:79,922,045-79,950,802 Size: 28,758 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg19 chr5:79,924,906-79,950,308 Size: 25,403 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:79,922,045-79,950,802)mRNA (may differ from genome)Protein (187 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: DYR_HUMAN
DESCRIPTION: RecName: Full=Dihydrofolate reductase; EC=1.5.1.3;
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;
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
SUBUNIT: Homodimer.
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.
DISEASE: Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]. DHFRD is 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.
SIMILARITY: Belongs to the dihydrofolate reductase family.
SIMILARITY: Contains 1 DHFR (dihydrofolate reductase) domain.
WEB RESOURCE: Name=Wikipedia; Note=Dihydrofolate reductase entry; URL="http://en.wikipedia.org/wiki/Dihydrofolate_reductase";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: DHFR
Diseases sorted by gene-association score: megaloblastic anemia due to dihydrofolate reductase deficiency* (1681), plasmodium falciparum malaria (20), cerebral folate deficiency (20), tetrahydrobiopterin deficiency (20), megaloblastic anemia (19), pediatric osteosarcoma (16), plasmodium malariae malaria (15), candida glabrata (13), pneumocystosis (12), pancytopenia (12), toxoplasmosis (8), cryptosporidiosis (8), unilateral retinoblastoma (8), myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency (6), transcobalamin ii deficiency (4), malaria (4), neural tube defects (3), lung cancer (2), osteosarcoma, somatic (2), childhood absence epilepsy (2), parasitic protozoa infectious disease (1), leukemia, acute lymphoblastic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.38 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 119.91 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -257.00494-0.520 Picture PostScript Text
3' UTR -859.102861-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012259 - DHFR
IPR024072 - DHFR-like_dom
IPR017925 - DHFR_CS
IPR001796 - DHFR_dom

Pfam Domains:
PF00186 - Dihydrofolate reductase

SCOP Domains:
53597 - Dihydrofolate reductase-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1BOZ - X-ray 1DHF - X-ray MuPIT 1DLR - X-ray MuPIT 1DLS - X-ray MuPIT 1DRF - X-ray MuPIT 1HFP - X-ray MuPIT 1HFQ - X-ray MuPIT 1HFR - X-ray MuPIT 1KMS - X-ray MuPIT 1KMV - X-ray MuPIT 1MVS - X-ray MuPIT 1MVT - X-ray MuPIT 1OHJ - X-ray MuPIT 1OHK - X-ray MuPIT 1PD8 - X-ray MuPIT 1PD9 - X-ray MuPIT 1PDB - X-ray MuPIT 1S3U - X-ray MuPIT 1S3V - X-ray MuPIT 1S3W - X-ray MuPIT 1U71 - X-ray MuPIT 1U72 - X-ray MuPIT 1YHO - NMR MuPIT 2C2S - X-ray MuPIT 2C2T - X-ray MuPIT 2DHF - X-ray MuPIT 2W3A - X-ray MuPIT 2W3B - X-ray MuPIT 2W3M - X-ray MuPIT 3EIG - X-ray MuPIT 3F8Y - X-ray MuPIT 3F8Z - X-ray MuPIT 3F91 - X-ray MuPIT 3FS6 - X-ray MuPIT 3GHC - X-ray MuPIT 3GHV - X-ray MuPIT 3GHW - X-ray MuPIT 3GI2 - X-ray MuPIT 3GYF - X-ray MuPIT 3L3R - X-ray MuPIT 3N0H - X-ray MuPIT 3NTZ - X-ray MuPIT 3NU0 - X-ray MuPIT 3NXO - X-ray MuPIT 3NXR - X-ray MuPIT 3NXT - X-ray MuPIT 3NXV - X-ray MuPIT 3NXX - X-ray MuPIT 3NXY - X-ray MuPIT 3NZD - X-ray MuPIT 3OAF - X-ray MuPIT 3S3V - X-ray MuPIT 3S7A - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P00374
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000900 translation repressor activity, nucleic acid binding
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0004146 dihydrofolate reductase activity
GO:0005542 folic acid binding
GO:0008144 drug binding
GO:0016491 oxidoreductase activity
GO:0033560 folate reductase activity
GO:0051870 methotrexate binding
GO:0070402 NADPH binding
GO:1990825 sequence-specific mRNA binding

Biological Process:
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0006729 tetrahydrobiopterin biosynthetic process
GO:0006730 one-carbon metabolic process
GO:0017148 negative regulation of translation
GO:0031103 axon regeneration
GO:0031427 response to methotrexate
GO:0046452 dihydrofolate metabolic process
GO:0046653 tetrahydrofolate metabolic process
GO:0046654 tetrahydrofolate biosynthetic process
GO:0046655 folic acid metabolic process
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0055114 oxidation-reduction process
GO:2000121 regulation of removal of superoxide radicals

Cellular Component:
GO:0005575 cellular_component
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  LF384941 - JP 2014500723-A/192444: Polycomb-Associated Non-Coding RNAs.
BC009634 - Homo sapiens, clone IMAGE:3891285, mRNA.
JD536879 - Sequence 517903 from Patent EP1572962.
JD331311 - Sequence 312335 from Patent EP1572962.
JD196870 - Sequence 177894 from Patent EP1572962.
JD043694 - Sequence 24718 from Patent EP1572962.
JD280071 - Sequence 261095 from Patent EP1572962.
JD490008 - Sequence 471032 from Patent EP1572962.
BC000192 - Homo sapiens dihydrofolate reductase, mRNA (cDNA clone MGC:857 IMAGE:3352539), complete cds.
JD103193 - Sequence 84217 from Patent EP1572962.
JD516797 - Sequence 497821 from Patent EP1572962.
JD554041 - Sequence 535065 from Patent EP1572962.
JD319528 - Sequence 300552 from Patent EP1572962.
JD442794 - Sequence 423818 from Patent EP1572962.
JD532190 - Sequence 513214 from Patent EP1572962.
JD558692 - Sequence 539716 from Patent EP1572962.
JD175060 - Sequence 156084 from Patent EP1572962.
JD472202 - Sequence 453226 from Patent EP1572962.
JD079480 - Sequence 60504 from Patent EP1572962.
JD250882 - Sequence 231906 from Patent EP1572962.
JD345960 - Sequence 326984 from Patent EP1572962.
JD341169 - Sequence 322193 from Patent EP1572962.
JD540086 - Sequence 521110 from Patent EP1572962.
JD240058 - Sequence 221082 from Patent EP1572962.
JD366188 - Sequence 347212 from Patent EP1572962.
JD189764 - Sequence 170788 from Patent EP1572962.
JD269554 - Sequence 250578 from Patent EP1572962.
JD230002 - Sequence 211026 from Patent EP1572962.
JD281956 - Sequence 262980 from Patent EP1572962.
JD296383 - Sequence 277407 from Patent EP1572962.
JD093045 - Sequence 74069 from Patent EP1572962.
JD184170 - Sequence 165194 from Patent EP1572962.
JD045176 - Sequence 26200 from Patent EP1572962.
JD121984 - Sequence 103008 from Patent EP1572962.
JD456688 - Sequence 437712 from Patent EP1572962.
JD335160 - Sequence 316184 from Patent EP1572962.
JD442822 - Sequence 423846 from Patent EP1572962.
JD558699 - Sequence 539723 from Patent EP1572962.
JD315171 - Sequence 296195 from Patent EP1572962.
JD335159 - Sequence 316183 from Patent EP1572962.
JD114005 - Sequence 95029 from Patent EP1572962.
JD497474 - Sequence 478498 from Patent EP1572962.
JD050120 - Sequence 31144 from Patent EP1572962.
JD482697 - Sequence 463721 from Patent EP1572962.
JD277642 - Sequence 258666 from Patent EP1572962.
JD294352 - Sequence 275376 from Patent EP1572962.
JD372272 - Sequence 353296 from Patent EP1572962.
JD117928 - Sequence 98952 from Patent EP1572962.
JD430827 - Sequence 411851 from Patent EP1572962.
JD512746 - Sequence 493770 from Patent EP1572962.
JD412781 - Sequence 393805 from Patent EP1572962.
JD197804 - Sequence 178828 from Patent EP1572962.
JD212410 - Sequence 193434 from Patent EP1572962.
JD542554 - Sequence 523578 from Patent EP1572962.
JD052936 - Sequence 33960 from Patent EP1572962.
JD244053 - Sequence 225077 from Patent EP1572962.
JD239949 - Sequence 220973 from Patent EP1572962.
JD346666 - Sequence 327690 from Patent EP1572962.
JD414963 - Sequence 395987 from Patent EP1572962.
JD312185 - Sequence 293209 from Patent EP1572962.
JD069784 - Sequence 50808 from Patent EP1572962.
JD495447 - Sequence 476471 from Patent EP1572962.
JD056152 - Sequence 37176 from Patent EP1572962.
JD264433 - Sequence 245457 from Patent EP1572962.
JD341521 - Sequence 322545 from Patent EP1572962.
JD341619 - Sequence 322643 from Patent EP1572962.
JD139564 - Sequence 120588 from Patent EP1572962.
JD139565 - Sequence 120589 from Patent EP1572962.
JD310513 - Sequence 291537 from Patent EP1572962.
JD533841 - Sequence 514865 from Patent EP1572962.
AK297302 - Homo sapiens cDNA FLJ51500 complete cds, highly similar to Dihydrofolate reductase (EC 1.5.1.3).
JD467766 - Sequence 448790 from Patent EP1572962.
JD480901 - Sequence 461925 from Patent EP1572962.
JD407923 - Sequence 388947 from Patent EP1572962.
JD322134 - Sequence 303158 from Patent EP1572962.
JD562098 - Sequence 543122 from Patent EP1572962.
JD262501 - Sequence 243525 from Patent EP1572962.
JD457327 - Sequence 438351 from Patent EP1572962.
JD154315 - Sequence 135339 from Patent EP1572962.
JD198804 - Sequence 179828 from Patent EP1572962.
JD293210 - Sequence 274234 from Patent EP1572962.
JD293209 - Sequence 274233 from Patent EP1572962.
JD234134 - Sequence 215158 from Patent EP1572962.
JD563373 - Sequence 544397 from Patent EP1572962.
AK293146 - Homo sapiens cDNA FLJ53008 complete cds, highly similar to Dihydrofolate reductase (EC 1.5.1.3).
JD453738 - Sequence 434762 from Patent EP1572962.
JD507923 - Sequence 488947 from Patent EP1572962.
JD295800 - Sequence 276824 from Patent EP1572962.
LF332231 - JP 2014500723-A/139734: Polycomb-Associated Non-Coding RNAs.
JA125460 - Sequence 24 from Patent EP2300017.
AK308492 - Homo sapiens cDNA, FLJ98533.
JD539421 - Sequence 520445 from Patent EP1572962.
JD308473 - Sequence 289497 from Patent EP1572962.
JD315114 - Sequence 296138 from Patent EP1572962.
JD081753 - Sequence 62777 from Patent EP1572962.
J00140 - Human dihydrofolate reductase gene.
BC070280 - Homo sapiens dihydrofolate reductase, mRNA (cDNA clone MGC:88273 IMAGE:6714220), complete cds.
JD282718 - Sequence 263742 from Patent EP1572962.
JD180594 - Sequence 161618 from Patent EP1572962.
JD241069 - Sequence 222093 from Patent EP1572962.
BC003584 - Homo sapiens dihydrofolate reductase, mRNA (cDNA clone MGC:3153 IMAGE:3354190), complete cds.
BC071996 - Homo sapiens dihydrofolate reductase, mRNA (cDNA clone MGC:88697 IMAGE:4645596), complete cds.
JD146584 - Sequence 127608 from Patent EP1572962.
EU145592 - Homo sapiens dihydrofolate reductase (DHFR) mRNA, complete cds.
V00507 - Human mRNA for dihydrofolic acid reductase (coding region only).
AK312642 - Homo sapiens cDNA, FLJ93028, Homo sapiens dihydrofolate reductase (DHFR), mRNA.
KJ891049 - Synthetic construct Homo sapiens clone ccsbBroadEn_00443 DHFR gene, encodes complete protein.
DQ892816 - Synthetic construct clone IMAGE:100005446; FLH189989.01X; RZPDo839D0475D dihydrofolate reductase (DHFR) gene, encodes complete protein.
CU674082 - Synthetic construct Homo sapiens gateway clone IMAGE:100017996 5' read DHFR mRNA.
AB590112 - Synthetic construct DNA, clone: pFN21AE1342, Homo sapiens DHFR gene for dihydrofolate reductase, without stop codon, in Flexi system.
DQ896062 - Synthetic construct Homo sapiens clone IMAGE:100010522; FLH189987.01L; RZPDo839D0465D dihydrofolate reductase (DHFR) gene, encodes complete protein.
JD024132 - Sequence 5156 from Patent EP1572962.
JD031467 - Sequence 12491 from Patent EP1572962.
JD036068 - Sequence 17092 from Patent EP1572962.
JD461936 - Sequence 442960 from Patent EP1572962.
JD217619 - Sequence 198643 from Patent EP1572962.
JD404905 - Sequence 385929 from Patent EP1572962.
JD399204 - Sequence 380228 from Patent EP1572962.
JD351917 - Sequence 332941 from Patent EP1572962.
LF332222 - JP 2014500723-A/139725: Polycomb-Associated Non-Coding RNAs.
MA620518 - JP 2018138019-A/192444: Polycomb-Associated Non-Coding RNAs.
MA567808 - JP 2018138019-A/139734: Polycomb-Associated Non-Coding RNAs.
MA567799 - JP 2018138019-A/139725: Polycomb-Associated Non-Coding RNAs.
MP014926 - Sequence 129 from Patent WO2019016252.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_g1Pathway - Cell Cycle: G1/S Check Point

Reactome (by CSHL, EBI, and GO)

Protein P00374 (Reactome details) participates in the following event(s):

R-HSA-1497794 Salvage - BH2 is reduced to BH4 by DHFR
R-HSA-197963 Folate is reduced to dihydrofolate (DHF)
R-HSA-197972 DHF is reduced to tetrahydrofolate (THF)
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-69205 G1/S-Specific Transcription
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-196757 Metabolism of folate and pterines
R-HSA-69206 G1/S Transition
R-HSA-8978934 Metabolism of cofactors
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1430728 Metabolism
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: B4DDD2, DYR_HUMAN, ENST00000439211.1, ENST00000439211.2, ENST00000439211.3, ENST00000439211.4, ENST00000439211.5, ENST00000439211.6, NM_000791, P00374, Q14130, Q6IRW8, uc320hkn.1, uc320hkn.2
UCSC ID: ENST00000439211.7_7
RefSeq Accession: NM_000791.4
Protein: P00374 (aka DYR_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.