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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

DHFR Gene

protein-coding GIFtS: 68
GCID: GC05M079922

dihydrofolate reductase

Explore 101 diseases affiliated with
DHFR via

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DHFR:

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.

(provided by RefSeq, Jul 2008)

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:

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)

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000005.9 NC_018916.1 NT_006713.15

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for DHFR

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DYR_HUMAN, P00374 (See protein sequence)

Recommended Name: Dihydrofolate reductase

Size: 187 amino acids; 21453 Da

Subunit: Homodimer

6/54 PDB 3D structures from and Proteopedia for DHFR (see all 54):

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

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P00374

3 DME Specific Peptides for DHFR (P00374)

QNMGIGK

KQNLVIMG

VLSRELKEPPQGAHFL

DHFR Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000782.1

ENSEMBL proteins:

ENSP00000396308 ENSP00000426474 ENSP00000422732 ENSP00000421334

Reactome Protein details: P00374
Human Recombinant Protein Products:

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	Uscn Proteins for DHFR

Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005575	cellular_component	--	--
GO:0005654	nucleoplasm	--	--
GO:0005829	cytosol	--	--

DHFR for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for DHFR

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

DHFR for domains About GeneDecksing

4 InterPro domains/families:

IPR001796 DHFR_dom

IPR012259 DHFR

IPR024072 DHFR-like_dom

IPR017925 DHFR_CS

Graphical View of Domain Structure for InterPro Entry P00374

ProtoNet protein and cluster: P00374

1 Blocks protein family: IPB001796 Dihydrofolate reductase

UniProtKB/Swiss-Prot: DYR_HUMAN, P00374

Similarity: Belongs to the dihydrofolate reductase family

Similarity: Contains 1 DHFR (dihydrofolate reductase) domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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

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

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		OriGene 3'-UTR Clone: DHFR Browse MicroRNA Expression Plasmids
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Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DHFR

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003729	mRNA binding	--	--
GO:0004146	dihydrofolate reductase activity	--	--
GO:0008144	drug binding	--	--
GO:0050661	NADP binding	--	--

DHFR for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for DHFR:

Decreased circadian period len

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/13 super-pathways (see all 13) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

G1/S-Specific Transcription

	G1/S-Specific Transcription	1.00			E2F mediated regulation of DNA replication	0.45
	Activation of E2F target genes at G1/S	1.00

Metabolism of nitric oxide

	Metabolism of nitric oxide	1.00			Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	0.59
	eNOS activation and regulation	1.00

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics

	Antimetabolite Pathway - Folate Cycle, Pharmacodynamics	1.00			Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics	0.36
	Methotrexate Pathway (Cancer Cell), Pharmacodynamics	0.45

Cell Cycle

Cell Cycle

1.00

Cell Cycle, Mitotic

0.84

Metabolism

Metabolism

1.00

Metabolic pathways

0.38

Pathway sources
See GeneCards unified pathways
Show all pathways

5 BioSystems Pathways for DHFR

	Fluoropyrimidine Activity
	One Carbon Metabolism
	Nucleotide Metabolism
	dTMP de novo biosynthesis
	E2F transcription factor network

5/14 Reactome Pathways for DHFR (see all 14)

	Metabolism of folate and pterines
	eNOS activation and regulation
	Mitotic G1-G1/S phases
	Metabolism
	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

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

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for DHFR

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

5/35 Interacting proteins for DHFR (P00374³ ENSP00000396308⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 35)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
FKBP1A	P62942³, ENSP00000371138⁴	I2D: score=3 STRING: ENSP00000371138
HSPD1	P10809³, ENSP00000340019⁴	I2D: score=3 STRING: ENSP00000340019
ASGR1	P07306³, ENSP00000269299⁴	I2D: score=2 STRING: ENSP00000269299
MDM2	Q00987³, ENSP00000417281⁴	I2D: score=2 STRING: ENSP00000417281
TOMM20	Q15388³, ENSP00000355566⁴	I2D: score=2 STRING: ENSP00000355566

About this table

Gene Ontology (GO): 5/15 biological process terms (GO ID links to tree view) (see all 15): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000082	G1/S transition of mitotic cell cycle	--	--
GO:0000083	regulation of transcription involved in G1/S phase of mitotic cell cycle	--	--
GO:0000278	mitotic cell cycle	--	--
GO:0006545	glycine biosynthetic process	--	--
GO:0006730	one-carbon metabolic process	--	--

DHFR for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

DHFR for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for DHFR available from Tocris Bioscience About this table

Compound	Action	CAS #
Methotrexate	Cytotoxic agent	[59-05-2]
CI 898 trihydrochloride	Dihydrofolate reductase inhibitor	[82952-64-5]

7 HMDB Compounds for DHFR About this table

Compound	Synonyms	CAS #	PubMed Ids
Dihydrobiopterin	(S-(R,S))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone (see all 15)	6779-87-9	3189762
Dihydrofolic acid	7,8-Dihydro-L-folic acid (see all 13)	4033-27-6	--
Dimethyl sulfoxide	(methylsulfinyl)methane;Dimethyl sulfoxide (see all 5)	67-68-5	--
Folic acid	Acifolic (see all 37)	59-30-3	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(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	--

10/27 DrugBank Compounds for DHFR (see all 27) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Pemetrexed	LY231514 (see all 2)	150399-23-8	target	inhibitor	15795320 11742712 14596699 11763166 12571811 11752352 11252887 11531245 12023793 11524555 11848474 11841783
Methotrexate	Amethopterin (see all 12)	59-05-2	target	inhibitor	16971132 17333344 16647263 11752352 17130456 16936229
Methotrexate	Amethopterin (see all 12)	59-05-2	enzyme	substrate	16971132 17333344 16647263 11752352 17130456 16936229 17586865
Trimetrexate	TMQ (see all 4)	52128-35-5	target	inhibitor	10386066 12649191 11752096 10091649 11752352 11448221 12416030
Proguanil	--	500-92-5	target	inhibitor	10068594 12667224 11752352 11295178 10998224 11740746
Trimethoprim	--	738-70-5	target	inhibitor	15561838 11752352 14632594 15115391 15504856 14629008
Pyrimethamine	CD (see all 12)	58-14-0	target	inhibitor	12951104 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

10/127 Novoseek 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

Drug/compound	PharmGKB Annotation
methotrexate	CA

About this table

Search CenterWatch for drugs/clinical trials and news about DHFR / DYR

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 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,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for DHFR gene:

NM_000791.3

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

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat DHFR

Additional cDNA sequence:

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

BC071996.1 J00140.1

19 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.95268392 DT.110960 DT.92455274

24/293 AceView cDNA sequences (see all 293):

AU127142 AA290600 BM833910 AA129464 AI138260 CF136591 AA290577 R00884

BQ644196 BQ650068 BM787874 AA907381 V00507 BU618031 BX364783 AI381187

AI375347 AA974401 AA129465 AI626046 AA447680 CA424783 AA399962 BM459215

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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

DHFR expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AAGGTAACTA

About this image
See DHFR Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for DHFR

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

SABiosciences Expression via Pathway-Focused PCR Array including DHFR:

Cancer Drug Resistance in human mouse rat

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat DHFR

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for DHFR

(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)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for DHFR gene from 9/31 species (see all 31) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Dhfr^{1 , 5}	dihydrofolate reductase^{1, 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	--	--	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	Dhfr^{1 , 3}	'de novo' IMP biosynthesis dihydrofolate reductase³ Dihydrofolate reductase¹	46(a)³ 53.33(n)¹ 48.57(a)¹		89D2³ 42003¹ NM_001043255.1¹ NP_001036720.1¹
worm (Caenorhabditis elegans)	Secernentea	dhfr-1¹	Protein DHFR-1	47.43(n) 36.57(a)		172681 NM_059963.2 NP_492364.1
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	DFR1¹	Dfr1p	46.11(n) 35.56(a)		854411 NP_014879.1
E. coli (Escherichia coli)	Gamma proteobacteria	folA⁶	dihydrofolate reductase	28(a)	1 → many	Chromosome(49823-50302)

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)
About This Section

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

5/7 Pseudogenes.org Pseudogenes for DHFR (see all 7)
PGOHUM00000250460 PGOHUM00000243142 PGOHUM00000243211 PGOHUM00000243224 PGOHUM00000245352

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 5 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1643644^1,2	C,F,	--	75157415(+)	`GAGCGG/TAGATC`	1	--	us2k¹		2	NA WA	4
rs1643645^1,2	C,F,	--	75157423(+)	`ATCGCG/ACCACT`	1	--	us2k¹		2	NA WA	4
rs115707956^1,2	C,	--	75157924(+)	`TTTGAG/TACTGG`	1	--	us2k¹		1	NA	120
rs1677626^1,2	C,F,A,H,	--	75158329(+)	`AATTCG/CAGATC`	1	--	us2k¹		26	MN NS EA NA WA	2834
rs1478834^1,2	C,F,A,H,	--	75158459(+)	`GTGCTC/AACCTC`	1	--	us2k¹		20	MN NS EA NA WA	2518
rs1478835^1,2	C,F,	--	75158484(+)	`CCCAGC/TTGCCA`	1	--	us2k¹		8	MN NA WA EA	550
rs6151593^1,2	C	--	75158687(+)	`AAGCAA/CGACCC`	1	--	us2k¹		2	NS NA	178
rs6151594^1,2	C,	--	75158850(+)	`TAGGGG/ATGAGG`	1	--	us2k¹		1	NS	176
rs10168^1,2	C,F,	--	75159306(-)	`CAAATG/AGGGAC`	1	--	us2k¹		2	NS WA	206
rs1677658^1,2	C,F,	--	75159780(+)	`AGGCGG/TGGACC`	1	--	int¹		3	NS NA	300

HapMap Linkage Disequilibrium report for DHFR (79922045 - 79950802 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 6 variations for DHFR
6 CNVs: 80962 64240 32727 93110 69154 0065
Human Gene Mutation Database (HGMD): DHFR

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing DHFR

DNA2.0 Custom Variant and Variant Library Synthesis for DHFR

(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.)
About This Section

DHFR for disorders About GeneDecksing

OMIM gene information: 126060 OMIM disorders: --

UniProtKB/Swiss-Prot: DYR_HUMAN, P00374

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

20/101 diseases for DHFR (see all 101): About MalaCards

megaloblastic anemia anemia, megaloblastic, due to dhfr deficiency megaloblastic anemia due to dihydrofolate reductase deficiency anemia

homocysteine plasma level candida glabrata neural tube defect xeroderma pigmentosum

patent ductus arteriosus spina bifida childhood absence epilepsy absence epilepsy

plasmodium falciparum malaria cerebral folate deficiency malignant pleural mesothelioma isosporiasis

squamous cell carcinoma cryptosporidiosis soft tissue sarcoma birth defects

4 diseases from the University of Copenhagen DISEASES database for DHFR:

Malaria Pneumocystosis Leukemia Cryptosporidiosis

10/81 Novoseek 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)
About This Section

PubMed articles for DHFR gene, integrated from 9 sources (see all 1091):
(articles sorted by number of sources associating them with DHFR)

Utopia: connect your pdf to the dynamic
world of online information

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. (1992)
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. (2005)
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. (1997)
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. (2009)
A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression. (PubMed id 11448909)^{1, 4, 9} Goto Y....Saikawa Y. (2001)
Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. (PubMed id 2248959)^{1, 2, 9} Davies J.F.... Kraut J. (1990)
Dihydrofolate reductase deficiency due to a homozygou s DHFR mutation causes megaloblastic anemia and cerebral folate deficiency lead ing to severe neurologic disease. (PubMed id 21310277)^{1, 2} Cario H....Schwarz K. (2011)
Identification and characterization of an inborn erro r of metabolism caused by dihydrofolate reductase deficiency. (PubMed id 21310276)^{1, 2} Banka S....Newman W.G. (2011)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. (PubMed id 15039552)^{1, 2} Cody V.... Queener S.F. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
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)
About This Section

Entrez Gene: 1719	HGNC: 2861	AceView: DHFR	Ensembl:ENSG00000228716	euGenes: HUgn1719
ECgene: DHFR	Kegg: 1719	H-InvDB: DHFR

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
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

Intellectual Property for DHFR gene
(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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dihydrofolate reductase

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