Aliases for DHFR2 Gene

Aliases for DHFR2 Gene

  • Dihydrofolate Reductase 2 2 3 5
  • Dihydrofolate Reductase 2, Mitochondrial 3 4
  • Dihydrofolate Reductase, Mitochondrial 3 4
  • Dihydrofolate Reductase-Like Protein 1 3 4
  • Dihydrofolate Reductase Pseudogene 4 2 3
  • Dihydrofolate Reductase Like 1 2 3
  • EC 4 50
  • DHFRL1 3 4
  • DHFRP4 3 4
  • Dihydrofolate Reductase-Like 1 2
  • FLJ16119 2
  • DHFR2 5

External Ids for DHFR2 Gene

Previous HGNC Symbols for DHFR2 Gene

  • DHFRP4
  • DHFRL1

Summaries for DHFR2 Gene

GeneCards Summary for DHFR2 Gene

DHFR2 (Dihydrofolate Reductase 2) is a Protein Coding gene. Diseases associated with DHFR2 include Cystoisosporiasis. Among its related pathways are One carbon pool by folate and Metabolism of water-soluble vitamins and cofactors. An important paralog of this gene is DHFR.

UniProtKB/Swiss-Prot Summary for DHFR2 Gene

  • Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DHFR2 Gene

Genomics for DHFR2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DHFR2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J094061 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 254.2 +0.1 104 3.1 MYC ZNF580 POLR2A ATF3 BRCA1 YY1 SMAD5 SIN3A ELK1 ETS1 STX19 DHFR2 HSALNG0027338 NSUN3 lnc-DHFR2-1
GH03J093979 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.7 +82.6 82589 2.8 SP1 ZNF207 ZNF600 IKZF1 POLR2A BRCA1 YY1 MXD4 KLF11 SMAD5 ARL13B HSALNG0027333 PROS1 NSUN3 RBBP4P2 DHFR2 lnc-PROS1-1 STX19
GH03J094028 Promoter/Enhancer 1 EPDnew Ensembl ENCODE 11.5 +34.8 34835 0.8 JUND ELF1 CTBP1 ZBTB40 ZNF217 SMARCE1 DPF2 EP300 STX19 DHFR2 NSUN3 HSALNG0027335 ARL13B
GH03J094004 Enhancer 0.7 ENCODE 11.6 +58.9 58908 0.6 ZNF654 CTCF REST TRIM22 KMT2B IRF2 RAD21 IRF4 RFX5 SMC3 NSUN3 DHFR2 HSALNG0027335 ARL13B STX19
GH03J094098 Enhancer 0.5 Ensembl 10.8 -35.0 -35012 2.8 ATF2 FOXA2 CTCF SPI1 POLR2A FOXA1 ATF7 ZBTB44 NSUN3 DHFR2 PROS1 HSALNG0027339 HSALNG0027346
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DHFR2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DHFR2

Genomic Locations for DHFR2 Gene

Latest Assembly
15,554 bases
Minus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
4,995 bases
Minus strand

(GRCh37/hg19 by Ensembl)
15,554 bases
Minus strand

Genomic View for DHFR2 Gene

Genes around DHFR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DHFR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DHFR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DHFR2 Gene

Proteins for DHFR2 Gene

  • Protein details for DHFR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Dihydrofolate reductase 2, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • D3DN30
    • Q6P4I9

    Protein attributes for DHFR2 Gene

    187 amino acids
    Molecular mass:
    21620 Da
    Quaternary structure:
    No Data Available
    • Humans have acquired two dihydrofolate reductase enzymes during their evolution, DHFR and DHFR2. In contrast to human, mice and brown rats have just one.

neXtProt entry for DHFR2 Gene

Selected DME Specific Peptides for DHFR2 Gene


Post-translational modifications for DHFR2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DHFR2 Gene

Domains & Families for DHFR2 Gene

Gene Families for DHFR2 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for DHFR2 Gene

  • Dihydrofolate reductase

Suggested Antigen Peptide Sequences for DHFR2 Gene

GenScript: Design optimal peptide antigens:
  • Dihydrofolate reductase-like protein 1 (DYRL1_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the dihydrofolate reductase family.
  • Belongs to the dihydrofolate reductase family.
genes like me logo Genes that share domains with DHFR2: view

Function for DHFR2 Gene

Molecular function for DHFR2 Gene

UniProtKB/Swiss-Prot Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378, ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=; Evidence={ECO:0000255|PROSITE-ProRule:PRU00660, ECO:0000269|PubMed:21876184};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=209 uM for dihydrofolate {ECO:0000269|PubMed:21876184}; KM=20 uM for NADPH {ECO:0000269|PubMed:21876184};

Enzyme Numbers (IUBMB) for DHFR2 Gene

Phenotypes From GWAS Catalog for DHFR2 Gene

Gene Ontology (GO) - Molecular Function for DHFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003729 mRNA binding IDA 21876184
GO:0004146 dihydrofolate reductase activity IEA,IMP 21876188
GO:0016491 oxidoreductase activity IEA --
GO:0050661 NADP binding IEA,IBA 21873635
genes like me logo Genes that share ontologies with DHFR2: view
genes like me logo Genes that share phenotypes with DHFR2: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DHFR2

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for DHFR2 Gene

Localization for DHFR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DHFR2 Gene

Mitochondrion. Mitochondrion matrix. Mitochondrion inner membrane.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DHFR2 gene
Compartment Confidence
mitochondrion 5
nucleus 2
plasma membrane 1
extracellular 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for DHFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IDA 21876184
GO:0005743 mitochondrial inner membrane IMP 21876188
GO:0005759 mitochondrial matrix IMP 21876188
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with DHFR2: view

Pathways & Interactions for DHFR2 Gene

genes like me logo Genes that share pathways with DHFR2: view

UniProtKB/Swiss-Prot Q86XF0-DYR2_HUMAN

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

Gene Ontology (GO) - Biological Process for DHFR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006545 glycine biosynthetic process IEA --
GO:0006730 one-carbon metabolic process IEA --
GO:0046105 thymidine biosynthetic process IDA 21876188
GO:0046452 dihydrofolate metabolic process IBA 21873635
GO:0046653 tetrahydrofolate metabolic process IDA 21876184
genes like me logo Genes that share ontologies with DHFR2: view

No data available for SIGNOR curated interactions for DHFR2 Gene

Drugs & Compounds for DHFR2 Gene

(18) Drugs for DHFR2 Gene - From: DrugBank, ApexBio, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR 1884
Pralatrexate Approved, Investigational Pharma Antifolate,a folate analog, RFC-1 targeted DHFR inhibitor 0
Folic acid Approved, Vet_approved Nutra 5007
NADH Approved Nutra 0
5-(4-Methoxyphenoxy)-2,4-Quinazolinediamine Experimental Pharma Target 0

(1) Additional Compounds for DHFR2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • H+
  • H(+)
  • Hydron
  • Hydrogen cation
  • Proton

(2) ApexBio Compounds for DHFR2 Gene

Compound Action Cas Number
Methotrexate Folate antagonist,inhibits DFHR 1959-05-2
Pralatrexate Antifolate,a folate analog 146464-95-1
genes like me logo Genes that share compounds with DHFR2: view

Drug products for research

Transcripts for DHFR2 Gene

mRNA/cDNA for DHFR2 Gene

5 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DHFR2

Alternative Splicing Database (ASD) splice patterns (SP) for DHFR2 Gene

No ASD Table

Relevant External Links for DHFR2 Gene

GeneLoc Exon Structure for

Expression for DHFR2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DHFR2

mRNA Expression by UniProt/SwissProt for DHFR2 Gene:

Tissue specificity: Expressed in numerous cell lines.

Evidence on tissue expression from TISSUES for DHFR2 Gene

  • Nervous system(4.5)
  • Muscle(4.2)

Primer products for research

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for DHFR2 Gene

Orthologs for DHFR2 Gene

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

Orthologs for DHFR2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia DHFRL1 29 30
  • 99.28 (n)
(Canis familiaris)
Mammalia -- 30
  • 88 (a)
-- 30
  • 84 (a)
(Mus musculus)
Mammalia Dhfr 30
  • 87 (a)
(Bos Taurus)
Mammalia DHFR 30
  • 83 (a)
(Monodelphis domestica)
Mammalia -- 30
  • 78 (a)
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 60 (a)
(Gallus gallus)
Aves DHFR 30
  • 68 (a)
(Anolis carolinensis)
Reptilia -- 30
  • 71 (a)
(Danio rerio)
Actinopterygii dhfr 30
  • 57 (a)
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8788 29
Fruit Fly
(Drosophila melanogaster)
Insecta Dhfr 30
  • 46 (a)
(Caenorhabditis elegans)
Secernentea dhfr-1 30
  • 32 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes DFR1 30
  • 29 (a)
Species where no ortholog for DHFR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • Fission Yeast (Schizosaccharomyces pombe)
  • 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)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for DHFR2 Gene

Gene Tree for DHFR2 (if available)
Gene Tree for DHFR2 (if available)
Evolutionary constrained regions (ECRs) for DHFR2: view image
Alliance of Genome Resources:
Additional Orthologs for DHFR2

Paralogs for DHFR2 Gene

Paralogs for DHFR2 Gene Pseudogenes for DHFR2 Gene

genes like me logo Genes that share paralogs with DHFR2: view

Variants for DHFR2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DHFR2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs17855824 -- p.Val166Ile

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for DHFR2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for DHFR2 Gene

Variant ID Type Subtype PubMed ID
esv3893746 CNV loss 25118596
nsv590987 CNV loss 21841781
nsv963340 CNV duplication 23825009

Variation tolerance for DHFR2 Gene

Residual Variation Intolerance Score: 53.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.35; 76.80% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DHFR2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DHFR2 Gene

Disorders for DHFR2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for DHFR2 Gene - From: COP

Disorder Aliases PubMed IDs
  • infection by isospora belli and isospora hominis
- elite association - COSMIC cancer census association via MalaCards
Search DHFR2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DHFR2

genes like me logo Genes that share disorders with DHFR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DHFR2 Gene

Publications for DHFR2 Gene

  1. An active second dihydrofolate reductase enzyme is not a feature of rat and mouse, but they do have activity in their mitochondria. (PMID: 25980602) Hughes L … Parle-McDermott A (FEBS letters 2015) 2 3 4
  2. The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional. (PMID: 21876184) McEntee G … Parle-McDermott A (Proceedings of the National Academy of Sciences of the United States of America 2011) 2 3 4
  3. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. (PMID: 21876188) Anderson DD … Stover PJ (Proceedings of the National Academy of Sciences of the United States of America 2011) 3 4
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. Architecture of the human interactome defines protein communities and disease networks. (PMID: 28514442) Huttlin EL … Harper JW (Nature 2017) 3

Products for DHFR2 Gene

Sources for DHFR2 Gene