======= DHFR =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DHFR
  * **<color #00a2e8>Official Name</color>**: dihydrofolate reductase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1719|1719]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P00374|P00374]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DHFR&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DHFR|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/126060|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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 DHFR2. {ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:21876188}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|DHFR 1|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|dihydrofolate reductase activity|
|dihydrofolate metabolic process|
|methotrexate binding|
|response to methotrexate|
|tetrahydrobiopterin biosynthetic process|
|tetrahydrofolate biosynthetic process|
|tetrahydrobiopterin metabolic process|
|regulation of removal of superoxide radicals|
|folic acid-containing compound biosynthetic process|
|sequence-specific mRNA binding|
|folic acid binding|
|pteridine-containing compound biosynthetic process|
|NADPH binding|
|translation repressor activity, mRNA regulatory element binding|
|response to antimetabolite|
|diol biosynthetic process|
|tetrahydrofolate metabolic process|
|folic acid metabolic process|
|positive regulation of nitric-oxide synthase activity|
|diol metabolic process|
|axon regeneration|
|positive regulation of monooxygenase activity|
|one-carbon metabolic process|
|regulation of transcription involved in G1/S transition of mitotic cell cycle|
|neuron projection regeneration|
|folic acid-containing compound metabolic process|
|regulation of superoxide metabolic process|
|regulation of response to reactive oxygen species|
|pteridine-containing compound metabolic process|
|NADP binding|
|regulation of nitric-oxide synthase activity|
|cellular modified amino acid biosynthetic process|
|response to axon injury|
|positive regulation of oxidoreductase activity|
|regulation of monooxygenase activity|
|drug binding|
|polyol biosynthetic process|
|regulation of cellular response to oxidative stress|
|regulation of response to oxidative stress|
|water-soluble vitamin metabolic process|
|response to antineoplastic agent|
|regulation of oxidoreductase activity|
|dicarboxylic acid metabolic process|
|polyol metabolic process|
|alcohol biosynthetic process|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|vitamin metabolic process|
|negative regulation of translation|
|coenzyme biosynthetic process|
|negative regulation of cellular amide metabolic process|
|regeneration|
|mRNA binding|
|regulation of reactive oxygen species metabolic process|
|organic hydroxy compound biosynthetic process|
|cellular modified amino acid metabolic process|
|cofactor biosynthetic process|
|coenzyme metabolic process|
|mitotic cell cycle phase transition|
|cell cycle phase transition|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|alcohol metabolic process|
|response to acid chemical|
|regulation of translation|
|regulation of cellular amide metabolic process|
|axon development|
|cofactor metabolic process|
|organic hydroxy compound metabolic process|
|drug metabolic process|
|posttranscriptional regulation of gene expression|
|amide biosynthetic process|
|response to wounding|
|small molecule biosynthetic process|
|mitotic cell cycle process|
|neuron projection development|
|mitotic cell cycle|
|regulation of cellular response to stress|
|cellular amide metabolic process|
|neuron development|
|carboxylic acid metabolic process|
|response to organic cyclic compound|
|oxidation-reduction process|
|cell cycle process|
|response to organonitrogen compound|
|oxoacid metabolic process|
|neuron differentiation|
|response to drug|
|organic acid metabolic process|
|negative regulation of cellular protein metabolic process|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|plasma membrane bounded cell projection organization|
|cell projection organization|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|mitochondrion|
|organic cyclic compound biosynthetic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|cell development|
|cellular response to stress|
|negative regulation of gene expression|
|small molecule metabolic process|
|positive regulation of molecular function|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp218|A-395 10μM R05 exp218]]|1.73|
|[[:results:exp292|Menadione 5μM R06 exp292]]|1.76|
|[[:results:exp12|Chloramphenicol 2μM R00 exp12]]|1.79|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|1.8|
|[[:results:exp47|Lapatinib 5μM R01 exp47]]|2.11|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:golga6l6|GOLGA6L6]]|0.477|
|[[:human genes:r:rpl35|RPL35]]|0.455|
|[[:human genes:p:paf1|PAF1]]|0.431|
|[[:human genes:p:plk1|PLK1]]|0.427|
|[[:human genes:c:chd4|CHD4]]|0.422|
|[[:human genes:p:pola1|POLA1]]|0.421|
|[[:human genes:p:polr2j3|POLR2J3]]|0.413|
|[[:human genes:t:tceb3c|TCEB3C]]|0.413|
|[[:human genes:h:hivep3|HIVEP3]]|0.412|
|[[:human genes:s:ssh2|SSH2]]|0.412|
|[[:human genes:n:nup205|NUP205]]|0.412|
|[[:human genes:c:cbwd5|CBWD5]]|0.408|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.407|
|[[:human genes:l:lrr1|LRR1]]|0.406|
|[[:human genes:r:rpl6|RPL6]]|0.404|
|[[:human genes:d:ddtl|DDTL]]|0.402|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.401|
|[[:human genes:r:rrp15|RRP15]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 114/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|7/28|
|blood|9/28|
|bone|2/26|
|breast|10/33|
|central nervous system|3/56|
|cervix|2/4|
|colorectal|2/17|
|esophagus|2/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|4/21|
|liver|2/20|
|lung|17/75|
|lymphocyte|2/16|
|ovary|1/26|
|pancreas|2/24|
|peripheral nervous system|2/16|
|plasma cell|4/15|
|prostate|1/1|
|skin|3/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|4/22|
|urinary tract|6/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 281
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.23 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DHFR Expression in NALM6 Cells: 8.23'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>