Details for: DHFR

Gene ID: 1719

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DHFR

Ensembl ID: ENSG00000228716

Description: dihydrofolate reductase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • precursor B cell CL0000817
    CSI 33.67
    rCSI 29.49%
    PRS 88.89
  • cardiac muscle cell CL0000746
    CSI 29.87
    rCSI 42.87%
    PRS 72.67
  • fallopian tube secretory epithelial cell CL4030006
    CSI 13.77
    rCSI 13.26%
    PRS 81.86
  • blood vessel endothelial cell CL0000071
    CSI 12.95
    rCSI 26.88%
    PRS 79.36
  • large pre-B-II cell CL0000957
    CSI 12.73
    rCSI 36.35%
    PRS 86.78
  • Hofbauer cell CL3000001
    CSI 11.54
    rCSI 21.79%
    PRS 89.44
  • intestine goblet cell CL0019031
    CSI 11.08
    rCSI 9.83%
    PRS 80.26
  • choroid plexus epithelial cell CL0000706
    CSI 11
    rCSI 18.02%
    PRS 72.38
  • erythrocyte CL0000232
    CSI 9.99
    rCSI 22.67%
    PRS 82.62
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 9.76
    rCSI 11.79%
    PRS 89.17
  • interstitial cell of Cajal CL0002088
    CSI 9.65
    rCSI 12.29%
    PRS 87.17
  • extravillous trophoblast CL0008036
    CSI 9.21
    rCSI 11.39%
    PRS 80.64
  • perivascular cell CL4033054
    CSI 9.04
    rCSI 12.35%
    PRS 86.68
  • goblet cell CL0000160
    CSI 8.96
    rCSI 8.46%
    PRS 80.87
  • radial glial cell CL0000681
    CSI 8.49
    rCSI 11.8%
    PRS 80.8
  • neural crest cell CL0011012
    CSI 8.24
    rCSI 6.51%
    PRS 72.1
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 6.95
    rCSI 6.28%
    PRS 80.76
  • transit amplifying cell of small intestine CL0009012
    CSI 6.84
    rCSI 30.03%
    PRS 89.17
  • transit amplifying cell of colon CL0009011
    CSI 6.53
    rCSI 7.67%
    PRS 83.9
  • cardiac blood vessel endothelial cell CL0010006
    CSI 6.53
    rCSI 46.18%
    PRS 75.45
  • hepatic stellate cell CL0000632
    CSI 6.3
    rCSI 23.61%
    PRS 75.34
  • pro-B cell CL0000826
    CSI 6.19
    rCSI 5.13%
    PRS 84.5
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 6.07
    rCSI 7.01%
    PRS 74.74
  • common myeloid progenitor CL0000049
    CSI 5.84
    rCSI 4.72%
    PRS 84.55
  • primitive red blood cell CL0002355
    CSI 5.73
    rCSI 30.94%
    PRS 87.63
  • common dendritic progenitor CL0001029
    CSI 5.52
    rCSI 6.93%
    PRS 89.87
  • erythroblast CL0000765
    CSI 5.33
    rCSI 14.14%
    PRS 87.01
  • plasmablast CL0000980
    CSI 5.25
    rCSI 4.13%
    PRS 86.92
  • colon epithelial cell CL0011108
    CSI 5.08
    rCSI 5.32%
    PRS 79.93
  • endothelial cell of placenta CL0009092
    CSI 4.8
    rCSI 23.68%
    PRS 89.04
  • endocardial cell CL0002350
    CSI 4.77
    rCSI 22.86%
    PRS 78.8
  • transit amplifying cell CL0009010
    CSI 4.56
    rCSI 6.97%
    PRS 89.53
  • pericyte CL0000669
    CSI 4.51
    rCSI 12.01%
    PRS 60.47
  • early lymphoid progenitor CL0000936
    CSI 4.03
    rCSI 3.54%
    PRS 87.2
  • multi-ciliated epithelial cell CL0005012
    CSI 4
    rCSI 3.99%
    PRS 76.46
  • glioblast CL0000030
    CSI 3.91
    rCSI 6.23%
    PRS 74.11
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.72
    rCSI 4.62%
    PRS 63.07
  • fraction A pre-pro B cell CL0002045
    CSI 3.69
    rCSI 4.22%
    PRS 91.33
  • cerebral cortex neuron CL0010012
    CSI 3.67
    rCSI 14.95%
    PRS 74.32
  • intestinal epithelial cell CL0002563
    CSI 3.51
    rCSI 3.66%
    PRS 80.06
  • midzonal region hepatocyte CL0019028
    CSI 3.44
    rCSI 8.08%
    PRS 82.05
  • promyelocyte CL0000836
    CSI 3.37
    rCSI 4.86%
    PRS 87.45
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.37
    rCSI 2.92%
    PRS 86.18
  • periportal region hepatocyte CL0019026
    CSI 3.34
    rCSI 12.97%
    PRS 81.48
  • mature astrocyte CL0002627
    CSI 3.32
    rCSI 14.1%
    PRS 74.95
  • epithelial cell of lung CL0000082
    CSI 3.3
    rCSI 2.74%
    PRS 83.41
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.28
    rCSI 3.92%
    PRS 65.29
  • bronchus fibroblast of lung CL2000093
    CSI 3.21
    rCSI 2.6%
    PRS 81.91
  • stem cell CL0000034
    CSI 3.03
    rCSI 2.92%
    PRS 76.45
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.99
    rCSI 2.09%
    PRS 85.9
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.9
    rCSI 3.72%
    PRS 78.58
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.86
    rCSI 6.85%
    PRS 69.54
  • Kupffer cell CL0000091
    CSI 2.79
    rCSI 6.37%
    PRS 83.22
  • inhibitory interneuron CL0000498
    CSI 2.66
    rCSI 6.13%
    PRS 70.79
  • promonocyte CL0000559
    CSI 2.55
    rCSI 4.36%
    PRS 87.64
  • elicited macrophage CL0000861
    CSI 2.52
    rCSI 2.32%
    PRS 89.36
  • placental villous trophoblast CL2000060
    CSI 2.5
    rCSI 3.86%
    PRS 81.5
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.25
    rCSI 6.94%
    PRS 86.23
  • erythroid lineage cell CL0000764
    CSI 2.23
    rCSI 14.34%
    PRS 89.77
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.21
    rCSI 53.39%
    PRS 63.73
  • adipocyte CL0000136
    CSI 2.2
    rCSI 2.83%
    PRS 72.87
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.16
    rCSI 2.2%
    PRS 90.8
  • direct pathway medium spiny neuron CL4023026
    CSI 2.14
    rCSI 51.12%
    PRS 63.15
  • mesodermal cell CL0000222
    CSI 2.1
    rCSI 2.52%
    PRS 80.55
  • hepatocyte CL0000182
    CSI 2.1
    rCSI 3.75%
    PRS 81.74
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.03
    rCSI 17.51%
    PRS 76.82
  • chondrocyte CL0000138
    CSI 1.88
    rCSI 2.99%
    PRS 75.92
  • Schwann cell CL0002573
    CSI 1.85
    rCSI 5.27%
    PRS 78.1
  • fibroblast CL0000057
    CSI 1.85
    rCSI 5.31%
    PRS 76.29
  • common lymphoid progenitor CL0000051
    CSI 1.79
    rCSI 2.4%
    PRS 94.67
  • renal principal cell CL0005009
    CSI 1.79
    rCSI 4.65%
    PRS 82.55
  • respiratory basal cell CL0002633
    CSI 1.76
    rCSI 1.82%
    PRS 85.92
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.68
    rCSI 2.16%
    PRS 66.34
  • alveolar adventitial fibroblast CL4028006
    CSI 1.6
    rCSI 2.53%
    PRS 83.85
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.59
    rCSI 3.45%
    PRS 70
  • mesothelial cell CL0000077
    CSI 1.54
    rCSI 6.02%
    PRS 61.58
  • epithelial cell of proximal tubule CL0002306
    CSI 1.46
    rCSI 3.57%
    PRS 74.92
  • alveolar macrophage CL0000583
    CSI 1.46
    rCSI 2.41%
    PRS 85.93
  • erythroid progenitor cell CL0000038
    CSI 1.46
    rCSI 8.37%
    PRS 86.88
  • thymocyte CL0000893
    CSI 1.4
    rCSI 4.96%
    PRS 96.8
  • forebrain radial glial cell CL0013000
    CSI 1.36
    rCSI 4.35%
    PRS 83.64
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.35
    rCSI 2.38%
    PRS 64.69
  • parietal epithelial cell CL1000452
    CSI 1.23
    rCSI 3.28%
    PRS 74.7
  • centrilobular region hepatocyte CL0019029
    CSI 1.22
    rCSI 3.18%
    PRS 80.64
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.21
    rCSI 3.99%
    PRS 68.43
  • germinal center B cell CL0000844
    CSI 1.21
    rCSI 3.61%
    PRS 90.52
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.16
    rCSI 2.82%
    PRS 63.1
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.15
    rCSI 2.92%
    PRS 73.3
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.09
    rCSI 2.82%
    PRS 78.06
  • club cell CL0000158
    CSI 1.03
    rCSI 1.5%
    PRS 77.27
  • epithelial cell of nephron CL1000449
    CSI 1
    rCSI 9.49%
    PRS 95.85
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.99
    rCSI 2.26%
    PRS 75.98
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.88
    rCSI 4.57%
    PRS 94.43
  • deuterosomal cell CL4033044
    CSI 0.81
    rCSI 2.75%
    PRS 79.13
  • blood vessel smooth muscle cell CL0019018
    CSI 0.77
    rCSI 6.25%
    PRS 77.15
  • podocyte CL0000653
    CSI 0.74
    rCSI 3.28%
    PRS 83
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 0.73
    rCSI 2.83%
    PRS 94.84
  • mesenchymal cell CL0008019
    CSI 0.71
    rCSI 1.82%
    PRS 76.24
  • eosinophil CL0000771
    CSI 0.61
    rCSI 4%
    PRS 95.2
  • pluripotent stem cell CL0002248
    CSI 0.57
    rCSI 17.02%
    PRS 91.22
  • pre-conventional dendritic cell CL0002010
    CSI 0.3
    rCSI 3.5%
    PRS 95.3%
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.4
    rCSI 3.8%
    PRS 78.5%
  • pluripotent stem cell CL0002248
    CSI 0.6
    rCSI 17.0%
    PRS 91.2%
  • eosinophil CL0000771
    CSI 0.6
    rCSI 4.0%
    PRS 95.2%
  • mesenchymal cell CL0008019
    CSI 0.7
    rCSI 1.8%
    PRS 76.2%
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 0.7
    rCSI 2.8%
    PRS 94.8%
  • podocyte CL0000653
    CSI 0.7
    rCSI 3.3%
    PRS 83.0%
  • blood vessel smooth muscle cell CL0019018
    CSI 0.8
    rCSI 6.3%
    PRS 77.2%
  • deuterosomal cell CL4033044
    CSI 0.8
    rCSI 2.8%
    PRS 79.1%
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.9
    rCSI 4.6%
    PRS 94.4%
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.0
    rCSI 2.3%
    PRS 76.0%
  • epithelial cell of nephron CL1000449
    CSI 1.0
    rCSI 9.5%
    PRS 95.9%
  • club cell CL0000158
    CSI 1.0
    rCSI 1.5%
    PRS 77.3%
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.1
    rCSI 2.8%
    PRS 78.1%
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.2
    rCSI 2.9%
    PRS 73.3%
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.2
    rCSI 2.8%
    PRS 63.1%
  • germinal center B cell CL0000844
    CSI 1.2
    rCSI 3.6%
    PRS 90.5%
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 1.2
    rCSI 4.0%
    PRS 68.4%
  • centrilobular region hepatocyte CL0019029
    CSI 1.2
    rCSI 3.2%
    PRS 80.6%
  • parietal epithelial cell CL1000452
    CSI 1.2
    rCSI 3.3%
    PRS 74.7%
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.4
    rCSI 2.4%
    PRS 64.7%
  • forebrain radial glial cell CL0013000
    CSI 1.4
    rCSI 4.4%
    PRS 83.6%
  • thymocyte CL0000893
    CSI 1.4
    rCSI 5.0%
    PRS 96.8%
  • erythroid progenitor cell CL0000038
    CSI 1.5
    rCSI 8.4%
    PRS 86.9%
  • alveolar macrophage CL0000583
    CSI 1.5
    rCSI 2.4%
    PRS 85.9%
  • epithelial cell of proximal tubule CL0002306
    CSI 1.5
    rCSI 3.6%
    PRS 74.9%
  • mesothelial cell CL0000077
    CSI 1.5
    rCSI 6.0%
    PRS 61.6%
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.6
    rCSI 3.5%
    PRS 70.0%
  • alveolar adventitial fibroblast CL4028006
    CSI 1.6
    rCSI 2.5%
    PRS 83.9%
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.7
    rCSI 2.2%
    PRS 66.3%
  • respiratory basal cell CL0002633
    CSI 1.8
    rCSI 1.8%
    PRS 85.9%
  • renal principal cell CL0005009
    CSI 1.8
    rCSI 4.7%
    PRS 82.6%
  • common lymphoid progenitor CL0000051
    CSI 1.8
    rCSI 2.4%
    PRS 94.7%
  • fibroblast CL0000057
    CSI 1.9
    rCSI 5.3%
    PRS 76.3%
  • Schwann cell CL0002573
    CSI 1.9
    rCSI 5.3%
    PRS 78.1%
  • chondrocyte CL0000138
    CSI 1.9
    rCSI 3.0%
    PRS 75.9%
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.0
    rCSI 17.5%
    PRS 76.8%
  • hepatocyte CL0000182
    CSI 2.1
    rCSI 3.8%
    PRS 81.7%
  • mesodermal cell CL0000222
    CSI 2.1
    rCSI 2.5%
    PRS 80.6%
  • direct pathway medium spiny neuron CL4023026
    CSI 2.1
    rCSI 51.1%
    PRS 63.2%
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.2
    rCSI 2.2%
    PRS 90.8%
  • adipocyte CL0000136
    CSI 2.2
    rCSI 2.8%
    PRS 72.9%
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.2
    rCSI 53.4%
    PRS 63.7%
  • erythroid lineage cell CL0000764
    CSI 2.2
    rCSI 14.3%
    PRS 89.8%
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 2.3
    rCSI 6.9%
    PRS 86.2%
  • placental villous trophoblast CL2000060
    CSI 2.5
    rCSI 3.9%
    PRS 81.5%
  • elicited macrophage CL0000861
    CSI 2.5
    rCSI 2.3%
    PRS 89.4%
  • promonocyte CL0000559
    CSI 2.6
    rCSI 4.4%
    PRS 87.6%
  • inhibitory interneuron CL0000498
    CSI 2.7
    rCSI 6.1%
    PRS 70.8%
  • Kupffer cell CL0000091
    CSI 2.8
    rCSI 6.4%
    PRS 83.2%
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.9
    rCSI 6.9%
    PRS 69.5%
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.9
    rCSI 3.7%
    PRS 78.6%
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.0
    rCSI 2.1%
    PRS 85.9%
  • stem cell CL0000034
    CSI 3.0
    rCSI 2.9%
    PRS 76.5%
  • bronchus fibroblast of lung CL2000093
    CSI 3.2
    rCSI 2.6%
    PRS 81.9%
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.3
    rCSI 3.9%
    PRS 65.3%
  • epithelial cell of lung CL0000082
    CSI 3.3
    rCSI 2.7%
    PRS 83.4%
  • mature astrocyte CL0002627
    CSI 3.3
    rCSI 14.1%
    PRS 75.0%
  • periportal region hepatocyte CL0019026
    CSI 3.3
    rCSI 13.0%
    PRS 81.5%
  • granulocyte monocyte progenitor cell CL0000557
    CSI 3.4
    rCSI 2.9%
    PRS 86.2%
  • promyelocyte CL0000836
    CSI 3.4
    rCSI 4.9%
    PRS 87.5%
  • midzonal region hepatocyte CL0019028
    CSI 3.4
    rCSI 8.1%
    PRS 82.1%
  • intestinal epithelial cell CL0002563
    CSI 3.5
    rCSI 3.7%
    PRS 80.1%
  • cerebral cortex neuron CL0010012
    CSI 3.7
    rCSI 15.0%
    PRS 74.3%
  • fraction A pre-pro B cell CL0002045
    CSI 3.7
    rCSI 4.2%
    PRS 91.3%
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.7
    rCSI 4.6%
    PRS 63.1%
  • glioblast CL0000030
    CSI 3.9
    rCSI 6.2%
    PRS 74.1%
  • multi-ciliated epithelial cell CL0005012
    CSI 4.0
    rCSI 4.0%
    PRS 76.5%
  • early lymphoid progenitor CL0000936
    CSI 4.0
    rCSI 3.5%
    PRS 87.2%
  • pericyte CL0000669
    CSI 4.5
    rCSI 12.0%
    PRS 60.5%
  • transit amplifying cell CL0009010
    CSI 4.6
    rCSI 7.0%
    PRS 89.5%
  • endocardial cell CL0002350
    CSI 4.8
    rCSI 22.9%
    PRS 78.8%
  • endothelial cell of placenta CL0009092
    CSI 4.8
    rCSI 23.7%
    PRS 89.0%
  • colon epithelial cell CL0011108
    CSI 5.1
    rCSI 5.3%
    PRS 79.9%
  • plasmablast CL0000980
    CSI 5.3
    rCSI 4.1%
    PRS 86.9%
  • erythroblast CL0000765
    CSI 5.3
    rCSI 14.1%
    PRS 87.0%
  • common dendritic progenitor CL0001029
    CSI 5.5
    rCSI 6.9%
    PRS 89.9%
  • primitive red blood cell CL0002355
    CSI 5.7
    rCSI 30.9%
    PRS 87.6%
  • common myeloid progenitor CL0000049
    CSI 5.8
    rCSI 4.7%
    PRS 84.6%
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 6.1
    rCSI 7.0%
    PRS 74.7%
  • pro-B cell CL0000826
    CSI 6.2
    rCSI 5.1%
    PRS 84.5%
  • hepatic stellate cell CL0000632
    CSI 6.3
    rCSI 23.6%
    PRS 75.3%
  • cardiac blood vessel endothelial cell CL0010006
    CSI 6.5
    rCSI 46.2%
    PRS 75.5%
  • transit amplifying cell of colon CL0009011
    CSI 6.5
    rCSI 7.7%
    PRS 83.9%
  • transit amplifying cell of small intestine CL0009012
    CSI 6.8
    rCSI 30.0%
    PRS 89.2%
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 7.0
    rCSI 6.3%
    PRS 80.8%
  • neural crest cell CL0011012
    CSI 8.2
    rCSI 6.5%
    PRS 72.1%
  • radial glial cell CL0000681
    CSI 8.5
    rCSI 11.8%
    PRS 80.8%
  • goblet cell CL0000160
    CSI 9.0
    rCSI 8.5%
    PRS 80.9%
  • perivascular cell CL4033054
    CSI 9.0
    rCSI 12.4%
    PRS 86.7%
  • extravillous trophoblast CL0008036
    CSI 9.2
    rCSI 11.4%
    PRS 80.6%
  • interstitial cell of Cajal CL0002088
    CSI 9.7
    rCSI 12.3%
    PRS 87.2%
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 9.8
    rCSI 11.8%
    PRS 89.2%
  • erythrocyte CL0000232
    CSI 10.0
    rCSI 22.7%
    PRS 82.6%
  • choroid plexus epithelial cell CL0000706
    CSI 11.0
    rCSI 18.0%
    PRS 72.4%
  • intestine goblet cell CL0019031
    CSI 11.1
    rCSI 9.8%
    PRS 80.3%
  • Hofbauer cell CL3000001
    CSI 11.5
    rCSI 21.8%
    PRS 89.4%
  • large pre-B-II cell CL0000957
    CSI 12.7
    rCSI 36.4%
    PRS 86.8%
  • blood vessel endothelial cell CL0000071
    CSI 13.0
    rCSI 26.9%
    PRS 79.4%
  • fallopian tube secretory epithelial cell CL4030006
    CSI 13.8
    rCSI 13.3%
    PRS 81.9%

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.

Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Dihydrofolate reductase ([DHFR](/details-gene/1719)) is a crucial enzyme that catalyzes the conversion of dihydrofolate to tetrahydrofolate, an essential cofactor for the synthesis of purines, thymidylate, and several amino acids. This function places [DHFR](/details-gene/1719) at the heart of one-carbon metabolism and links it directly to DNA synthesis and cell proliferation, as highlighted by its association with the `Cell cycle` pathway ([R-HSA-1640170](https://reactome.org/content/detail/R-HSA-1640170)). Its clinical significance is underscored by its role as the primary target for the antifolate drug methotrexate and its genetic association with dihydrofolate reductase deficiency ([126060](https://omim.org/entry/126060)). **Overall**, expression data reveals high significance in rapidly dividing cells such as `[precursor B cell](/details-cell/CL0000817)` as well as in metabolically active, terminally differentiated cells like `[cardiac muscle cell](/details-cell/CL0000746)`, suggesting its functions extend beyond proliferation to include general metabolic maintenance. ## Cellular Roles and Expression Landscape The expression profile of [DHFR](/details-gene/1719) indicates its fundamental importance in highly proliferative and biosynthetically active cell types. The highest significance is observed in hematopoietic progenitors, including `[precursor B cell](/details-cell/CL0000817)` (CSI: 33.67) and `[large pre-B-II cell](/details-cell/CL0000957)` (CSI: 12.73), which is consistent with its canonical role in providing the nucleotide precursors required for rapid cell division. Beyond hematopoietic cells, [DHFR](/details-gene/1719) shows prominent significance in tissues with high metabolic or secretory demands. Its high CSI in `[cardiac muscle cell](/details-cell/CL0000746)` (CSI: 29.87) suggests a critical role in maintaining the metabolic integrity of cardiomyocytes, possibly unrelated to cell division. Similarly, its expression in secretory cells like `[fallopian tube secretory epithelial cell](/details-cell/CL4030006)` and `[intestine goblet cell](/details-cell/CL0019031)`, as well as in `[blood vessel endothelial cell](/details-cell/CL0000071)`, points to a widespread requirement for folate pathway activity in cellular maintenance, repair, and function across diverse lineages. The gene's activity in specialized placental cells, such as `[Hofbauer cell](/details-cell/CL3000001)` and `[extravillous trophoblast](/details-cell/CL0008036)`, further highlights its necessity during development and tissue remodeling. ## Pathways and Molecular Function The primary molecular function of [DHFR](/details-gene/1719) is its `Dihydrofolate reductase activity` ([GO:0004146](https://www.ebi.ac.uk/QuickGO/term/GO:0004146)), which is central to the `Metabolism of folate and pterines` ([R-HSA-196757](https://reactome.org/content/detail/R-HSA-196757)). This activity is indispensable for the `Tetrahydrofolate biosynthetic process` ([GO:0046654](https://www.ebi.ac.uk/QuickGO/term/GO:0046654)), producing a cofactor essential for the `One-carbon metabolic process` ([GO:0006730](https://www.ebi.ac.uk/QuickGO/term/GO:0006730)) that fuels nucleotide synthesis. This direct link to DNA replication machinery explains its deep integration with the `G1/s transition` phase of the cell cycle ([R-HSA-69206](https://reactome.org/content/detail/R-HSA-69206)). Interestingly, functional annotations suggest a non-canonical, or "moonlighting," role for [DHFR](/details-gene/1719). Its annotation for `Mrna binding` ([GO:0003729](https://www.ebi.ac.uk/QuickGO/term/GO:0003729)) and `Mrna regulatory element binding translation repressor activity` ([GO:0000900](https://www.ebi.ac.uk/QuickGO/term/GO:0000900)) suggests it may directly regulate gene expression at the translational level, potentially by binding its own mRNA to autoregulate its synthesis. Its presence in both the `Cytosol` ([GO:0005829](https://www.ebi.ac.uk/QuickGO/term/GO:0005829)) and `Mitochondrion` ([GO:0005739](https://www.ebi.ac.uk/QuickGO/term/GO:0005739)) aligns with evidence of distinct folate metabolism pathways in these compartments, including a mitochondrial pathway for thymidylate biosynthesis ([Link](https://doi.org/10.1073/pnas.1103623108)). Furthermore, its role in the `Response to methotrexate` ([GO:0031427](https://www.ebi.ac.uk/QuickGO/term/GO:0031427)) solidifies its status as a key pharmacological target. ## Research Directions The data highlights both canonical and non-canonical functions of [DHFR](/details-gene/1719), opening several avenues for future investigation. While its role in proliferation is well-established, its high significance in terminally differentiated cells and its potential regulatory functions warrant deeper exploration. Based on the available data, several testable hypotheses can be proposed: 1. In terminally differentiated cells like `[cardiac muscle cell](/details-cell/CL0000746)`, the high expression of [DHFR](/details-gene/1719) is not primarily for nucleotide synthesis but is essential for maintaining redox homeostasis and mitochondrial integrity through its contribution to tetrahydrobiopterin (BH4) biosynthesis ([R-HSA-1474151](https://reactome.org/content/detail/R-HSA-1474151)) and the regulation of superoxide radicals ([GO:2000121](https://www.ebi.ac.uk/QuickGO/term/GO:2000121)). 2. [DHFR](/details-gene/1719) functions as a moonlighting protein that directly represses the translation of its own mRNA as a feedback mechanism. This binding affinity may be allosterically regulated by the intracellular concentrations of its substrates (dihydrofolate) and products (tetrahydrofolate), thereby fine-tuning nucleotide availability. A compelling experiment to test the second hypothesis would be to investigate its role as a translational repressor. * **Suggested Experiment:** To validate that [DHFR](/details-gene/1719) binds its own mRNA, one could perform RNA-immunoprecipitation followed by qPCR (RIP-qPCR) using a DHFR-specific antibody in a cell line with high expression, such as a B-lymphoblastoid line. To test the functional consequence, polysome profiling could be conducted on cells under normal conditions versus cells treated with methotrexate. If [DHFR](/details-gene/1719) is a translational repressor, inhibition with methotrexate should trap the protein on its target mRNA, leading to a shift of the DHFR mRNA transcript away from heavy polysomes (active translation) and toward lighter polysomes or monosomes (repressed translation). From a therapeutic standpoint, [DHFR](/details-gene/1719) is a classic example of a successful drug target. Its **inhibition** by methotrexate and other antifolates is a cornerstone of chemotherapy and treatment for autoimmune disorders. The potential for non-canonical functions, however, suggests new therapeutic possibilities. If its mRNA-binding activity is confirmed to regulate specific cellular programs, it may be possible to design small molecules that modulate this interaction specifically, potentially offering a new class of therapeutics with a different mechanism of action and side-effect profile compared to classic enzymatic inhibitors.

Genular Protein ID: 4053884756

Symbol: DYR_HUMAN

Name: Dihydrofolate reductase

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 6323448

Title: The functional human dihydrofolate reductase gene.

PubMed ID: 6323448

DOI: 10.1016/s0021-9258(17)43186-3

PubMed ID: 6687716

Title: The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase.

PubMed ID: 6687716

DOI: 10.1016/0378-1119(83)90147-6

PubMed ID: 6235374

Title: Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes.

PubMed ID: 6235374

DOI: 10.1016/0022-2836(84)90419-4

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21310276

Title: Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.

PubMed ID: 21310276

DOI: 10.1016/j.ajhg.2011.01.004

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21876184

Title: The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional.

PubMed ID: 21876184

DOI: 10.1073/pnas.1103605108

PubMed ID: 21876188

Title: Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria.

PubMed ID: 21876188

DOI: 10.1073/pnas.1103623108

PubMed ID: 3383852

Title: Crystal structure of human dihydrofolate reductase complexed with folate.

PubMed ID: 3383852

DOI: 10.1111/j.1432-1033.1988.tb14108.x

PubMed ID: 2248959

Title: Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate.

PubMed ID: 2248959

DOI: 10.1021/bi00492a021

PubMed ID: 1731871

Title: Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution.

PubMed ID: 1731871

DOI: 10.1021/bi00116a031

PubMed ID: 7890613

Title: Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22. Kinetics, crystallography, and potential as selectable markers.

PubMed ID: 7890613

DOI: 10.1074/jbc.270.10.5057

PubMed ID: 9374868

Title: 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

DOI: 10.1021/bi971711l

PubMed ID: 9719595

Title: Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents.

PubMed ID: 9719595

DOI: 10.1021/jm980081y

PubMed ID: 12096917

Title: Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 A and 1.05 A resolution.

PubMed ID: 12096917

DOI: 10.1016/s0022-2836(02)00469-2

PubMed ID: 12657784

Title: Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductase.

PubMed ID: 12657784

DOI: 10.1107/s0907444903001951

PubMed ID: 12925791

Title: Analysis of three crystal structure determinations of a 5-methyl-6-N-methylanilino pyridopyrimidine antifolate complex with human dihydrofolate reductase.

PubMed ID: 12925791

DOI: 10.1107/s0907444903014963

PubMed ID: 15039552

Title: Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry.

PubMed ID: 15039552

DOI: 10.1107/s0907444904002094

PubMed ID: 15681865

Title: Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH.

PubMed ID: 15681865

DOI: 10.1107/s0907444904030422

PubMed ID: 16222560

Title: Solution structure of human dihydrofolate reductase in its complex with trimethoprim and NADPH.

PubMed ID: 16222560

DOI: 10.1007/s10858-005-1475-z

PubMed ID: 17569517

Title: Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation.

PubMed ID: 17569517

DOI: 10.1021/jm0701977

PubMed ID: 19196009

Title: Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes.

PubMed ID: 19196009

DOI: 10.1021/bi801960h

PubMed ID: 19478082

Title: Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E double mutant suggest structural basis for methotrexate resistance.

PubMed ID: 19478082

DOI: 10.1074/jbc.m109.018010

PubMed ID: 19719239

Title: Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents.

PubMed ID: 19719239

DOI: 10.1021/jm900490a

PubMed ID: 21310277

Title: Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

PubMed ID: 21310277

DOI: 10.1016/j.ajhg.2011.01.007

Sequence Information:

  • Length: 187
  • Mass: 21453
  • Checksum: EBDF3D1EC73E1566
  • Sequence:
  • MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 
    IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 
    VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 
    EVYEKND

Genular Protein ID: 3716210371

Symbol: B4DM58_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

Sequence Information:

  • Length: 129
  • Mass: 14500
  • Checksum: A86D545B3347CB61
  • Sequence:
  • MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 
    IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 
    VYKIPRCSL