Details for: MAP3K4

Gene ID: 4216

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: MAP3K4

Ensembl ID: ENSG00000085511

Description: mitogen-activated protein kinase kinase kinase 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • L6b glutamatergic cortical neuron CL4023038
    CSI 18.38
    rCSI 57.45%
    PRS 45.83
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 14.89
    rCSI 36.19%
    PRS 42.79
  • enteroendocrine cell CL0000164
    CSI 12.35
    rCSI 16.88%
    PRS 64.26
  • lung ciliated cell CL1000271
    CSI 11.92
    rCSI 13.79%
    PRS 52.7
  • IgA plasma cell CL0000987
    CSI 11.77
    rCSI 12.05%
    PRS 76.68
  • erythroblast CL0000765
    CSI 11.34
    rCSI 30.09%
    PRS 73.7
  • plasmablast CL0000980
    CSI 11.06
    rCSI 8.7%
    PRS 69.33
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 10.43
    rCSI 32.61%
    PRS 48.3
  • myoepithelial cell CL0000185
    CSI 9.53
    rCSI 24.11%
    PRS 70.49
  • T-helper 17 cell CL0000899
    CSI 8.91
    rCSI 7.08%
    PRS 83.61
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 8.87
    rCSI 52.23%
    PRS 45.39
  • alveolar adventitial fibroblast CL4028006
    CSI 8.69
    rCSI 13.73%
    PRS 64.78
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 8.12
    rCSI 29.22%
    PRS 42.56
  • retinal ganglion cell CL0000740
    CSI 7.18
    rCSI 15.87%
    PRS 48.63
  • common dendritic progenitor CL0001029
    CSI 7.17
    rCSI 9%
    PRS 72.98
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 6.53
    rCSI 3.85%
    PRS 79.9
  • type B pancreatic cell CL0000169
    CSI 6.5
    rCSI 14.4%
    PRS 60.55
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 6.08
    rCSI 10.21%
    PRS 44.17
  • radial glial cell CL0000681
    CSI 5.74
    rCSI 7.97%
    PRS 61.09
  • melanocyte CL0000148
    CSI 5.31
    rCSI 3.93%
    PRS 55.01
  • central nervous system neuron CL2000029
    CSI 5.23
    rCSI 38.47%
    PRS 48.99
  • parietal epithelial cell CL1000452
    CSI 5.08
    rCSI 13.56%
    PRS 53.41
  • naive T cell CL0000898
    CSI 4.95
    rCSI 3.45%
    PRS 77.74
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.91
    rCSI 12.46%
    PRS 51.96
  • CD14-positive monocyte CL0001054
    CSI 4.89
    rCSI 6.09%
    PRS 73.39
  • neuroendocrine cell CL0000165
    CSI 4.87
    rCSI 18.85%
    PRS 76.79
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 4.63
    rCSI 3.12%
    PRS 75.79
  • mucosal invariant T cell CL0000940
    CSI 4.27
    rCSI 3.45%
    PRS 72.87
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 4.19
    rCSI 5.22%
    PRS 42.27
  • mature T cell CL0002419
    CSI 4.12
    rCSI 3.21%
    PRS 80.21
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 4
    rCSI 2.87%
    PRS 76.76
  • pro-B cell CL0000826
    CSI 3.95
    rCSI 3.27%
    PRS 64.75
  • CD4-positive helper T cell CL0000492
    CSI 3.9
    rCSI 2.95%
    PRS 76.49
  • bronchus fibroblast of lung CL2000093
    CSI 3.81
    rCSI 3.1%
    PRS 62.98
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.79
    rCSI 23.7%
    PRS 54.16
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.79
    rCSI 6.09%
    PRS 46.17
  • cerebellar neuron CL1001611
    CSI 3.72
    rCSI 32.74%
    PRS 49.54
  • promonocyte CL0000559
    CSI 3.55
    rCSI 6.08%
    PRS 71.42
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 3.53
    rCSI 8.06%
    PRS 58.88
  • cerebellar granule cell CL0001031
    CSI 3.48
    rCSI 5.12%
    PRS 55.9
  • retinal bipolar neuron CL0000748
    CSI 3.43
    rCSI 6.43%
    PRS 50.74
  • type EC enteroendocrine cell CL0000577
    CSI 3.4
    rCSI 12.09%
    PRS 71.11
  • inhibitory interneuron CL0000498
    CSI 3.33
    rCSI 7.7%
    PRS 51.52
  • choroid plexus epithelial cell CL0000706
    CSI 3.33
    rCSI 5.46%
    PRS 51.69
  • alpha-beta T cell CL0000789
    CSI 3.33
    rCSI 3.9%
    PRS 78.98
  • pulmonary alveolar type 1 cell CL0002062
    CSI 3.31
    rCSI 19.07%
    PRS 60.91
  • stromal cell CL0000499
    CSI 3.29
    rCSI 9.25%
    PRS 59.13
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 3.2
    rCSI 3.7%
    PRS 55.59
  • pancreatic A cell CL0000171
    CSI 3.17
    rCSI 3.32%
    PRS 66.18
  • neural crest cell CL0011012
    CSI 3.15
    rCSI 2.49%
    PRS 49.35
  • double negative thymocyte CL0002489
    CSI 3.15
    rCSI 2.19%
    PRS 73.83
  • unswitched memory B cell CL0000970
    CSI 3.12
    rCSI 2.62%
    PRS 79.51
  • common myeloid progenitor CL0000049
    CSI 3.1
    rCSI 2.51%
    PRS 63.96
  • vascular leptomeningeal cell CL4023051
    CSI 3.08
    rCSI 5.4%
    PRS 54.31
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.06
    rCSI 2.76%
    PRS 59.45
  • T follicular helper cell CL0002038
    CSI 2.98
    rCSI 2.23%
    PRS 77.87
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 2.98
    rCSI 2.26%
    PRS 75.68
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.97
    rCSI 8.01%
    PRS 69.55
  • mesodermal cell CL0000222
    CSI 2.94
    rCSI 3.53%
    PRS 60.66
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.86
    rCSI 4.05%
    PRS 58.77
  • Mueller cell CL0000636
    CSI 2.81
    rCSI 6.42%
    PRS 54.18
  • precursor B cell CL0000817
    CSI 2.79
    rCSI 2.44%
    PRS 72.04
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.78
    rCSI 3.58%
    PRS 45.49
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.69
    rCSI 4.76%
    PRS 43.24
  • cardiac endothelial cell CL0010008
    CSI 2.67
    rCSI 10.77%
    PRS 61.19
  • glioblast CL0000030
    CSI 2.65
    rCSI 4.23%
    PRS 55.02
  • interneuron CL0000099
    CSI 2.62
    rCSI 5.27%
    PRS 51.55
  • intestinal tuft cell CL0019032
    CSI 2.62
    rCSI 4%
    PRS 66.77
  • pancreatic D cell CL0000173
    CSI 2.5
    rCSI 2.46%
    PRS 65.22
  • direct pathway medium spiny neuron CL4023026
    CSI 2.4
    rCSI 57.58%
    PRS 43.17
  • activated type II NK T cell CL0000931
    CSI 2.4
    rCSI 2.7%
    PRS 78.77
  • mesothelial cell CL0000077
    CSI 2.4
    rCSI 9.37%
    PRS 39.06
  • hepatocyte CL0000182
    CSI 2.36
    rCSI 4.22%
    PRS 61.56
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.35
    rCSI 2.03%
    PRS 67.58
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.34
    rCSI 1.82%
    PRS 64.55
  • fibroblast of lung CL0002553
    CSI 2.33
    rCSI 2.17%
    PRS 63.08
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.32
    rCSI 3.71%
    PRS 66.66
  • fibroblast of cardiac tissue CL0002548
    CSI 2.3
    rCSI 11.02%
    PRS 62.4
  • ependymal cell CL0000065
    CSI 2.3
    rCSI 4.67%
    PRS 41.74
  • OFF midget ganglion cell CL4033047
    CSI 2.3
    rCSI 46.78%
    PRS 54.58
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.29
    rCSI 55.28%
    PRS 44.01
  • ON midget ganglion cell CL4033046
    CSI 2.25
    rCSI 45.91%
    PRS 53.2
  • ciliated cell CL0000064
    CSI 2.24
    rCSI 3.63%
    PRS 59.16
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.22
    rCSI 8.4%
    PRS 44.9
  • conjunctival epithelial cell CL1000432
    CSI 2.21
    rCSI 3.38%
    PRS 63.18
  • Kupffer cell CL0000091
    CSI 2.18
    rCSI 4.98%
    PRS 62.4
  • alveolar macrophage CL0000583
    CSI 2.18
    rCSI 3.58%
    PRS 67.74
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.17
    rCSI 2.38%
    PRS 66.29
  • nasal mucosa goblet cell CL0002480
    CSI 2.16
    rCSI 2.51%
    PRS 70.11
  • blood vessel endothelial cell CL0000071
    CSI 2.15
    rCSI 4.47%
    PRS 59.64
  • secretory cell CL0000151
    CSI 2.1
    rCSI 2.19%
    PRS 62.83
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.08
    rCSI 4.66%
    PRS 44.9
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.07
    rCSI 3.76%
    PRS 54.23
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.05
    rCSI 5.35%
    PRS 62.22
  • hepatic stellate cell CL0000632
    CSI 2.05
    rCSI 7.67%
    PRS 54.41
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.02
    rCSI 1.87%
    PRS 81.79
  • ciliated epithelial cell CL0000067
    CSI 2.01
    rCSI 1.77%
    PRS 50.44
  • small intestine goblet cell CL1000495
    CSI 1.98
    rCSI 4.33%
    PRS 70.48
  • glycinergic amacrine cell CL4030028
    CSI 1.96
    rCSI 5.1%
    PRS 59.86
  • retinal rod cell CL0000604
    CSI 1.95
    rCSI 3.44%
    PRS 59.32
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.2
    rCSI 1.7%
    PRS 60.6%
  • medium spiny neuron CL1001474
    CSI 0.3
    rCSI 2.8%
    PRS 49.7%
  • endothelial cell of placenta CL0009092
    CSI 0.4
    rCSI 1.8%
    PRS 73.5%
  • H2 horizontal cell CL0004218
    CSI 0.5
    rCSI 2.5%
    PRS 59.7%
  • starburst amacrine cell CL0004232
    CSI 0.6
    rCSI 5.0%
    PRS 53.9%
  • dopaminergic neuron CL0000700
    CSI 0.6
    rCSI 3.4%
    PRS 47.6%
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.6
    rCSI 3.3%
    PRS 77.9%
  • GABAergic amacrine cell CL4030027
    CSI 0.7
    rCSI 2.3%
    PRS 51.2%
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.7
    rCSI 2.2%
    PRS 49.4%
  • ON parasol ganglion cell CL4033052
    CSI 0.7
    rCSI 9.7%
    PRS 53.4%
  • glial cell CL0000125
    CSI 0.8
    rCSI 3.1%
    PRS 53.2%
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.9
    rCSI 2.1%
    PRS 49.7%
  • blood vessel smooth muscle cell CL0019018
    CSI 0.9
    rCSI 7.3%
    PRS 55.7%
  • regular atrial cardiac myocyte CL0002129
    CSI 0.9
    rCSI 2.9%
    PRS 60.5%
  • placental villous trophoblast CL2000060
    CSI 0.9
    rCSI 1.4%
    PRS 60.8%
  • H1 horizontal cell CL0004217
    CSI 0.9
    rCSI 3.7%
    PRS 61.5%
  • glutamatergic neuron CL0000679
    CSI 0.9
    rCSI 1.9%
    PRS 52.7%
  • intermediate monocyte CL0002393
    CSI 1.0
    rCSI 1.5%
    PRS 66.8%
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.0
    rCSI 0.8%
    PRS 63.1%
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.0
    rCSI 2.9%
    PRS 82.3%
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.0
    rCSI 1.2%
    PRS 71.5%
  • BEST4+ enteroycte CL4030026
    CSI 1.0
    rCSI 1.3%
    PRS 64.2%
  • myeloid dendritic cell CL0000782
    CSI 1.1
    rCSI 1.5%
    PRS 78.4%
  • renal interstitial pericyte CL1001318
    CSI 1.1
    rCSI 3.0%
    PRS 58.0%
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.1
    rCSI 5.4%
    PRS 75.2%
  • tracheobronchial smooth muscle cell CL0019019
    CSI 1.1
    rCSI 2.0%
    PRS 70.7%
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.2
    rCSI 2.5%
    PRS 75.0%
  • amacrine cell CL0000561
    CSI 1.2
    rCSI 3.5%
    PRS 52.1%
  • Bergmann glial cell CL0000644
    CSI 1.2
    rCSI 1.7%
    PRS 55.8%
  • keratinocyte CL0000312
    CSI 1.2
    rCSI 1.0%
    PRS 66.9%
  • squamous epithelial cell CL0000076
    CSI 1.2
    rCSI 2.9%
    PRS 66.2%
  • renal principal cell CL0005009
    CSI 1.2
    rCSI 3.2%
    PRS 66.0%
  • retina horizontal cell CL0000745
    CSI 1.3
    rCSI 1.9%
    PRS 58.8%
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 1.3
    rCSI 2.8%
    PRS 50.2%
  • GABAergic neuron CL0000617
    CSI 1.3
    rCSI 4.3%
    PRS 47.6%
  • acinar cell CL0000622
    CSI 1.3
    rCSI 1.9%
    PRS 74.2%
  • keratocyte CL0002363
    CSI 1.4
    rCSI 3.3%
    PRS 69.8%
  • cardiac muscle cell CL0000746
    CSI 1.4
    rCSI 2.0%
    PRS 52.0%
  • retinal pigment epithelial cell CL0002586
    CSI 1.4
    rCSI 2.8%
    PRS 60.2%
  • rod bipolar cell CL0000751
    CSI 1.4
    rCSI 2.5%
    PRS 55.6%
  • helper T cell CL0000912
    CSI 1.4
    rCSI 2.0%
    PRS 67.5%
  • extravillous trophoblast CL0008036
    CSI 1.4
    rCSI 1.8%
    PRS 59.2%
  • retinal cone cell CL0000573
    CSI 1.5
    rCSI 2.4%
    PRS 52.0%
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 1.5
    rCSI 3.6%
    PRS 80.1%
  • chondrocyte CL0000138
    CSI 1.5
    rCSI 2.4%
    PRS 54.9%
  • Schwann cell CL0002573
    CSI 1.5
    rCSI 4.4%
    PRS 60.4%
  • epithelial cell of proximal tubule CL0002306
    CSI 1.6
    rCSI 3.9%
    PRS 55.9%
  • neuron CL0000540
    CSI 1.6
    rCSI 4.3%
    PRS 51.6%
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.6
    rCSI 2.5%
    PRS 69.9%
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.6
    rCSI 6.4%
    PRS 82.3%
  • basal cell CL0000646
    CSI 1.6
    rCSI 2.2%
    PRS 62.9%
  • duct epithelial cell CL0000068
    CSI 1.6
    rCSI 2.4%
    PRS 67.4%
  • renal beta-intercalated cell CL0002201
    CSI 1.7
    rCSI 4.0%
    PRS 63.2%
  • elicited macrophage CL0000861
    CSI 1.7
    rCSI 1.5%
    PRS 71.4%
  • dendritic cell, human CL0001056
    CSI 1.7
    rCSI 2.6%
    PRS 71.6%
  • adipocyte CL0000136
    CSI 1.7
    rCSI 2.2%
    PRS 54.8%
  • multi-ciliated epithelial cell CL0005012
    CSI 1.7
    rCSI 1.7%
    PRS 55.9%
  • respiratory basal cell CL0002633
    CSI 1.8
    rCSI 1.8%
    PRS 68.3%
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.8
    rCSI 4.6%
    PRS 57.5%
  • cardiac neuron CL0010022
    CSI 1.8
    rCSI 5.6%
    PRS 59.5%
  • stem cell CL0000034
    CSI 1.8
    rCSI 1.8%
    PRS 53.2%
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 1.9
    rCSI 1.7%
    PRS 77.1%
  • intestinal epithelial cell CL0002563
    CSI 1.9
    rCSI 2.0%
    PRS 60.5%
  • lung secretory cell CL1000272
    CSI 1.9
    rCSI 4.7%
    PRS 61.0%
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.9
    rCSI 2.3%
    PRS 43.9%
  • cerebral cortex endothelial cell CL1001602
    CSI 1.9
    rCSI 3.3%
    PRS 52.6%
  • ionocyte CL0005006
    CSI 1.9
    rCSI 2.1%
    PRS 62.1%
  • group 3 innate lymphoid cell CL0001071
    CSI 1.9
    rCSI 1.5%
    PRS 68.1%
  • retinal rod cell CL0000604
    CSI 2.0
    rCSI 3.4%
    PRS 59.3%
  • glycinergic amacrine cell CL4030028
    CSI 2.0
    rCSI 5.1%
    PRS 59.9%
  • small intestine goblet cell CL1000495
    CSI 2.0
    rCSI 4.3%
    PRS 70.5%
  • ciliated epithelial cell CL0000067
    CSI 2.0
    rCSI 1.8%
    PRS 50.4%
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 2.0
    rCSI 1.9%
    PRS 81.8%
  • hepatic stellate cell CL0000632
    CSI 2.1
    rCSI 7.7%
    PRS 54.4%
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 2.1
    rCSI 5.4%
    PRS 62.2%
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.1
    rCSI 3.8%
    PRS 54.2%
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.1
    rCSI 4.7%
    PRS 44.9%
  • secretory cell CL0000151
    CSI 2.1
    rCSI 2.2%
    PRS 62.8%
  • blood vessel endothelial cell CL0000071
    CSI 2.2
    rCSI 4.5%
    PRS 59.6%
  • nasal mucosa goblet cell CL0002480
    CSI 2.2
    rCSI 2.5%
    PRS 70.1%
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.2
    rCSI 2.4%
    PRS 66.3%
  • alveolar macrophage CL0000583
    CSI 2.2
    rCSI 3.6%
    PRS 67.7%
  • Kupffer cell CL0000091
    CSI 2.2
    rCSI 5.0%
    PRS 62.4%
  • conjunctival epithelial cell CL1000432
    CSI 2.2
    rCSI 3.4%
    PRS 63.2%
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.2
    rCSI 8.4%
    PRS 44.9%
  • ciliated cell CL0000064
    CSI 2.2
    rCSI 3.6%
    PRS 59.2%
  • ON midget ganglion cell CL4033046
    CSI 2.3
    rCSI 45.9%
    PRS 53.2%
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.3
    rCSI 55.3%
    PRS 44.0%
  • OFF midget ganglion cell CL4033047
    CSI 2.3
    rCSI 46.8%
    PRS 54.6%
  • ependymal cell CL0000065
    CSI 2.3
    rCSI 4.7%
    PRS 41.7%
  • fibroblast of cardiac tissue CL0002548
    CSI 2.3
    rCSI 11.0%
    PRS 62.4%
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.3
    rCSI 3.7%
    PRS 66.7%
  • fibroblast of lung CL0002553
    CSI 2.3
    rCSI 2.2%
    PRS 63.1%
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.3
    rCSI 1.8%
    PRS 64.6%
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.4
    rCSI 2.0%
    PRS 67.6%
  • hepatocyte CL0000182
    CSI 2.4
    rCSI 4.2%
    PRS 61.6%
  • mesothelial cell CL0000077
    CSI 2.4
    rCSI 9.4%
    PRS 39.1%
  • activated type II NK T cell CL0000931
    CSI 2.4
    rCSI 2.7%
    PRS 78.8%
  • direct pathway medium spiny neuron CL4023026
    CSI 2.4
    rCSI 57.6%
    PRS 43.2%
  • pancreatic D cell CL0000173
    CSI 2.5
    rCSI 2.5%
    PRS 65.2%

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 [MAP3K4](/details-gene/4216) (mitogen-activated protein kinase kinase kinase 4) is a protein-coding gene located on chromosome 6q26 that encodes a member of the serine/threonine protein kinase family. As a MAP kinase kinase kinase (MAP3K), it functions as an apical component of intracellular signaling cascades, primarily activating the p38 and JNK MAP kinase pathways in response to cellular stress and cytokines [Link](https://doi.org/10.1093/emboj/16.16.4973). **Overall**, expression data indicate that [MAP3K4](/details-gene/4216) is a significant gene across a wide range of functionally diverse cell types, with particularly high significance in various neuronal subtypes, including [L6b glutamatergic cortical neurons](/details-cell/CL4023038) and [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040), as well as in secretory cells like [enteroendocrine cells](/details-cell/CL0000164) and hematopoietic lineages such as [IgA plasma cells](/details-cell/CL0000987). This broad expression pattern underscores its fundamental role in signal transduction across different physiological systems. ## Cellular Roles and Expression Landscape The expression profile of [MAP3K4](/details-gene/4216) suggests a critical role in multiple, distinct biological systems, most notably the central nervous system and the hematopoietic system. **Overall**, the gene shows the highest significance in several glutamatergic neuron subtypes of the cerebral cortex, including [L6b glutamatergic cortical neurons](/details-cell/CL4023038) (CSI: 18.38), [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) (CSI: 14.89), and [corticothalamic-projecting glutamatergic cortical neurons](/details-cell/CL4023013) (CSI: 8.87), as well as [retinal ganglion cells](/details-cell/CL0000740). This strong association with diverse neuronal populations points towards a fundamental function in neuronal signaling, development, or stress response. Concurrently, [MAP3K4](/details-gene/4216) is highly significant in various cells of the hematopoietic and immune systems. Its prominence in terminally differentiated antibody-producing cells like [IgA plasma cells](/details-cell/CL0000987) and [plasmablasts](/details-cell/CL0000980), as well as in progenitor cells like [erythroblasts](/details-cell/CL0000765) and [common dendritic progenitors](/details-cell/CL0001029), suggests a continuous requirement for its signaling activity throughout hematopoiesis and immune cell function. Its role extends to specialized T cell subsets, as indicated by its significance in [T-helper 17 cells](/details-cell/CL0000899). Beyond these two major systems, [MAP3K4](/details-gene/4216) is also significant in specialized epithelial and mesenchymal cells, including [enteroendocrine cells](/details-cell/CL0000164), [lung ciliated cells](/details-cell/CL1000271), [myoepithelial cells](/details-cell/CL0000185), and [alveolar adventitial fibroblasts](/details-cell/CL4028006). This broad but specific expression pattern highlights its role as a key intracellular signal transducer essential for the function of a wide array of specialized cell types. ## Pathways and Molecular Function Functionally, [MAP3K4](/details-gene/4216) is a core component of intracellular signal transduction. Gene Ontology annotations confirm its molecular function as a [MAP kinase kinase kinase activity](/details-go/GO:0004709) and [protein serine kinase activity](/details-go/GO:0106310), requiring [ATP binding](/details-go/GO:0005524) for its catalytic function. It is primarily localized to the [cytoplasm](/details-go/GO:0005737) and the [perinuclear region of cytoplasm](/details-go/GO:0048471). The biological processes mediated by [MAP3K4](/details-gene/4216) are centered on the activation of stress-responsive signaling pathways. It is a key upstream activator in the [MAPK cascade](/details-go/GO:0000165), specifically contributing to the [p38MAPK cascade](/details-go/GO:0038066) and showing [positive regulation of JNK kinase activity](/details-go/GO:0043507). This is consistent with early research identifying it as a mediator of stress-induced signaling [Link](https://doi.org/10.1093/emboj/16.16.4973). Beyond stress responses, it is implicated in broader developmental and regulatory processes, including [placenta development](/details-go/GO:0001890), [chorionic trophoblast cell differentiation](/details-go/GO:0060718), and the [regulation of gene expression](/details-go/GO:0010468). ## Research Directions The widespread yet cell-type-specific significance of [MAP3K4](/details-gene/4216) suggests nuanced roles that warrant further investigation. Its established function as a stress-activated kinase, combined with its high significance in diverse neuronal and immune cells, opens several avenues for future research. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [MAP3K4](/details-gene/4216) in multiple distinct neuronal subtypes, such as cortical glutamatergic neurons and retinal ganglion cells, suggests it may regulate neuron-type specific stress responses or synaptic functions, rather than acting as a generic cell survival factor. 2. Given its significance in both hematopoietic progenitors ([erythroblast](/details-cell/CL0000765), [common dendritic progenitor](/details-cell/CL0001029)) and terminally differentiated immune cells ([IgA plasma cell](/details-cell/CL0000987)), [MAP3K4](/details-gene/4216) likely functions as a critical signaling node at multiple checkpoints during hematopoietic differentiation and subsequent effector immune responses. A key experiment to test the first hypothesis could involve the use of conditional knockout mouse models. Specifically, generating a mouse line where [MAP3K4](/details-gene/4216) is selectively deleted in excitatory cortical neurons (e.g., using a Camk2a-Cre driver) would allow for a detailed investigation of its role. Following deletion, neuronal function could be assessed using electrophysiological recordings of synaptic activity, and cellular responses to excitotoxic or oxidative stress could be quantified by measuring apoptosis rates and activation of downstream targets like p38 and JNK. From a therapeutic perspective, [MAP3K4](/details-gene/4216), as a protein kinase, belongs to a highly druggable class of proteins. Its central role in the p38/JNK stress pathways, which are implicated in inflammatory diseases and cancer, makes it a potential therapeutic target. However, its broad expression across critical cell types, including various neurons, suggests that systemic inhibition could lead to significant neurotoxicity or immunosuppressive side effects. Therefore, the therapeutic potential of targeting [MAP3K4](/details-gene/4216) likely lies in indications where targeted delivery (e.g., to a tumor) is possible or in diseases where the risk of side effects is acceptable. The strategy would focus on kinase inhibition to dampen pathological hyperactivation of stress signaling pathways.

Genular Protein ID: 1958634124

Symbol: M3K4_HUMAN

Name: Mitogen-activated protein kinase kinase kinase 4

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 9305639

Title: A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways.

PubMed ID: 9305639

DOI: 10.1093/emboj/16.16.4973

PubMed ID: 9039502

Title: Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.

PubMed ID: 9039502

DOI: 10.1093/dnares/3.5.321

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 12052864

Title: Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding.

PubMed ID: 12052864

DOI: 10.1128/mcb.22.13.4544-4555.2002

PubMed ID: 15262978

Title: The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms.

PubMed ID: 15262978

DOI: 10.1074/jbc.m404598200

PubMed ID: 16157600

Title: MEKK4 is an effector of the embryonic TRAF4 for JNK activation.

PubMed ID: 16157600

DOI: 10.1074/jbc.c500260200

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20221403

Title: Phosphorylation of human tristetraprolin in response to its interaction with the Cbl interacting protein CIN85.

PubMed ID: 20221403

DOI: 10.1371/journal.pone.0009588

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 1608
  • Mass: 181685
  • Checksum: C22294914945EA91
  • Sequence:
  • MREAAAALVP PPAFAVTPAA AMEEPPPPPP PPPPPPEPET ESEPECCLAA RQEGTLGDSA 
    CKSPESDLED FSDETNTENL YGTSPPSTPR QMKRMSTKHQ RNNVGRPASR SNLKEKMNAP 
    NQPPHKDTGK TVENVEEYSY KQEKKIRAAL RTTERDRKKN VQCSFMLDSV GGSLPKKSIP 
    DVDLNKPYLS LGCSNAKLPV SVPMPIARPA RQTSRTDCPA DRLKFFETLR LLLKLTSVSK 
    KKDREQRGQE NTSGFWLNRS NELIWLELQA WHAGRTINDQ DFFLYTARQA IPDIINEILT 
    FKVDYGSFAF VRDRAGFNGT SVEGQCKATP GTKIVGYSTH HEHLQRQRVS FEQVKRIMEL 
    LEYIEALYPS LQALQKDYEK YAAKDFQDRV QALCLWLNIT KDLNQKLRIM GTVLGIKNLS 
    DIGWPVFEIP SPRPSKGNEP EYEGDDTEGE LKELESSTDE SEEEQISDPR VPEIRQPIDN 
    SFDIQSRDCI SKKLERLESE DDSLGWGAPD WSTEAGFSRH CLTSIYRPFV DKALKQMGLR 
    KLILRLHKLM DGSLQRARIA LVKNDRPVEF SEFPDPMWGS DYVQLSRTPP SSEEKCSAVS 
    WEELKAMDLP SFEPAFLVLC RVLLNVIHEC LKLRLEQRPA GEPSLLSIKQ LVRECKEVLK 
    GGLLMKQYYQ FMLQEVLEDL EKPDCNIDAF EEDLHKMLMV YFDYMRSWIQ MLQQLPQASH 
    SLKNLLEEEW NFTKEITHYI RGGEAQAGKL FCDIAGMLLK STGSFLEFGL QESCAEFWTS 
    ADDSSASDEI RRSVIEISRA LKELFHEARE RASKALGFAK MLRKDLEIAA EFRLSAPVRD 
    LLDVLKSKQY VKVQIPGLEN LQMFVPDTLA EEKSIILQLL NAAAGKDCSK DSDDVLIDAY 
    LLLTKHGDRA RDSEDSWGTW EAQPVKVVPQ VETVDTLRSM QVDNLLLVVM QSAHLTIQRK 
    AFQQSIEGLM TLCQEQTSSQ PVIAKALQQL KNDALELCNR ISNAIDRVDH MFTSEFDAEV 
    DESESVTLQQ YYREAMIQGY NFGFEYHKEV VRLMSGEFRQ KIGDKYISFA RKWMNYVLTK 
    CESGRGTRPR WATQGFDFLQ AIEPAFISAL PEDDFLSLQA LMNECIGHVI GKPHSPVTGL 
    YLAIHRNSPR PMKVPRCHSD PPNPHLIIPT PEGFSTRSMP SDARSHGSPA AAAAAAAAAV 
    AASRPSPSGG DSVLPKSISS AHDTRGSSVP ENDRLASIAA ELQFRSLSRH SSPTEERDEP 
    AYPRGDSSGS TRRSWELRTL ISQSKDTASK LGPIEAIQKS VRLFEEKRYR EMRRKNIIGQ 
    VCDTPKSYDN VMHVGLRKVT FKWQRGNKIG EGQYGKVYTC ISVDTGELMA MKEIRFQPND 
    HKTIKETADE LKIFEGIKHP NLVRYFGVEL HREEMYIFME YCDEGTLEEV SRLGLQEHVI 
    RLYSKQITIA INVLHEHGIV HRDIKGANIF LTSSGLIKLG DFGCSVKLKN NAQTMPGEVN 
    STLGTAAYMA PEVITRAKGE GHGRAADIWS LGCVVIEMVT GKRPWHEYEH NFQIMYKVGM 
    GHKPPIPERL SPEGKDFLSH CLESDPKMRW TASQLLDHSF VKVCTDEE

Genular Protein ID: 2253829729

Symbol: Q9P1M2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 544
  • Mass: 62067
  • Checksum: E55CB8CF9E3055A7
  • Sequence:
  • MFTSEFDAEV DESESVTLQQ YYREAMIQGY NFGFEYHKEV VRLMSGEFRQ KIGDKYISFA 
    RKWMNYVLTK CESGRGTRPR WATQGFDFLQ AIEPAFISAL PEDDFLSLQA LMNECIGHVI 
    GKPHSPVTAI HRNSPRPMKV PRCHSDPPNP HLIIPTPEGF RGSSVPENDR LASIAAELQF 
    RSLSRHSSPT EERDEPAYPR GDSSGSTRRS WELRTLISQS KDTASKLGPI EAIQKSVRLF 
    EEKRYREMRR KNIIGQVCDT PKSYDNVMHV GLRKVTFKWQ RGNKIGEGQY GKVYTCISVD 
    TGELMAMKEI RFQPNDHKTI KETADELKIF EGIKHPNLVR YFGVELHREE MYIFMEYCDE 
    GTLEDVSRLG LQEHVIRLYS KQITIAINVL HEHGIVHRDI KGANIFLTSS GLIKLGDFGC 
    SVKLKNNAQT MPGEVNSTLG TAAYMAPEVI TRAKGEGHGR AADIWSLGCV VIEMVTGKRP 
    WHEYEHNFQI MYKVGMGHKP PIPERLSPEG KDFLSHCLES DPKMRWTASQ LLDHSFVKVC 
    TDEE