Details for: SMAD5

Gene ID: 4090

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: SMAD5

Ensembl ID: ENSG00000113658

Description: SMAD family member 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • hepatocyte CL0000182
    CSI 18.77
    rCSI 33.59%
    PRS 23.98
  • cardiac muscle cell CL0000746
    CSI 12.2
    rCSI 17.51%
    PRS 20.23
  • endothelial cell of placenta CL0009092
    CSI 7.27
    rCSI 35.82%
    PRS 34.52
  • enterocyte CL0000584
    CSI 6.07
    rCSI 9.78%
    PRS 37.35
  • retinal ganglion cell CL0000740
    CSI 5.94
    rCSI 13.12%
    PRS 18.52
  • transit amplifying cell CL0009010
    CSI 5.43
    rCSI 8.31%
    PRS 40.62
  • paneth cell CL0000510
    CSI 5.35
    rCSI 7.9%
    PRS 39.57
  • transit amplifying cell of colon CL0009011
    CSI 5.32
    rCSI 6.25%
    PRS 29.46
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 5.29
    rCSI 31.14%
    PRS 16.46
  • fallopian tube secretory epithelial cell CL4030006
    CSI 5.27
    rCSI 5.07%
    PRS 26.71
  • mature B cell CL0000785
    CSI 5.25
    rCSI 4.57%
    PRS 32.39
  • lung pericyte CL0009089
    CSI 4.57
    rCSI 12.07%
    PRS 30.72
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 4.09
    rCSI 9.83%
    PRS 39.97
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.96
    rCSI 24.72%
    PRS 20.57
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.82
    rCSI 8.55%
    PRS 16.27
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.67
    rCSI 13.22%
    PRS 14.82
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3.53
    rCSI 9.13%
    PRS 23.84
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.5
    rCSI 4.49%
    PRS 24.63
  • type B pancreatic cell CL0000169
    CSI 3.27
    rCSI 7.23%
    PRS 23.81
  • pulmonary artery endothelial cell CL1001568
    CSI 3.17
    rCSI 4.31%
    PRS 37.55
  • IgA plasma cell CL0000987
    CSI 3.16
    rCSI 3.24%
    PRS 44.7
  • mature T cell CL0002419
    CSI 3.15
    rCSI 2.45%
    PRS 37.7
  • ON-bipolar cell CL0000749
    CSI 3.15
    rCSI 4.68%
    PRS 29.51
  • ionocyte CL0005006
    CSI 3.12
    rCSI 3.35%
    PRS 23.79
  • goblet cell CL0000160
    CSI 3.04
    rCSI 2.87%
    PRS 27
  • mesenchymal cell CL0008019
    CSI 2.9
    rCSI 7.37%
    PRS 25.2
  • cerebellar granule cell CL0001031
    CSI 2.85
    rCSI 4.19%
    PRS 23.77
  • paneth cell of epithelium of small intestine CL1000343
    CSI 2.84
    rCSI 7.96%
    PRS 39.28
  • glioblast CL0000030
    CSI 2.62
    rCSI 4.18%
    PRS 21.99
  • common dendritic progenitor CL0001029
    CSI 2.61
    rCSI 3.28%
    PRS 33.28
  • intrahepatic cholangiocyte CL0002538
    CSI 2.61
    rCSI 6.25%
    PRS 43.26
  • interstitial cell of Cajal CL0002088
    CSI 2.59
    rCSI 3.3%
    PRS 29.59
  • pancreatic epsilon cell CL0005019
    CSI 2.59
    rCSI 12.06%
    PRS 51.18
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.57
    rCSI 1.79%
    PRS 27.39
  • mesangial cell CL0000650
    CSI 2.43
    rCSI 9.91%
    PRS 36.13
  • epithelial cell of lung CL0000082
    CSI 2.34
    rCSI 1.94%
    PRS 24.55
  • skeletal muscle satellite cell CL0000594
    CSI 2.28
    rCSI 6.67%
    PRS 62.21
  • acinar cell CL0000622
    CSI 2.25
    rCSI 3.3%
    PRS 33.56
  • brush cell of tracheobronchial tree CL0002075
    CSI 2.22
    rCSI 6.59%
    PRS 35.12
  • intestine goblet cell CL0019031
    CSI 2.22
    rCSI 1.97%
    PRS 26.06
  • type L enteroendocrine cell CL0002279
    CSI 2.2
    rCSI 4.14%
    PRS 47.15
  • group 3 innate lymphoid cell CL0001071
    CSI 2.17
    rCSI 1.63%
    PRS 27.62
  • fibroblast of cardiac tissue CL0002548
    CSI 2.16
    rCSI 10.33%
    PRS 22.23
  • lung endothelial cell CL1001567
    CSI 2.15
    rCSI 5.01%
    PRS 54.17
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.14
    rCSI 1.44%
    PRS 32.03
  • midzonal region hepatocyte CL0019028
    CSI 2.13
    rCSI 4.99%
    PRS 35.75
  • Kupffer cell CL0000091
    CSI 2.1
    rCSI 4.81%
    PRS 25.23
  • early lymphoid progenitor CL0000936
    CSI 2.1
    rCSI 1.84%
    PRS 29.61
  • glycinergic amacrine cell CL4030028
    CSI 2.07
    rCSI 5.38%
    PRS 25.75
  • perivascular cell CL4033054
    CSI 2.06
    rCSI 2.81%
    PRS 29.06
  • pancreatic D cell CL0000173
    CSI 2.06
    rCSI 2.02%
    PRS 27.65
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.05
    rCSI 2.45%
    PRS 15.47
  • ciliated cell CL0000064
    CSI 2
    rCSI 3.23%
    PRS 25.75
  • centrilobular region hepatocyte CL0019029
    CSI 1.99
    rCSI 5.2%
    PRS 37.25
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.98
    rCSI 2.46%
    PRS 14.7
  • respiratory hillock cell CL4030023
    CSI 1.95
    rCSI 3.48%
    PRS 40.78
  • pro-B cell CL0000826
    CSI 1.95
    rCSI 1.61%
    PRS 26.18
  • endocardial cell CL0002350
    CSI 1.94
    rCSI 9.28%
    PRS 30.57
  • multi-ciliated epithelial cell CL0005012
    CSI 1.92
    rCSI 1.92%
    PRS 22.11
  • mesodermal cell CL0000222
    CSI 1.92
    rCSI 2.3%
    PRS 24.98
  • secretory cell CL0000151
    CSI 1.91
    rCSI 1.99%
    PRS 26.47
  • pancreatic A cell CL0000171
    CSI 1.9
    rCSI 1.99%
    PRS 27.4
  • melanocyte CL0000148
    CSI 1.88
    rCSI 1.39%
    PRS 22.12
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 1.87
    rCSI 2.65%
    PRS 23.94
  • brush cell CL0002204
    CSI 1.84
    rCSI 3.65%
    PRS 55.68
  • renal beta-intercalated cell CL0002201
    CSI 1.83
    rCSI 4.37%
    PRS 28.72
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.81
    rCSI 6.86%
    PRS 16.29
  • hematopoietic precursor cell CL0008001
    CSI 1.78
    rCSI 1.83%
    PRS 40.38
  • epithelial cell of lower respiratory tract CL0002632
    CSI 1.77
    rCSI 1.38%
    PRS 25.1
  • radial glial cell CL0000681
    CSI 1.76
    rCSI 2.45%
    PRS 26
  • choroid plexus epithelial cell CL0000706
    CSI 1.76
    rCSI 2.88%
    PRS 19.98
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.75
    rCSI 4%
    PRS 26.16
  • renal alpha-intercalated cell CL0005011
    CSI 1.75
    rCSI 2.34%
    PRS 32.75
  • class switched memory B cell CL0000972
    CSI 1.73
    rCSI 1.29%
    PRS 41.92
  • pulmonary capillary endothelial cell CL4028001
    CSI 1.73
    rCSI 3.29%
    PRS 39.97
  • squamous epithelial cell CL0000076
    CSI 1.72
    rCSI 4.09%
    PRS 31.29
  • stem cell CL0000034
    CSI 1.69
    rCSI 1.63%
    PRS 19.11
  • fibroblast of lung CL0002553
    CSI 1.68
    rCSI 1.56%
    PRS 25.79
  • skin fibroblast CL0002620
    CSI 1.68
    rCSI 1.45%
    PRS 37.25
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.67
    rCSI 2.6%
    PRS 36.95
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.66
    rCSI 1.92%
    PRS 22.33
  • foveolar cell of stomach CL0002179
    CSI 1.63
    rCSI 3.48%
    PRS 39.76
  • megakaryocyte CL0000556
    CSI 1.62
    rCSI 7.04%
    PRS 42.02
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.61
    rCSI 8.07%
    PRS 33.93
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.6
    rCSI 1.39%
    PRS 28.92
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.59
    rCSI 1.89%
    PRS 43.47
  • hepatic stellate cell CL0000632
    CSI 1.58
    rCSI 5.92%
    PRS 21.71
  • blood vessel endothelial cell CL0000071
    CSI 1.58
    rCSI 3.27%
    PRS 25.53
  • bronchus fibroblast of lung CL2000093
    CSI 1.57
    rCSI 1.27%
    PRS 26.92
  • lung neuroendocrine cell CL1000223
    CSI 1.56
    rCSI 2.31%
    PRS 29.33
  • cerebral cortex endothelial cell CL1001602
    CSI 1.55
    rCSI 2.68%
    PRS 19.8
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.54
    rCSI 2.79%
    PRS 38.91
  • ciliated epithelial cell CL0000067
    CSI 1.53
    rCSI 1.35%
    PRS 18.9
  • neural crest cell CL0011012
    CSI 1.53
    rCSI 1.21%
    PRS 17.78
  • duct epithelial cell CL0000068
    CSI 1.52
    rCSI 2.22%
    PRS 27.38
  • alveolar type 1 fibroblast cell CL4028004
    CSI 1.52
    rCSI 1.66%
    PRS 28.83
  • M cell of gut CL0000682
    CSI 1.51
    rCSI 1.6%
    PRS 41.79
  • alveolar adventitial fibroblast CL4028006
    CSI 1.5
    rCSI 2.37%
    PRS 26.01
  • peripheral nervous system neuron CL2000032
    CSI 1.5
    rCSI 2.04%
    PRS 22.38
  • Mueller cell CL0000636
    CSI 1.48
    rCSI 3.37%
    PRS 22.11
  • pluripotent stem cell CL0002248
    CSI 0.1
    rCSI 3.5%
    PRS 51.2%
  • direct pathway medium spiny neuron CL4023026
    CSI 0.2
    rCSI 3.9%
    PRS 14.5%
  • mesenchymal stem cell CL0000134
    CSI 0.2
    rCSI 2.0%
    PRS 43.5%
  • retinal cone cell CL0000573
    CSI 0.2
    rCSI 0.3%
    PRS 19.8%
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.2
    rCSI 5.1%
    PRS 15.4%
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.3
    rCSI 2.1%
    PRS 46.8%
  • respiratory goblet cell CL0002370
    CSI 0.3
    rCSI 3.5%
    PRS 46.6%
  • pancreatic stellate cell CL0002410
    CSI 0.3
    rCSI 2.0%
    PRS 37.1%
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.4
    rCSI 1.1%
    PRS 17.9%
  • retinal pigment epithelial cell CL0002586
    CSI 0.4
    rCSI 0.7%
    PRS 26.7%
  • intestinal crypt stem cell of colon CL0009043
    CSI 0.4
    rCSI 2.7%
    PRS 45.2%
  • H1 horizontal cell CL0004217
    CSI 0.4
    rCSI 1.5%
    PRS 32.5%
  • enteroendocrine cell of colon CL0009042
    CSI 0.4
    rCSI 1.8%
    PRS 56.0%
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.4
    rCSI 1.2%
    PRS 16.5%
  • type EC enteroendocrine cell CL0000577
    CSI 0.4
    rCSI 1.4%
    PRS 40.1%
  • luminal cell of prostate epithelium CL0002340
    CSI 0.4
    rCSI 2.2%
    PRS 42.5%
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.5
    rCSI 1.2%
    PRS 15.4%
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.5
    rCSI 1.5%
    PRS 28.8%
  • renal interstitial pericyte CL1001318
    CSI 0.5
    rCSI 1.4%
    PRS 24.2%
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.5
    rCSI 0.9%
    PRS 15.7%
  • transit amplifying cell of small intestine CL0009012
    CSI 0.6
    rCSI 2.4%
    PRS 45.2%
  • parietal epithelial cell CL1000452
    CSI 0.6
    rCSI 1.5%
    PRS 21.5%
  • H2 horizontal cell CL0004218
    CSI 0.6
    rCSI 2.9%
    PRS 27.6%
  • fibroblast of breast CL4006000
    CSI 0.6
    rCSI 2.5%
    PRS 54.9%
  • acinar cell of salivary gland CL0002623
    CSI 0.6
    rCSI 14.0%
    PRS 46.5%
  • amacrine cell CL0000561
    CSI 0.6
    rCSI 1.8%
    PRS 20.2%
  • mucus secreting cell CL0000319
    CSI 0.6
    rCSI 1.0%
    PRS 33.1%
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.6
    rCSI 1.5%
    PRS 18.1%
  • endothelial cell of uterus CL0009095
    CSI 0.6
    rCSI 4.7%
    PRS 58.7%
  • retina horizontal cell CL0000745
    CSI 0.7
    rCSI 1.0%
    PRS 23.7%
  • colon goblet cell CL0009039
    CSI 0.7
    rCSI 1.7%
    PRS 37.4%
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 0.7
    rCSI 1.9%
    PRS 33.3%
  • nasal mucosa goblet cell CL0002480
    CSI 0.7
    rCSI 0.8%
    PRS 36.5%
  • enteroendocrine cell of small intestine CL0009006
    CSI 0.8
    rCSI 1.7%
    PRS 38.2%
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 0.8
    rCSI 0.6%
    PRS 24.3%
  • cardiac neuron CL0010022
    CSI 0.8
    rCSI 2.5%
    PRS 22.0%
  • keratocyte CL0002363
    CSI 0.8
    rCSI 1.9%
    PRS 36.8%
  • pancreatic acinar cell CL0002064
    CSI 0.8
    rCSI 1.1%
    PRS 28.3%
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 0.8
    rCSI 1.5%
    PRS 50.6%
  • forebrain radial glial cell CL0013000
    CSI 0.8
    rCSI 2.6%
    PRS 34.8%
  • corneal epithelial cell CL0000575
    CSI 0.8
    rCSI 2.4%
    PRS 43.1%
  • IgG plasma cell CL0000985
    CSI 0.8
    rCSI 1.0%
    PRS 43.2%
  • pancreatic ductal cell CL0002079
    CSI 0.8
    rCSI 1.6%
    PRS 26.6%
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 0.9
    rCSI 1.5%
    PRS 15.4%
  • tracheobronchial smooth muscle cell CL0019019
    CSI 0.9
    rCSI 1.5%
    PRS 32.9%
  • stromal cell CL0000499
    CSI 0.9
    rCSI 2.5%
    PRS 31.6%
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.0
    rCSI 1.2%
    PRS 16.3%
  • central nervous system neuron CL2000029
    CSI 1.0
    rCSI 7.1%
    PRS 16.4%
  • neuroendocrine cell CL0000165
    CSI 1.0
    rCSI 3.8%
    PRS 46.3%
  • cholangiocyte CL1000488
    CSI 1.0
    rCSI 5.9%
    PRS 42.5%
  • common myeloid progenitor CL0000049
    CSI 1.0
    rCSI 0.8%
    PRS 26.0%
  • respiratory basal cell CL0002633
    CSI 1.0
    rCSI 1.0%
    PRS 30.4%
  • chondrocyte CL0000138
    CSI 1.0
    rCSI 1.6%
    PRS 21.7%
  • small intestine goblet cell CL1000495
    CSI 1.0
    rCSI 2.2%
    PRS 34.1%
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.0
    rCSI 1.6%
    PRS 17.1%
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.0
    rCSI 2.6%
    PRS 19.7%
  • intestinal tuft cell CL0019032
    CSI 1.0
    rCSI 1.6%
    PRS 29.4%
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.1
    rCSI 4.2%
    PRS 41.7%
  • lung ciliated cell CL1000271
    CSI 1.1
    rCSI 1.3%
    PRS 19.1%
  • podocyte CL0000653
    CSI 1.1
    rCSI 4.9%
    PRS 25.1%
  • tuft cell of colon CL0009041
    CSI 1.1
    rCSI 2.6%
    PRS 46.6%
  • respiratory suprabasal cell CL4033048
    CSI 1.1
    rCSI 1.4%
    PRS 29.7%
  • mucous neck cell CL0000651
    CSI 1.1
    rCSI 1.6%
    PRS 39.4%
  • P/D1 enteroendocrine cell CL0002268
    CSI 1.1
    rCSI 6.0%
    PRS 52.9%
  • stromal cell of ovary CL0002132
    CSI 1.1
    rCSI 3.1%
    PRS 40.9%
  • placental villous trophoblast CL2000060
    CSI 1.1
    rCSI 1.7%
    PRS 24.2%
  • regular atrial cardiac myocyte CL0002129
    CSI 1.1
    rCSI 3.6%
    PRS 26.6%
  • keratinocyte CL0000312
    CSI 1.1
    rCSI 1.0%
    PRS 30.3%
  • myeloid leukocyte CL0000766
    CSI 1.2
    rCSI 1.1%
    PRS 26.9%
  • lung secretory cell CL1000272
    CSI 1.2
    rCSI 2.8%
    PRS 24.0%
  • rod bipolar cell CL0000751
    CSI 1.2
    rCSI 2.1%
    PRS 21.4%
  • vascular associated smooth muscle cell CL0000359
    CSI 1.2
    rCSI 3.8%
    PRS 30.3%
  • conjunctival epithelial cell CL1000432
    CSI 1.2
    rCSI 1.8%
    PRS 26.0%
  • Bergmann glial cell CL0000644
    CSI 1.2
    rCSI 1.6%
    PRS 25.2%
  • Hofbauer cell CL3000001
    CSI 1.2
    rCSI 2.2%
    PRS 32.8%
  • adventitial cell CL0002503
    CSI 1.2
    rCSI 2.9%
    PRS 37.3%
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.2
    rCSI 2.2%
    PRS 22.0%
  • pancreatic PP cell CL0002275
    CSI 1.2
    rCSI 4.8%
    PRS 41.9%
  • interneuron CL0000099
    CSI 1.2
    rCSI 2.5%
    PRS 19.2%
  • club cell CL0000158
    CSI 1.2
    rCSI 1.8%
    PRS 28.7%
  • cardiac endothelial cell CL0010008
    CSI 1.2
    rCSI 5.0%
    PRS 24.1%
  • colon epithelial cell CL0011108
    CSI 1.2
    rCSI 1.3%
    PRS 24.1%
  • BEST4+ enteroycte CL4030026
    CSI 1.3
    rCSI 1.6%
    PRS 27.6%
  • adipocyte CL0000136
    CSI 1.3
    rCSI 1.6%
    PRS 24.9%
  • Schwann cell CL0002573
    CSI 1.3
    rCSI 3.6%
    PRS 28.2%
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 1.3
    rCSI 3.7%
    PRS 30.0%
  • inhibitory interneuron CL0000498
    CSI 1.3
    rCSI 3.0%
    PRS 20.9%
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 1.3
    rCSI 3.4%
    PRS 24.4%
  • myoepithelial cell CL0000185
    CSI 1.3
    rCSI 3.3%
    PRS 31.6%
  • basal cell CL0000646
    CSI 1.3
    rCSI 1.8%
    PRS 28.0%
  • enteroendocrine cell CL0000164
    CSI 1.3
    rCSI 1.8%
    PRS 28.5%
  • precursor B cell CL0000817
    CSI 1.3
    rCSI 1.2%
    PRS 33.8%
  • periportal region hepatocyte CL0019026
    CSI 1.3
    rCSI 5.2%
    PRS 34.5%
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.4
    rCSI 1.2%
    PRS 23.5%
  • retinal bipolar neuron CL0000748
    CSI 1.4
    rCSI 2.5%
    PRS 18.9%
  • enteric smooth muscle cell CL0002504
    CSI 1.4
    rCSI 2.0%
    PRS 28.6%
  • extravillous trophoblast CL0008036
    CSI 1.4
    rCSI 1.7%
    PRS 22.7%
  • vascular leptomeningeal cell CL4023051
    CSI 1.4
    rCSI 2.5%
    PRS 20.1%
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.5
    rCSI 2.3%
    PRS 28.3%
  • intestinal epithelial cell CL0002563
    CSI 1.5
    rCSI 1.5%
    PRS 26.6%

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 [SMAD5](/details-gene/4090) (SMAD family member 5) is a protein-coding gene located on chromosome 5q31.1 that functions as a key intracellular signal transducer and transcription factor. As a member of the receptor-regulated SMAD (R-SMAD) family, it is a critical component of the Transforming Growth Factor-beta (TGF-beta) superfamily signaling pathways. Upon phosphorylation by Bone Morphogenetic Protein (BMP) type I receptors, [SMAD5](/details-gene/4090) forms a complex with SMAD4, translocates to the nucleus, and regulates the transcription of target genes involved in a wide array of developmental processes. **Overall**, its expression is most significant in `[hepatocyte](/details-cell/CL0000182)`s and `[cardiac muscle cell](/details-cell/CL0000746)`s, suggesting fundamental roles in liver physiology and cardiac function, consistent with its established involvement in cell differentiation, morphogenesis, and homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [SMAD5](/details-gene/4090) highlights its importance in diverse and metabolically active tissues. **Overall**, the gene demonstrates the highest significance in `[hepatocyte](/details-cell/CL0000182)` (CSI: 18.77) and `[cardiac muscle cell](/details-cell/CL0000746)` (CSI: 12.20), indicating a crucial role in maintaining the function and structure of the liver and heart. Beyond these primary cell types, [SMAD5](/details-gene/4090) shows significant expression in various other cellular contexts, suggesting broad functional relevance: * **Epithelial and Secretory Cells:** High significance in `[enterocyte](/details-cell/CL0000584)`s of the intestine and `[fallopian tube secretory epithelial cell](/details-cell/CL4030006)`s points to a role in epithelial tissue maintenance and function. * **Progenitor and Stem Cells:** Its relevance in `[transit amplifying cell](/details-cell/CL0009010)`s and `[hematopoietic multipotent progenitor cell](/details-cell/CL0000837)`s is consistent with its function in driving cell differentiation programs, such as erythropoiesis [Link](https://doi.org/10.1006/bcmd.2002.0487). * **Nervous System:** Significant expression in neuronal subtypes like `[retinal ganglion cell](/details-cell/CL0000740)`s and `[corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013)`s suggests a role in neuronal development or maintenance. This widespread but distinct expression pattern underscores the role of [SMAD5](/details-gene/4090) as a central mediator of BMP signaling that directs lineage-specific differentiation and maintains tissue homeostasis across multiple organ systems. ## Pathways and Molecular Function Functionally, [SMAD5](/details-gene/4090) is intrinsically linked to the `[Signaling by bmp](/details-pathway/R-HSA-201451)` pathway, a branch of the `[Signaling by tgfb family members](/details-pathway/R-HSA-9006936)` super-pathway. Its primary molecular function is `[Dna-binding transcription factor activity, rna polymerase ii-specific](/details-ontology/GO:0000981)`, enabling it to either activate or repress gene expression following a signaling cascade. The biological processes governed by [SMAD5](/details-gene/4090) are extensive and predominantly related to development and differentiation. Key annotated processes include: * **Skeletal Development:** It is a well-established mediator of `[Bone development](/details-ontology/GO:0060348)` and `[Cartilage development](/details-ontology/GO:0051216)`, playing a critical role in `[Osteoblast differentiation](/details-ontology/GO:0001649)` as demonstrated in mesenchymal precursor cells [Link](https://doi.org/10.1074/jbc.273.4.1872). * **Hematopoiesis:** It is essential for `[Erythrocyte differentiation](/details-ontology/GO:0030218)`, with studies showing that its inhibition blocks BMP4-induced erythropoiesis in human hematopoietic progenitors [Link](https://doi.org/10.1006/bcmd.2002.0487). * **Organogenesis:** Its involvement in `[Anatomical structure morphogenesis](/details-ontology/GO:0009653)` is exemplified by its roles in `[Cardiac conduction system development](/details-ontology/GO:0003161)` and `[Ureteric bud development](/details-ontology/GO:0001657)`. Upon activation, [SMAD5](/details-gene/4090) translocates from the `[Cytoplasm](/details-ontology/GO:0005737)` to the `[Nucleus](/details-ontology/GO:0005634)`, where it forms a `[Heteromeric smad protein complex](/details-ontology/GO:0071144)` with SMAD4 to bind DNA and regulate transcription. Interestingly, it has also been reported to localize to the `[Mitochondrion](/details-ontology/GO:0005739)` in certain cell types, suggesting non-canonical, transcription-independent functions [Link](https://doi.org/10.1016/s0006-291x(03)01139-2). ## Research Directions The role of [SMAD5](/details-gene/4090) as a central signaling node and its association with a chromosomal region frequently deleted in cancer provides fertile ground for future investigation. Early research identified it as a potential tumor suppressor candidate in myeloid leukemia [Link](https://doi.org/10.1038/sj.leu.2400750). Based on the available data, several testable hypotheses can be proposed: 1. **Cardiac Homeostasis:** Given its exceptionally high significance in `[cardiac muscle cell](/details-cell/CL0000746)`s, [SMAD5](/details-gene/4090) may be essential for maintaining adult cardiomyocyte structural integrity and metabolic function, and its conditional knockout in adult mice could lead to cardiomyopathy. 2. **Hepatic Regeneration:** The top ranking of [SMAD5](/details-gene/4090) in `[hepatocyte](/details-cell/CL0000182)`s suggests that it is a critical mediator of liver regeneration, and its inhibition would likely impair the proliferative response of hepatocytes following partial hepatectomy. 3. **Leukemogenesis:** Based on its established role in erythropoiesis and its chromosomal location, loss of [SMAD5](/details-gene/4090) function in `[hematopoietic multipotent progenitor cell](/details-cell/CL0000837)`s may serve as a key event that blocks differentiation and promotes clonal expansion, contributing to the pathogenesis of 5q-syndrome, a subtype of myelodysplastic syndrome (MDS). A key experiment to test the third hypothesis would be to use CRISPR-Cas9 to inactivate [SMAD5](/details-gene/4090) in primary human CD34+ hematopoietic stem and progenitor cells. These engineered cells could then be cultured in vitro under conditions that promote erythroid differentiation. The effect of [SMAD5](/details-gene/4090) loss would be quantified by assessing the block in maturation via flow cytometry (monitoring CD71/CD235a expression), analyzing proliferation rates, and performing RNA-sequencing to identify downstream transcriptional networks disrupted by the loss of SMAD5-mediated signaling. As a potential therapeutic target, [SMAD5](/details-gene/4090) is challenging due to its role as an intracellular transcription factor. However, because it functions as a tumor suppressor, therapeutic strategies would focus on **activation** or restoration of its pathway rather than inhibition. In hematologic malignancies characterized by [SMAD5](/details-gene/4090) haploinsufficiency, small molecules that activate BMP receptors or inhibit endogenous pathway antagonists (e.g., Noggin) could potentially restore sufficient signaling through the remaining [SMAD5](/details-gene/4090) allele, thereby promoting differentiation and antagonizing the leukemic phenotype.

Genular Protein ID: 3828878677

Symbol: SMAD5_HUMAN

Name: Mothers against decapentaplegic homolog 5

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 8673135

Title: Mad-related genes in the human.

PubMed ID: 8673135

DOI: 10.1038/ng0796-347

PubMed ID: 9288787

Title: Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor.

PubMed ID: 9288787

PubMed ID: 9264367

Title: Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60.

PubMed ID: 9264367

DOI: 10.1038/sj.leu.2400750

PubMed ID: 9484787

Title: hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors.

PubMed ID: 9484787

DOI: 10.1038/sj.onc.1201614

PubMed ID: 9442019

Title: Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12.

PubMed ID: 9442019

DOI: 10.1074/jbc.273.4.1872

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: 9759503

Title: TGF-beta signal transduction.

PubMed ID: 9759503

DOI: 10.1146/annurev.biochem.67.1.753

PubMed ID: 10647776

Title: Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells.

PubMed ID: 10647776

DOI: 10.1016/s1359-6101(99)00012-x

PubMed ID: 10708948

Title: The Smad pathway.

PubMed ID: 10708948

DOI: 10.1016/s1359-6101(99)00024-6

PubMed ID: 10708949

Title: TGF-beta signaling by Smad proteins.

PubMed ID: 10708949

DOI: 10.1016/s1359-6101(99)00025-8

PubMed ID: 12370310

Title: Identification of mZnf8, a mouse Kruppel-like transcriptional repressor, as a novel nuclear interaction partner of Smad1.

PubMed ID: 12370310

DOI: 10.1128/mcb.22.21.7633-7644.2002

PubMed ID: 12064918

Title: Inhibition of Smad5 in human hematopoietic progenitors blocks erythroid differentiation induced by BMP4.

PubMed ID: 12064918

DOI: 10.1006/bcmd.2002.0487

PubMed ID: 12849988

Title: Mitochondrial localization of Smad5 in a human chondrogenic cell line.

PubMed ID: 12849988

DOI: 10.1016/s0006-291x(03)01139-2

PubMed ID: 15107829

Title: Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression.

PubMed ID: 15107829

DOI: 10.1038/sj.onc.1207660

PubMed ID: 15647271

Title: The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines.

PubMed ID: 15647271

DOI: 10.1074/jbc.m411234200

PubMed ID: 16516194

Title: Hgs physically interacts with Smad5 and attenuates BMP signaling.

PubMed ID: 16516194

DOI: 10.1016/j.yexcr.2006.01.019

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

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: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 25755279

Title: Nuclear export of Smads by RanBP3L regulates bone morphogenetic protein signaling and mesenchymal stem cell differentiation.

PubMed ID: 25755279

DOI: 10.1128/mcb.00121-15

PubMed ID: 28675158

Title: Smad5 acts as an intracellular pH messenger and maintains bioenergetic homeostasis.

PubMed ID: 28675158

DOI: 10.1038/cr.2017.85

PubMed ID: 33510867

Title: Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes.

PubMed ID: 33510867

DOI: 10.1016/j.csbj.2020.12.044

Sequence Information:

  • Length: 465
  • Mass: 52258
  • Checksum: 4A1FD7EC7BD06728
  • Sequence:
  • MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG 
    QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE 
    VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP 
    NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP 
    MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 
    DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 
    NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW 
    GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS