Details for: HSPA5

Gene ID: 3309

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: HSPA5

Ensembl ID: ENSG00000044574

Description: heat shock protein family A (Hsp70) member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmablast CL0000980
    CSI 119.44
    rCSI 93.96%
    PRS 4.88
  • granulocyte monocyte progenitor cell CL0000557
    CSI 90.03
    rCSI 77.95%
    PRS 4.55
  • extravillous trophoblast CL0008036
    CSI 79.05
    rCSI 97.79%
    PRS 3.59
  • common myeloid progenitor CL0000049
    CSI 78.36
    rCSI 63.36%
    PRS 4.02
  • fallopian tube secretory epithelial cell CL4030006
    CSI 73.78
    rCSI 71.02%
    PRS 4.23
  • ciliated epithelial cell CL0000067
    CSI 70.7
    rCSI 62.17%
    PRS 2.95
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 68.6
    rCSI 61.95%
    PRS 3.61
  • colon epithelial cell CL0011108
    CSI 67.58
    rCSI 70.79%
    PRS 3.82
  • intestinal epithelial cell CL0002563
    CSI 64.96
    rCSI 67.9%
    PRS 4.35
  • pancreatic D cell CL0000173
    CSI 64.19
    rCSI 63.14%
    PRS 4.49
  • hematopoietic stem cell CL0000037
    CSI 62.66
    rCSI 41.65%
    PRS 4.89
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 60.78
    rCSI 40.51%
    PRS 11.57
  • pancreatic A cell CL0000171
    CSI 60.7
    rCSI 63.59%
    PRS 4.38
  • IgA plasma cell CL0000987
    CSI 55.02
    rCSI 56.32%
    PRS 7.77
  • placental villous trophoblast CL2000060
    CSI 54.89
    rCSI 84.81%
    PRS 3.84
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 54.7
    rCSI 36.85%
    PRS 4.98
  • epithelial cell of lower respiratory tract CL0002632
    CSI 53.92
    rCSI 41.8%
    PRS 3.9
  • stem cell CL0000034
    CSI 53.35
    rCSI 51.44%
    PRS 2.06
  • plasma cell CL0000786
    CSI 51.81
    rCSI 67.91%
    PRS 22.12
  • M cell of gut CL0000682
    CSI 49.24
    rCSI 52.32%
    PRS 7.32
  • intestine goblet cell CL0019031
    CSI 47.47
    rCSI 42.14%
    PRS 4.1
  • promyelocyte CL0000836
    CSI 46.69
    rCSI 67.34%
    PRS 5.7
  • plasmacytoid dendritic cell, human CL0001058
    CSI 45.4
    rCSI 31.7%
    PRS 4.32
  • epithelial cell of lung CL0000082
    CSI 45.02
    rCSI 37.32%
    PRS 3.83
  • CD4-positive helper T cell CL0000492
    CSI 43.83
    rCSI 33.16%
    PRS 5.76
  • group 3 innate lymphoid cell CL0001071
    CSI 43.29
    rCSI 32.53%
    PRS 4.22
  • secretory cell CL0000151
    CSI 42.13
    rCSI 43.96%
    PRS 4.19
  • common dendritic progenitor CL0001029
    CSI 42.09
    rCSI 52.82%
    PRS 5.2
  • pancreatic acinar cell CL0002064
    CSI 41.97
    rCSI 55.78%
    PRS 4.47
  • mucous neck cell CL0000651
    CSI 40
    rCSI 57.66%
    PRS 6.64
  • goblet cell CL0000160
    CSI 38.41
    rCSI 36.29%
    PRS 4.27
  • IgG plasma cell CL0000985
    CSI 38.09
    rCSI 45.63%
    PRS 7.13
  • neural crest cell CL0011012
    CSI 37.84
    rCSI 29.91%
    PRS 2.83
  • keratinocyte CL0000312
    CSI 37.42
    rCSI 31.37%
    PRS 4.92
  • transit amplifying cell CL0009010
    CSI 37.32
    rCSI 57.08%
    PRS 6.7
  • T-helper 17 cell CL0000899
    CSI 37.31
    rCSI 29.62%
    PRS 7.31
  • bronchus fibroblast of lung CL2000093
    CSI 36.97
    rCSI 30.04%
    PRS 4.3
  • pancreatic ductal cell CL0002079
    CSI 35.23
    rCSI 68.51%
    PRS 4.18
  • CD16-negative, CD56-bright natural killer cell, human CL0000938
    CSI 34.65
    rCSI 25.98%
    PRS 12.45
  • Hofbauer cell CL3000001
    CSI 34.2
    rCSI 64.56%
    PRS 5.12
  • epithelial cell CL0000066
    CSI 33.53
    rCSI 51.52%
    PRS 5.91
  • nasal mucosa goblet cell CL0002480
    CSI 33.12
    rCSI 38.41%
    PRS 6.15
  • enterocyte CL0000584
    CSI 32.36
    rCSI 52.19%
    PRS 6.66
  • mesodermal cell CL0000222
    CSI 31.75
    rCSI 38.11%
    PRS 4.09
  • promonocyte CL0000559
    CSI 31.39
    rCSI 53.78%
    PRS 5.48
  • skin fibroblast CL0002620
    CSI 29.72
    rCSI 25.62%
    PRS 6.79
  • luminal epithelial cell of mammary gland CL0002326
    CSI 29.57
    rCSI 53.73%
    PRS 6.27
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 28.98
    rCSI 49.58%
    PRS 8.96
  • paneth cell CL0000510
    CSI 28.61
    rCSI 42.24%
    PRS 6.48
  • intrahepatic cholangiocyte CL0002538
    CSI 28.06
    rCSI 67.32%
    PRS 7.79
  • common lymphoid progenitor CL0000051
    CSI 27.91
    rCSI 37.3%
    PRS 7.86
  • T-helper 1 cell CL0000545
    CSI 27.02
    rCSI 48.77%
    PRS 12.51
  • BEST4+ enteroycte CL4030026
    CSI 26.5
    rCSI 32.96%
    PRS 4.37
  • myeloid leukocyte CL0000766
    CSI 26.1
    rCSI 24.08%
    PRS 4.14
  • myofibroblast cell CL0000186
    CSI 25.12
    rCSI 34.79%
    PRS 5.9
  • respiratory suprabasal cell CL4033048
    CSI 24.94
    rCSI 31.99%
    PRS 4.73
  • tracheal goblet cell CL1000329
    CSI 24.3
    rCSI 53.06%
    PRS 8.4
  • enteroendocrine cell CL0000164
    CSI 23.61
    rCSI 32.27%
    PRS 4.53
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 23.46
    rCSI 24.5%
    PRS 13.27
  • club cell CL0000158
    CSI 23.19
    rCSI 33.98%
    PRS 4.86
  • type B pancreatic cell CL0000169
    CSI 23.06
    rCSI 51.05%
    PRS 3.85
  • type EC enteroendocrine cell CL0000577
    CSI 22.59
    rCSI 80.18%
    PRS 6.75
  • syncytiotrophoblast cell CL0000525
    CSI 22.37
    rCSI 64.44%
    PRS 8.35
  • multi-ciliated epithelial cell CL0005012
    CSI 22.03
    rCSI 21.99%
    PRS 3.46
  • ionocyte CL0005006
    CSI 21.89
    rCSI 23.46%
    PRS 3.78
  • gamma-delta T cell CL0000798
    CSI 21.22
    rCSI 24.92%
    PRS 39.12
  • adventitial cell CL0002503
    CSI 21.09
    rCSI 50.38%
    PRS 6.64
  • forebrain radial glial cell CL0013000
    CSI 20.83
    rCSI 66.84%
    PRS 6.15
  • perivascular cell CL4033054
    CSI 20.82
    rCSI 28.46%
    PRS 4.64
  • microcirculation associated smooth muscle cell CL0008035
    CSI 20.71
    rCSI 59.96%
    PRS 4.64
  • early lymphoid progenitor CL0000936
    CSI 20.58
    rCSI 18.08%
    PRS 4.59
  • respiratory basal cell CL0002633
    CSI 20.13
    rCSI 20.85%
    PRS 4.81
  • type L enteroendocrine cell CL0002279
    CSI 20.01
    rCSI 37.55%
    PRS 8.17
  • foveolar cell of stomach CL0002179
    CSI 19.81
    rCSI 42.17%
    PRS 6.65
  • tendon cell CL0000388
    CSI 19.03
    rCSI 49.46%
    PRS 12.7
  • pancreatic PP cell CL0002275
    CSI 18.87
    rCSI 75.13%
    PRS 7.33
  • activated type II NK T cell CL0000931
    CSI 18.41
    rCSI 20.73%
    PRS 6.86
  • mucosal invariant T cell CL0000940
    CSI 18.13
    rCSI 14.65%
    PRS 10
  • fibroblast of lung CL0002553
    CSI 17.81
    rCSI 16.58%
    PRS 4.08
  • mammary gland epithelial cell CL0002327
    CSI 17.79
    rCSI 62.42%
    PRS 7.44
  • lung ciliated cell CL1000271
    CSI 17.72
    rCSI 20.5%
    PRS 2.97
  • enteric smooth muscle cell CL0002504
    CSI 17.54
    rCSI 25.04%
    PRS 4.66
  • paneth cell of epithelium of small intestine CL1000343
    CSI 17.44
    rCSI 48.88%
    PRS 6.44
  • plasmacytoid dendritic cell CL0000784
    CSI 17.19
    rCSI 17.41%
    PRS 26.78
  • pulmonary alveolar type 2 cell CL0002063
    CSI 17.01
    rCSI 26.38%
    PRS 6.5
  • alveolar adventitial fibroblast CL4028006
    CSI 17
    rCSI 26.85%
    PRS 4.11
  • elicited macrophage CL0000861
    CSI 16.73
    rCSI 15.36%
    PRS 4.69
  • glandular epithelial cell CL0000150
    CSI 16.72
    rCSI 44.03%
    PRS 8
  • lung endothelial cell CL1001567
    CSI 16.7
    rCSI 38.94%
    PRS 10.9
  • antibody secreting cell CL0000946
    CSI 16.61
    rCSI 73.86%
    PRS 19.01
  • colon goblet cell CL0009039
    CSI 16.43
    rCSI 39.05%
    PRS 6.24
  • P/D1 enteroendocrine cell CL0002268
    CSI 16.39
    rCSI 89.23%
    PRS 10.59
  • interstitial cell of Cajal CL0002088
    CSI 16.33
    rCSI 20.79%
    PRS 4.78
  • alveolar type 1 fibroblast cell CL4028004
    CSI 16.26
    rCSI 17.81%
    PRS 4.76
  • pancreatic stellate cell CL0002410
    CSI 16.26
    rCSI 94.6%
    PRS 6.15
  • Kupffer cell CL0000091
    CSI 15.16
    rCSI 34.67%
    PRS 3.98
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 15.01
    rCSI 40.47%
    PRS 5.33
  • endothelial cell of placenta CL0009092
    CSI 15.01
    rCSI 73.98%
    PRS 5.54
  • IgM plasma cell CL0000986
    CSI 15
    rCSI 67.47%
    PRS 22.23
  • lung neuroendocrine cell CL1000223
    CSI 14.68
    rCSI 21.72%
    PRS 4.71
  • astrocyte of the cerebral cortex CL0002605
    CSI -11.5
    rCSI -25.8%
    PRS 2.7%
  • neural progenitor cell CL0011020
    CSI -9.9
    rCSI -43.5%
    PRS 4.2%
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI -9.6
    rCSI -30.2%
    PRS 2.9%
  • GABAergic neuron CL0000617
    CSI -9.4
    rCSI -31.6%
    PRS 3.8%
  • interneuron CL0000099
    CSI -8.7
    rCSI -17.5%
    PRS 3.1%
  • neural cell CL0002319
    CSI -7.9
    rCSI -29.7%
    PRS 8.7%
  • inhibitory interneuron CL0000498
    CSI -7.6
    rCSI -17.6%
    PRS 3.7%
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI -7.2
    rCSI -5.8%
    PRS 7.6%
  • VIP GABAergic cortical interneuron CL4023016
    CSI -6.9
    rCSI -8.3%
    PRS 2.5%
  • regular ventricular cardiac myocyte CL0002131
    CSI -6.8
    rCSI -42.7%
    PRS 3.4%
  • renal interstitial pericyte CL1001318
    CSI -6.6
    rCSI -18.3%
    PRS 4.8%
  • pvalb GABAergic cortical interneuron CL4023018
    CSI -6.5
    rCSI -8.1%
    PRS 2.3%
  • fibroblast of cardiac tissue CL0002548
    CSI -5.6
    rCSI -27.0%
    PRS 2.3%
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI -5.2
    rCSI -12.5%
    PRS 2.5%
  • platelet CL0000233
    CSI -4.6
    rCSI -18.9%
    PRS 12.4%
  • endocardial cell CL0002350
    CSI -4.5
    rCSI -21.6%
    PRS 7.0%
  • exhausted T cell CL0011025
    CSI -4.5
    rCSI -76.1%
    PRS 21.3%
  • cerebellar granule cell CL0001031
    CSI -3.8
    rCSI -5.6%
    PRS 4.2%
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI -3.3
    rCSI -12.4%
    PRS 2.7%
  • tracheobronchial smooth muscle cell CL0019019
    CSI -3.0
    rCSI -5.4%
    PRS 5.5%
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI -2.8
    rCSI -27.3%
    PRS 44.6%
  • double negative thymocyte CL0002489
    CSI -2.2
    rCSI -1.5%
    PRS 4.8%
  • brush cell of tracheobronchial tree CL0002075
    CSI -1.9
    rCSI -5.7%
    PRS 7.0%
  • glutamatergic neuron CL0000679
    CSI -1.8
    rCSI -3.7%
    PRS 4.7%
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI -1.7
    rCSI -6.2%
    PRS 2.2%
  • L6b glutamatergic cortical neuron CL4023038
    CSI -1.5
    rCSI -4.7%
    PRS 2.7%
  • ependymal cell CL0000065
    CSI -1.5
    rCSI -3.0%
    PRS 1.4%
  • lung pericyte CL0009089
    CSI -1.4
    rCSI -3.7%
    PRS 4.9%
  • cord blood hematopoietic stem cell CL2000095
    CSI -1.3
    rCSI -24.4%
    PRS 34.1%
  • lung interstitial macrophage CL4033043
    CSI -1.2
    rCSI -2.7%
    PRS 10.5%
  • forebrain neuroblast CL1000042
    CSI -1.2
    rCSI -13.1%
    PRS 51.9%
  • mononuclear phagocyte CL0000113
    CSI -0.8
    rCSI -1.8%
    PRS 4.5%
  • serous secreting cell CL0000313
    CSI -0.8
    rCSI -3.9%
    PRS 21.1%
  • primordial germ cell CL0000670
    CSI -0.7
    rCSI -3.6%
    PRS 29.9%
  • immature innate lymphoid cell CL0001082
    CSI -0.7
    rCSI -22.4%
    PRS 60.7%
  • hepatic pit cell CL2000054
    CSI -0.7
    rCSI -9.7%
    PRS 42.7%
  • cerebral cortex neuron CL0010012
    CSI -0.6
    rCSI -2.4%
    PRS 5.1%
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI -0.5
    rCSI -1.2%
    PRS 4.9%
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI -0.4
    rCSI -0.7%
    PRS 2.5%
  • endothelial cell of arteriole CL1000412
    CSI -0.3
    rCSI -1.9%
    PRS 20.0%
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI -0.3
    rCSI -1.9%
    PRS 2.8%
  • non-classical monocyte CL0000875
    CSI -0.3
    rCSI -0.5%
    PRS 13.4%
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI -0.2
    rCSI -0.6%
    PRS 6.0%
  • sst GABAergic cortical interneuron CL4023017
    CSI -0.1
    rCSI -0.2%
    PRS 2.6%
  • OFF-bipolar cell CL0000750
    CSI -0.1
    rCSI -0.1%
    PRS 7.2%
  • kidney granular cell CL0000648
    CSI 0.0
    rCSI -0.5%
    PRS 39.3%
  • group 3 innate lymphoid cell, human CL0001078
    CSI 0.0
    rCSI 0.3%
    PRS 64.6%
  • parietal epithelial cell CL1000452
    CSI 0.1
    rCSI 0.1%
    PRS 4.2%
  • melanocyte of skin CL1000458
    CSI 0.1
    rCSI 0.2%
    PRS 2.7%
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 0.2
    rCSI 0.2%
    PRS 3.9%
  • retinal ganglion cell CL0000740
    CSI 0.2
    rCSI 0.4%
    PRS 3.0%
  • double negative T regulatory cell CL0011024
    CSI 0.2
    rCSI 3.9%
    PRS 35.5%
  • basophil CL0000767
    CSI 0.2
    rCSI 0.5%
    PRS 9.1%
  • parietal cell CL0000162
    CSI 0.3
    rCSI 2.4%
    PRS 28.1%
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 0.3
    rCSI 1.6%
    PRS 15.6%
  • cytotoxic T cell CL0000910
    CSI 0.3
    rCSI 1.8%
    PRS 6.4%
  • macula densa epithelial cell CL1000850
    CSI 0.3
    rCSI 4.6%
    PRS 44.9%
  • retinal bipolar neuron CL0000748
    CSI 0.4
    rCSI 0.8%
    PRS 3.2%
  • tissue-resident macrophage CL0000864
    CSI 0.5
    rCSI 2.1%
    PRS 11.5%
  • B-2 B cell CL0000822
    CSI 0.5
    rCSI 10.5%
    PRS 26.5%
  • amacrine cell CL0000561
    CSI 0.6
    rCSI 1.7%
    PRS 3.6%
  • smooth muscle cell of the pulmonary artery CL0002591
    CSI 0.6
    rCSI 4.6%
    PRS 23.5%
  • cardiac muscle cell CL0000746
    CSI 0.6
    rCSI 0.9%
    PRS 3.5%
  • macroglial cell CL0000126
    CSI 0.6
    rCSI 1.5%
    PRS 7.3%
  • hair follicular keratinocyte CL2000092
    CSI 0.6
    rCSI 11.0%
    PRS 17.4%
  • inflammatory macrophage CL0000863
    CSI 0.7
    rCSI 1.2%
    PRS 8.5%
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.7
    rCSI 1.2%
    PRS 2.5%
  • retinal pigment epithelial cell CL0002586
    CSI 0.7
    rCSI 1.4%
    PRS 4.5%
  • kidney epithelial cell CL0002518
    CSI 0.7
    rCSI 1.4%
    PRS 10.1%
  • NKp44-negative group 3 innate lymphoid cell, human CL0001080
    CSI 0.7
    rCSI 22.9%
    PRS 50.3%
  • cone retinal bipolar cell CL0000752
    CSI 0.8
    rCSI 10.7%
    PRS 25.3%
  • Merkel cell CL0000242
    CSI 0.8
    rCSI 19.3%
    PRS 30.3%
  • kidney loop of Henle epithelial cell CL1000909
    CSI 0.9
    rCSI 18.3%
    PRS 35.2%
  • sncg GABAergic cortical interneuron CL4023015
    CSI 0.9
    rCSI 1.4%
    PRS 2.9%
  • pulmonary capillary endothelial cell CL4028001
    CSI 0.9
    rCSI 1.7%
    PRS 6.6%
  • smooth muscle cell of prostate CL1000487
    CSI 0.9
    rCSI 5.5%
    PRS 23.1%
  • paneth cell of colon CL0009009
    CSI 1.0
    rCSI 9.9%
    PRS 12.6%
  • follicular B cell CL0000843
    CSI 1.0
    rCSI 3.7%
    PRS 20.9%
  • Bergmann glial cell CL0000644
    CSI 1.0
    rCSI 1.4%
    PRS 4.5%
  • activated CD4-positive, alpha-beta T cell, human CL0001043
    CSI 1.0
    rCSI 2.5%
    PRS 29.3%
  • microglial cell CL0000129
    CSI 1.1
    rCSI 4.5%
    PRS 18.2%
  • regular atrial cardiac myocyte CL0002129
    CSI 1.2
    rCSI 3.8%
    PRS 4.9%
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.2
    rCSI 3.0%
    PRS 3.3%
  • naive T cell CL0000898
    CSI 1.2
    rCSI 0.9%
    PRS 6.0%
  • follicular dendritic cell CL0000442
    CSI 1.3
    rCSI 20.5%
    PRS 27.3%
  • odontoblast CL0000060
    CSI 1.3
    rCSI 29.6%
    PRS 23.6%
  • erythroblast CL0000765
    CSI 1.4
    rCSI 3.6%
    PRS 7.0%
  • endothelial cell of vascular tree CL0002139
    CSI 1.4
    rCSI 7.5%
    PRS 10.5%
  • neuroplacodal cell CL0000032
    CSI 1.4
    rCSI 13.0%
    PRS 15.9%
  • blood vessel smooth muscle cell CL0019018
    CSI 1.5
    rCSI 11.9%
    PRS 4.4%
  • skeletal muscle satellite stem cell CL0008011
    CSI 1.5
    rCSI 6.7%
    PRS 16.6%
  • midbrain dopaminergic neuron CL2000097
    CSI 1.5
    rCSI 9.7%
    PRS 7.3%
  • epithelial cell of nephron CL1000449
    CSI 1.6
    rCSI 14.7%
    PRS 18.5%
  • vasa recta descending limb cell CL1001285
    CSI 1.6
    rCSI 12.6%
    PRS 18.7%
  • decidual natural killer cell, human CL0002343
    CSI 1.6
    rCSI 16.6%
    PRS 37.4%
  • hepatocyte CL0000182
    CSI 1.6
    rCSI 2.9%
    PRS 4.0%
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 1.7
    rCSI 2.7%
    PRS 10.5%
  • glial cell CL0000125
    CSI 1.7
    rCSI 6.6%
    PRS 4.5%
  • erythrocyte CL0000232
    CSI 1.8
    rCSI 4.0%
    PRS 5.9%
  • brush cell CL0002204
    CSI 1.8
    rCSI 3.5%
    PRS 12.0%

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 [HSPA5](/details-gene/3309), also known as Binding Immunoglobulin Protein (BiP) or Glucose-Regulated Protein 78 (GRP78), is a central molecular chaperone of the Hsp70 family located in the endoplasmic reticulum (ER). It plays a critical role in protein folding and quality control, ensuring the proper conformation of nascent polypeptides and preventing the aggregation of misfolded proteins. [HSPA5](/details-gene/3309) is a master regulator of the Unfolded Protein Response (UPR), a cellular stress response pathway activated by the accumulation of unfolded proteins in the ER. Its expression is particularly high in professional secretory cells, such as [plasmablasts](/details-cell/CL0000980), and in progenitor cells undergoing differentiation, reflecting its essential function in managing high protein synthesis and secretion loads. Clinically, it is associated with certain developmental and autoimmune conditions ([138120](https://omim.org/entry/138120)) and is a key factor in cancer cell survival. ## Cellular Roles and Expression Landscape The expression profile of [HSPA5](/details-gene/3309) highlights its fundamental role in cellular homeostasis, particularly in cells with a high capacity for protein synthesis and secretion. **Overall**, the gene shows the highest significance in professional secretory cells and highly active progenitor cells. It is a top marker for [plasmablasts](/details-cell/CL0000980) (CSI: 119.44), the terminally differentiated B-lymphocytes responsible for massive antibody production. This is consistent with its role in folding and assembling immunoglobulin chains in the ER. High significance is also observed in various hematopoietic progenitors, including [granulocyte monocyte progenitor cells](/details-cell/CL0000557), [common myeloid progenitors](/details-cell/CL0000049), [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050), and [hematopoietic stem cells](/details-cell/CL0000037), suggesting its importance in managing the proteomic changes required for lineage commitment and differentiation. Furthermore, high expression in secretory epithelial cells, such as those in the [fallopian tube](/details-cell/CL4030006) and [colon](/details-cell/CL0011108), as well as in hormone-producing [pancreatic A](/details-cell/CL0000171) and [D cells](/details-cell/CL0000173), reinforces its function in supporting a heavy secretory workload. Conversely, [HSPA5](/details-gene/3309) shows very low significance in terminally differentiated cells with more stable proteomes. Its expression is notably low across various neuronal subtypes, including [GABAergic neurons](/details-cell/CL0000617), [interneurons](/details-cell/CL0000099), and [astrocytes of the cerebral cortex](/details-cell/CL0002605). Similarly, it shows low significance in [regular ventricular cardiac myocytes](/details-cell/CL0002131). This restricted expression pattern suggests a specialized role in dynamic cellular processes rather than in the general maintenance of quiescent, terminally differentiated tissues. ## Pathways and Molecular Function The functional annotations for [HSPA5](/details-gene/3309) confirm its identity as a master regulator of ER proteostasis. It is a key component of the '[Endoplasmic reticulum unfolded protein response](/details-go/GO:0030968)' ([GO:0030968](https://www.ebi.ac.uk/QuickGO/term/GO:0030968)) and the broader '[Response to endoplasmic reticulum stress](/details-go/GO:0034976)' ([GO:0034976](https://www.ebi.ac.uk/QuickGO/term/GO:0034976)). Reactome pathways further detail its involvement in all three branches of the UPR, including '[Atf6 (atf6-alpha) activates chaperone genes](/details-pathway/R-HSA-381183)', '[Ire1alpha activates chaperones](/details-pathway/R-HSA-381070)', and '[Perk regulates gene expression](/details-pathway/R-HSA-381042)'. These functions are driven by its core molecular activities, which include '[ATP binding](/details-go/GO:0005524)' ([GO:0005524](https://www.ebi.ac.uk/QuickGO/term/GO:0005524)), '[Unfolded protein binding](/details-go/GO:0051082)' ([GO:0051082](https://www.ebi.ac.uk/QuickGO/term/GO:0051082)), and being an '[Atp-dependent protein folding chaperone](/details-go/GO:0140662)' ([GO:0140662](https://www.ebi.ac.uk/QuickGO/term/GO:0140662)). Consistent with its high expression in immune cells, [HSPA5](/details-gene/3309) is integral to the '[Immune system](/details-pathway/R-HSA-168256)' ([R-HSA-168256](https://reactome.org/content/detail/R-HSA-168256)), particularly in the '[Class i mhc mediated antigen processing & presentation](/details-pathway/R-HSA-983169)' pathway ([R-HSA-983169](https://reactome.org/content/detail/R-HSA-983169)). This highlights its role in folding MHC molecules and loading them with peptides for presentation to T cells. Its anti-apoptotic function ('[Negative regulation of apoptotic process](/details-go/GO:0043066)' ([GO:0043066](https://www.ebi.ac.uk/QuickGO/term/GO:0043066))) is crucial for cell survival under stress, a mechanism often co-opted by cancer cells. ## Research Directions The central role of [HSPA5](/details-gene/3309) in managing proteotoxic stress positions it as a critical node in both normal physiology and disease. Future research should focus on dissecting its context-specific functions and therapeutic potential. **Testable Hypotheses:** 1. Given its supreme significance in [plasmablasts](/details-cell/CL0000980) and its role in the UPR, it is hypothesized that the demand for massive immunoglobulin synthesis during plasma cell differentiation creates a state of chronic, low-level ER stress that makes these cells uniquely dependent on [HSPA5](/details-gene/3309) for survival and function. 2. Based on reports that [HSPA5](/details-gene/3309) can be expressed on the cell surface under stress and act as an autoantigen ([Link](https://doi.org/10.4049/jimmunol.166.3.1492)), it is hypothesized that in diseases like rheumatoid arthritis, surface-exposed [HSPA5](/details-gene/3309) on stressed synovial cells functions as a damage-associated molecular pattern (DAMP) that perpetuates autoimmune inflammation by activating autoreactive B and T cells. 3. The high expression of [HSPA5](/details-gene/3309) in multiple hematopoietic progenitor populations suggests that it is a key regulator of lineage commitment. It is hypothesized that the downregulation of [HSPA5](/details-gene/3309) impairs the differentiation of specific lineages, such as the myeloid or erythroid lineages, by inducing unresolved ER stress and apoptosis in progenitor cells. **Proposed Experiment:** To test hypothesis 1, the dependence of plasma cells on [HSPA5](/details-gene/3309), primary human B cells could be stimulated *in vitro* to differentiate into [plasmablasts](/details-cell/CL0000980). These differentiating cultures would be treated with a specific small-molecule inhibitor of the [HSPA5](/details-gene/3309) ATPase activity. The experimental readouts would include: (i) quantification of immunoglobulin secretion via ELISA to assess secretory function; (ii) flow cytometry analysis of plasma cell markers (CD27, CD38) to measure differentiation efficiency; and (iii) Western blot analysis for UPR markers (e.g., CHOP, spliced XBP1) and apoptosis markers (cleaved Caspase-3) to determine the effect of [HSPA5](/details-gene/3309) inhibition on cellular stress and viability. **Therapeutic Potential:** [HSPA5](/details-gene/3309) is a compelling therapeutic target, primarily for **inhibition**. Many cancers, particularly secretory cancers like multiple myeloma (a malignancy of plasma cells), are highly dependent on [HSPA5](/details-gene/3309) to manage the oncogenic burden of high protein production and ER stress. Inhibiting [HSPA5](/details-gene/3309) could selectively kill these malignant cells or sensitize them to conventional proteasome inhibitors or chemotherapy. Its stress-induced cell surface expression also presents an opportunity for targeted therapies, such as antibody-drug conjugates (ADCs) or CAR-T cells directed against tumors that display surface [HSPA5](/details-gene/3309), potentially offering a favorable therapeutic window.

Genular Protein ID: 972276839

Symbol: BIP_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 2840249

Title: Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation.

PubMed ID: 2840249

DOI: 10.1089/dna.1988.7.275

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 1480470

Title: A direct-repeat sequence of the human BiP gene is required for A23187-mediated inducibility and an inducible nuclear factor binding.

PubMed ID: 1480470

DOI: 10.1093/nar/20.24.6481

PubMed ID: 11160188

Title: The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis.

PubMed ID: 11160188

DOI: 10.4049/jimmunol.166.3.1492

PubMed ID: 9150946

Title: Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2.

PubMed ID: 9150946

DOI: 10.1002/elps.1150180342

PubMed ID: 2294010

Title: Heat shock proteins bind calcitonin.

PubMed ID: 2294010

DOI: 10.1210/endo-126-1-672

PubMed ID: 9150948

Title: A two-dimensional gel database of human colon carcinoma proteins.

PubMed ID: 9150948

DOI: 10.1002/elps.1150180344

PubMed ID: 1550958

Title: Analysis in vivo of GRP78-BiP/substrate interactions and their role in induction of the GRP78-BiP gene.

PubMed ID: 1550958

DOI: 10.1091/mbc.3.2.143

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: 21289099

Title: Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells.

PubMed ID: 21289099

DOI: 10.1091/mbc.e10-08-0724

PubMed ID: 23349634

Title: A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.

PubMed ID: 23349634

DOI: 10.1371/journal.pgen.1003210

PubMed ID: 12475965

Title: A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins.

PubMed ID: 12475965

DOI: 10.1091/mbc.e02-05-0311

PubMed ID: 12699405

Title: Association of stress proteins with autoantigens: a possible mechanism for triggering autoimmunity?

PubMed ID: 12699405

DOI: 10.1046/j.1365-2249.2003.02153.x

PubMed ID: 12411443

Title: ERdj5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress.

PubMed ID: 12411443

DOI: 10.1074/jbc.m206995200

PubMed ID: 12643545

Title: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.

PubMed ID: 12643545

DOI: 10.1021/pr025562r

PubMed ID: 15098107

Title: Identification of GRP 78 (BiP) as a liver cell expressed receptor element for dengue virus serotype 2.

PubMed ID: 15098107

DOI: 10.1007/s00705-003-0263-x

PubMed ID: 18621045

Title: Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na+, K+ ATPase complex.

PubMed ID: 18621045

DOI: 10.1016/j.yexcr.2008.06.016

PubMed ID: 17081065

Title: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

PubMed ID: 17081065

DOI: 10.1021/pr060363j

PubMed ID: 18502753

Title: Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP.

PubMed ID: 18502753

DOI: 10.1074/jbc.m709336200

PubMed ID: 18264092

Title: OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD.

PubMed ID: 18264092

DOI: 10.1038/ncb1689

PubMed ID: 19538957

Title: Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins.

PubMed ID: 19538957

DOI: 10.1016/j.yexcr.2009.06.009

PubMed ID: 20484814

Title: The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice.

PubMed ID: 20484814

DOI: 10.1172/jci42164

PubMed ID: 21080038

Title: The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone.

PubMed ID: 21080038

DOI: 10.1007/s11010-010-0635-y

PubMed ID: 22637475

Title: Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion.

PubMed ID: 22637475

DOI: 10.1074/jbc.m112.356345

PubMed ID: 22905912

Title: Resveratrol-induced changes of the human adipocyte secretion profile.

PubMed ID: 22905912

DOI: 10.1021/pr300539b

PubMed ID: 23921388

Title: Identification and characterization of a novel human methyltransferase modulating Hsp70 function through lysine methylation.

PubMed ID: 23921388

DOI: 10.1074/jbc.m113.483248

PubMed ID: 23990668

Title: Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in cancer cell migration.

PubMed ID: 23990668

DOI: 10.1093/jnci/djt224

PubMed ID: 23769672

Title: ERdj5 is the ER reductase that catalyzes the removal of non-native disulfides and correct folding of the LDL receptor.

PubMed ID: 23769672

DOI: 10.1016/j.molcel.2013.05.014

PubMed ID: 22689054

Title: GRP78 regulates clusterin stability, retrotranslocation and mitochondrial localization under ER stress in prostate cancer.

PubMed ID: 22689054

DOI: 10.1038/onc.2012.212

PubMed ID: 24355926

Title: CotH3 mediates fungal invasion of host cells during mucormycosis.

PubMed ID: 24355926

DOI: 10.1172/jci71349

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 24129315

Title: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.

PubMed ID: 24129315

DOI: 10.1074/mcp.o113.027870

PubMed ID: 25218447

Title: Uncovering global SUMOylation signaling networks in a site-specific manner.

PubMed ID: 25218447

DOI: 10.1038/nsmb.2890

PubMed ID: 25114211

Title: Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.

PubMed ID: 25114211

DOI: 10.1073/pnas.1413825111

PubMed ID: 26045166

Title: KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78.

PubMed ID: 26045166

DOI: 10.1158/0008-5472.can-14-3751

PubMed ID: 25601083

Title: A novel link between Fic (filamentation induced by cAMP)-mediated adenylylation/AMPylation and the unfolded protein response.

PubMed ID: 25601083

DOI: 10.1074/jbc.m114.618348

PubMed ID: 25755297

Title: System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.

PubMed ID: 25755297

DOI: 10.1074/mcp.o114.044792

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 26657846

Title: Versatile function of the circadian protein CIPC as a regulator of Erk activation.

PubMed ID: 26657846

DOI: 10.1016/j.bbrc.2015.11.117

PubMed ID: 26940976

Title: Glucose-regulated protein 78 (GRP78) binds directly to PIP3 phosphatase SKIP and determines its localization.

PubMed ID: 26940976

DOI: 10.1111/gtc.12353

PubMed ID: 27159390

Title: Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis.

PubMed ID: 27159390

DOI: 10.1172/jci82744

PubMed ID: 28286085

Title: HSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum.

PubMed ID: 28286085

DOI: 10.1016/j.gene.2017.03.005

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 28332555

Title: LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway.

PubMed ID: 28332555

DOI: 10.1038/srep44988

PubMed ID: 28053106

Title: GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed ID: 28053106

DOI: 10.1128/jvi.02274-16

PubMed ID: 29719251

Title: Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier.

PubMed ID: 29719251

DOI: 10.1016/j.celrep.2018.03.122

PubMed ID: 29497057

Title: Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.

PubMed ID: 29497057

DOI: 10.1038/s41467-018-03355-0

PubMed ID: 32487760

Title: GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis.

PubMed ID: 32487760

DOI: 10.1128/mbio.01087-20

PubMed ID: 33432092

Title: A functional interaction between GRP78 and Zika virus E protein.

PubMed ID: 33432092

DOI: 10.1038/s41598-020-79803-z

PubMed ID: 20072699

Title: Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78.

PubMed ID: 20072699

DOI: 10.1371/journal.pone.0008625

PubMed ID: 21526763

Title: Adenosine-derived inhibitors of 78 kDa glucose regulated protein (Grp78) ATPase: insights into isoform selectivity.

PubMed ID: 21526763

DOI: 10.1021/jm101625x

PubMed ID: 26655470

Title: Close and allosteric opening of the polypeptide-binding site in a human Hsp70 chaperone BiP.

PubMed ID: 26655470

DOI: 10.1016/j.str.2015.10.012

Sequence Information:

  • Length: 654
  • Mass: 72333
  • Checksum: 59B7D8D85BC32A00
  • Sequence:
  • MKLSLVAAML LLLSAARAEE EDKKEDVGTV VGIDLGTTYS CVGVFKNGRV EIIANDQGNR 
    ITPSYVAFTP EGERLIGDAA KNQLTSNPEN TVFDAKRLIG RTWNDPSVQQ DIKFLPFKVV 
    EKKTKPYIQV DIGGGQTKTF APEEISAMVL TKMKETAEAY LGKKVTHAVV TVPAYFNDAQ 
    RQATKDAGTI AGLNVMRIIN EPTAAAIAYG LDKREGEKNI LVFDLGGGTF DVSLLTIDNG 
    VFEVVATNGD THLGGEDFDQ RVMEHFIKLY KKKTGKDVRK DNRAVQKLRR EVEKAKRALS 
    SQHQARIEIE SFYEGEDFSE TLTRAKFEEL NMDLFRSTMK PVQKVLEDSD LKKSDIDEIV 
    LVGGSTRIPK IQQLVKEFFN GKEPSRGINP DEAVAYGAAV QAGVLSGDQD TGDLVLLDVC 
    PLTLGIETVG GVMTKLIPRN TVVPTKKSQI FSTASDNQPT VTIKVYEGER PLTKDNHLLG 
    TFDLTGIPPA PRGVPQIEVT FEIDVNGILR VTAEDKGTGN KNKITITNDQ NRLTPEEIER 
    MVNDAEKFAE EDKKLKERID TRNELESYAY SLKNQIGDKE KLGGKLSSED KETMEKAVEE 
    KIEWLESHQD ADIEDFKAKK KELEEIVQPI ISKLYGSAGP PPTGEEDTAE KDEL