CSTB | ENSG00000160213 | NCBI 1476

Details for: CSTB

Gene ID: 1476

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: CSTB

Ensembl ID: ENSG00000160213

Description: cystatin B

Cell Significance Landscape

Display Count:

Associated with

Immune system
(R-HSA-168256)
Innate immune system
(R-HSA-168249)
Neutrophil degranulation
(R-HSA-6798695)
Adult locomotory behavior
(GO:0008344)
Collagen-containing extracellular matrix
(GO:0062023)
Cysteine-type endopeptidase inhibitor activity
(GO:0004869)
Cytoplasm
(GO:0005737)
Cytosol
(GO:0005829)
Endopeptidase inhibitor activity
(GO:0004866)
Extracellular exosome
(GO:0070062)
Extracellular region
(GO:0005576)
Extracellular space
(GO:0005615)
Ficolin-1-rich granule lumen
(GO:1904813)
Negative regulation of peptidase activity
(GO:0010466)
Negative regulation of proteolysis
(GO:0045861)
Nucleolus
(GO:0005730)
Nucleus
(GO:0005634)
Protease binding
(GO:0002020)
Rna binding
(GO:0003723)
Secretory granule lumen
(GO:0034774)
Tertiary granule lumen
(GO:1904724)

Significant Cells

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

elicited macrophage CL0000861

CSI 117.87

rCSI 100%

PRS 5.28
CD14-low, CD16-positive monocyte CL0002396

CSI 91.45

rCSI 70.46%

PRS 4.18
ciliated epithelial cell CL0000067

CSI 90.49

rCSI 79.58%

PRS 3.34
epithelial cell of lower respiratory tract CL0002632

CSI 86.67

rCSI 67.19%

PRS 4.4
colon epithelial cell CL0011108

CSI 83.29

rCSI 87.25%

PRS 4.31
multi-ciliated epithelial cell CL0005012

CSI 82.78

rCSI 82.62%

PRS 3.95
nasal mucosa goblet cell CL0002480

CSI 79.91

rCSI 92.67%

PRS 6.94
fallopian tube secretory epithelial cell CL4030006

CSI 79.15

rCSI 76.19%

PRS 4.78
epithelial cell of lung CL0000082

CSI 75.41

rCSI 62.51%

PRS 4.37
keratinocyte CL0000312

CSI 74.55

rCSI 62.5%

PRS 5.56
lung ciliated cell CL1000271

CSI 74.32

rCSI 85.94%

PRS 3.36
intestinal epithelial cell CL0002563

CSI 73.07

rCSI 76.37%

PRS 4.91
myeloid leukocyte CL0000766

CSI 70.75

rCSI 65.27%

PRS 4.68
extravillous trophoblast CL0008036

CSI 68.19

rCSI 84.35%

PRS 4.05
alternatively activated macrophage CL0000890

CSI 64

rCSI 80.47%

PRS 7.12
respiratory suprabasal cell CL4033048

CSI 63.62

rCSI 81.6%

PRS 5.34
stem cell CL0000034

CSI 63.03

rCSI 60.77%

PRS 2.47
intestine goblet cell CL0019031

CSI 62.95

rCSI 55.88%

PRS 4.63
pulmonary ionocyte CL0017000

CSI 61.97

rCSI 75.44%

PRS 5.85
pancreatic A cell CL0000171

CSI 60.48

rCSI 63.36%

PRS 4.95
secretory cell CL0000151

CSI 56.68

rCSI 59.14%

PRS 4.73
pancreatic D cell CL0000173

CSI 54.27

rCSI 53.37%

PRS 5.06
alveolar macrophage CL0000583

CSI 53.23

rCSI 87.68%

PRS 5.41
club cell CL0000158

CSI 52

rCSI 76.16%

PRS 5.49
respiratory basal cell CL0002633

CSI 51.69

rCSI 53.54%

PRS 5.43
Hofbauer cell CL3000001

CSI 51.31

rCSI 96.87%

PRS 5.77
CD1c-positive myeloid dendritic cell CL0002399

CSI 50.88

rCSI 61.46%

PRS 5.42
pulmonary alveolar type 2 cell CL0002063

CSI 49.78

rCSI 77.22%

PRS 7.43
respiratory hillock cell CL4030023

CSI 49.73

rCSI 88.68%

PRS 8.03
mucous neck cell CL0000651

CSI 49.67

rCSI 71.59%

PRS 7.5
tracheal goblet cell CL1000329

CSI 49.46

rCSI 100%

PRS 9.49
M cell of gut CL0000682

CSI 49.21

rCSI 52.29%

PRS 8.29
conventional dendritic cell CL0000990

CSI 48.26

rCSI 40.29%

PRS 15.17
enterocyte CL0000584

CSI 47.26

rCSI 76.2%

PRS 7.52
CD14-positive, CD16-positive monocyte CL0002397

CSI 44.8

rCSI 58.7%

PRS 6.48
promonocyte CL0000559

CSI 44.66

rCSI 76.52%

PRS 6.19
conjunctival epithelial cell CL1000432

CSI 44.63

rCSI 68.16%

PRS 4.62
placental villous trophoblast CL2000060

CSI 41.86

rCSI 64.68%

PRS 4.34
epithelial cell CL0000066

CSI 41.5

rCSI 63.76%

PRS 6.68
duct epithelial cell CL0000068

CSI 41.16

rCSI 60.22%

PRS 4.89
non-classical monocyte CL0000875

CSI 41.06

rCSI 65.81%

PRS 15.36
ciliated columnar cell of tracheobronchial tree CL0002145

CSI 40.74

rCSI 92.87%

PRS 4.87
ciliated cell CL0000064

CSI 40.31

rCSI 65.32%

PRS 4.7
transit amplifying cell of colon CL0009011

CSI 40.19

rCSI 47.21%

PRS 5.61
foveolar cell of stomach CL0002179

CSI 39.62

rCSI 84.34%

PRS 7.52
acinar cell CL0000622

CSI 39.44

rCSI 57.84%

PRS 6.08
colonocyte CL1000347

CSI 37.49

rCSI 53.74%

PRS 6.47
type B pancreatic cell CL0000169

CSI 36.45

rCSI 80.7%

PRS 4.33
pancreatic ductal cell CL0002079

CSI 33.61

rCSI 65.37%

PRS 4.72
goblet cell CL0000160

CSI 32.31

rCSI 30.54%

PRS 4.83
kidney epithelial cell CL0002518

CSI 31.43

rCSI 59.99%

PRS 11.37
lung macrophage CL1001603

CSI 30.9

rCSI 69.02%

PRS 5.23
squamous epithelial cell CL0000076

CSI 30.25

rCSI 71.81%

PRS 6.21
transit amplifying cell CL0009010

CSI 30.03

rCSI 45.93%

PRS 7.57
lung interstitial macrophage CL4033043

CSI 30

rCSI 67.34%

PRS 11.66
hematopoietic stem cell CL0000037

CSI 28.57

rCSI 18.99%

PRS 5.52
melanocyte CL0000148

CSI 28.41

rCSI 21.04%

PRS 4.34
dendritic cell CL0000451

CSI 28.05

rCSI 34.57%

PRS 15.62
dendritic cell, human CL0001056

CSI 27.74

rCSI 42.6%

PRS 5.37
intestinal tuft cell CL0019032

CSI 27.07

rCSI 41.36%

PRS 5.35
enteroendocrine cell CL0000164

CSI 26.74

rCSI 36.53%

PRS 5.11
plasmablast CL0000980

CSI 26.16

rCSI 20.58%

PRS 5.51
deuterosomal cell CL4033044

CSI 25.9

rCSI 87.55%

PRS 7.98
ionocyte CL0005006

CSI 25.8

rCSI 27.65%

PRS 4.27
renal alpha-intercalated cell CL0005011

CSI 25.49

rCSI 34.08%

PRS 6.3
luminal epithelial cell of mammary gland CL0002326

CSI 25.48

rCSI 46.3%

PRS 7.08
promyelocyte CL0000836

CSI 25.41

rCSI 36.64%

PRS 6.44
bronchus fibroblast of lung CL2000093

CSI 25.12

rCSI 20.41%

PRS 4.91
bronchial goblet cell CL1000312

CSI 25.02

rCSI 100%

PRS 10.31
classical monocyte CL0000860

CSI 24.9

rCSI 36.91%

PRS 46.42
fraction A pre-pro B cell CL0002045

CSI 24.22

rCSI 27.73%

PRS 9.63
Mueller cell CL0000636

CSI 23.73

rCSI 54.17%

PRS 4.29
Langerhans cell CL0000453

CSI 22.86

rCSI 34.91%

PRS 8.13
common dendritic progenitor CL0001029

CSI 22.8

rCSI 28.62%

PRS 5.87
Kupffer cell CL0000091

CSI 22.51

rCSI 51.47%

PRS 4.49
peripheral nervous system neuron CL2000032

CSI 22.34

rCSI 30.43%

PRS 4.19
macrophage CL0000235

CSI 22.13

rCSI 40.25%

PRS 22.42
hepatocyte CL0000182

CSI 22.01

rCSI 39.4%

PRS 4.46
kidney loop of Henle thin ascending limb epithelial cell CL1001107

CSI 21.5

rCSI 55.59%

PRS 4.37
CD16-positive, CD56-dim natural killer cell, human CL0000939

CSI 21.43

rCSI 14.28%

PRS 13.02
glandular epithelial cell CL0000150

CSI 21.07

rCSI 55.48%

PRS 9.05
adventitial cell CL0002503

CSI 21.02

rCSI 50.19%

PRS 7.48
mammary gland epithelial cell CL0002327

CSI 20.94

rCSI 73.46%

PRS 8.42
colon goblet cell CL0009039

CSI 20.15

rCSI 47.91%

PRS 7.05
central memory CD8-positive, alpha-beta T cell CL0000907

CSI 19.88

rCSI 13.4%

PRS 5.62
intrahepatic cholangiocyte CL0002538

CSI 19.61

rCSI 47.05%

PRS 8.81
CD14-positive monocyte CL0001054

CSI 19.57

rCSI 24.37%

PRS 6.79
granulocyte monocyte progenitor cell CL0000557

CSI 19.18

rCSI 16.61%

PRS 5.14
megakaryocyte-erythroid progenitor cell CL0000050

CSI 19.01

rCSI 17.17%

PRS 4.08
keratocyte CL0002363

CSI 18.81

rCSI 45.21%

PRS 7.22
intermediate monocyte CL0002393

CSI 18.8

rCSI 28.37%

PRS 4.54
monocyte CL0000576

CSI 18.37

rCSI 33.21%

PRS 13.27
forebrain radial glial cell CL0013000

CSI 18.27

rCSI 58.61%

PRS 6.99
common myeloid progenitor CL0000049

CSI 17.94

rCSI 14.5%

PRS 4.54
type EC enteroendocrine cell CL0000577

CSI 17.73

rCSI 62.95%

PRS 7.63
mucus secreting cell CL0000319

CSI 16.71

rCSI 26.54%

PRS 6.03
fibroblast of lung CL0002553

CSI 16.35

rCSI 15.21%

PRS 4.66
retinal pigment epithelial cell CL0002586

CSI 16.34

rCSI 32.45%

PRS 5.1
stromal cell of ovary CL0002132

CSI 16.25

rCSI 44.64%

PRS 7.75
alveolar adventitial fibroblast CL4028006

CSI 16.12

rCSI 25.46%

PRS 4.63

adipocyte CL0000136

CSI -13.1

rCSI -16.8%

PRS 5.7%
CD8-positive, alpha-beta cytotoxic T cell CL0000794

CSI -10.8

rCSI -12.9%

PRS 8.1%
pulmonary capillary endothelial cell CL4028001

CSI -10.6

rCSI -20.3%

PRS 7.4%
retinal bipolar neuron CL0000748

CSI -10.4

rCSI -19.5%

PRS 3.6%
alveolar type 1 fibroblast cell CL4028004

CSI -9.6

rCSI -10.5%

PRS 5.4%
regular ventricular cardiac myocyte CL0002131

CSI -8.8

rCSI -55.0%

PRS 3.8%
vascular associated smooth muscle cell CL0000359

CSI -5.9

rCSI -19.1%

PRS 5.7%
cerebellar granule cell CL0001031

CSI -5.8

rCSI -8.5%

PRS 4.7%
interneuron CL0000099

CSI -5.6

rCSI -11.2%

PRS 3.5%
Schwann cell CL0002573

CSI -5.5

rCSI -15.6%

PRS 6.3%
CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792

CSI -5.3

rCSI -5.2%

PRS 7.4%
chandelier pvalb GABAergic cortical interneuron CL4023036

CSI -4.9

rCSI -15.2%

PRS 3.2%
basal cell of epidermis CL0002187

CSI -4.4

rCSI -7.8%

PRS 6.3%
midzonal region hepatocyte CL0019028

CSI -3.9

rCSI -9.2%

PRS 8.1%
primordial germ cell CL0000670

CSI -3.4

rCSI -16.8%

PRS 33.3%
sncg GABAergic cortical interneuron CL4023015

CSI -3.2

rCSI -5.1%

PRS 3.2%
lung resident memory CD8-positive, alpha-beta T cell CL4033039

CSI -2.5

rCSI -6.5%

PRS 16.4%
hepatic stellate cell CL0000632

CSI -2.3

rCSI -8.7%

PRS 4.0%
corticothalamic-projecting glutamatergic cortical neuron CL4023013

CSI -1.9

rCSI -11.3%

PRS 3.0%
L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041

CSI -1.9

rCSI -6.8%

PRS 2.5%
alpha-beta T cell CL0000789

CSI -1.8

rCSI -2.1%

PRS 7.5%
cerebral cortex neuron CL0010012

CSI -1.4

rCSI -5.6%

PRS 5.6%
inhibitory interneuron CL0000498

CSI -1.1

rCSI -2.5%

PRS 4.2%
lung pericyte CL0009089

CSI -1.1

rCSI -2.9%

PRS 5.5%
effector memory CD8-positive, alpha-beta T cell CL0000913

CSI -1.1

rCSI -1.0%

PRS 7.3%
effector CD4-positive, alpha-beta T cell CL0001044

CSI -0.9

rCSI -2.6%

PRS 6.7%
exhausted T cell CL0011025

CSI -0.9

rCSI -14.6%

PRS 23.8%
astrocyte of the cerebral cortex CL0002605

CSI -0.7

rCSI -1.6%

PRS 2.9%
lamp5 GABAergic cortical interneuron CL4023011

CSI -0.6

rCSI -1.0%

PRS 2.8%
microglial cell CL0000129

CSI -0.5

rCSI -2.0%

PRS 19.9%
naive T cell CL0000898

CSI -0.5

rCSI -0.3%

PRS 6.7%
smooth muscle cell of prostate CL1000487

CSI -0.3

rCSI -2.0%

PRS 25.7%
cord blood hematopoietic stem cell CL2000095

CSI -0.3

rCSI -6.1%

PRS 37.7%
decidual natural killer cell, human CL0002343

CSI -0.3

rCSI -2.6%

PRS 41.4%
class switched memory B cell CL0000972

CSI -0.2

rCSI -0.1%

PRS 7.9%
GABAergic amacrine cell CL4030027

CSI 0.1

rCSI 0.3%

PRS 5.6%
L6b glutamatergic cortical neuron CL4023038

CSI 0.1

rCSI 0.4%

PRS 3.0%
megakaryocyte progenitor cell CL0000553

CSI 0.2

rCSI 3.5%

PRS 11.3%
eye photoreceptor cell CL0000287

CSI 0.2

rCSI 2.3%

PRS 16.1%
near-projecting glutamatergic cortical neuron CL4023012

CSI 0.3

rCSI 1.1%

PRS 2.9%
blood vessel smooth muscle cell CL0019018

CSI 0.3

rCSI 2.8%

PRS 4.9%
neural progenitor cell CL0011020

CSI 0.4

rCSI 1.7%

PRS 4.7%
antibody secreting cell CL0000946

CSI 0.5

rCSI 2.2%

PRS 21.5%
CD34-positive, CD56-positive, CD117-positive common innate lymphoid precursor, human CL0001074

CSI 0.6

rCSI 7.0%

PRS 20.3%
basophil mast progenitor cell CL0002028

CSI 0.7

rCSI 3.5%

PRS 14.8%
sst GABAergic cortical interneuron CL4023017

CSI 0.7

rCSI 0.9%

PRS 3.0%
renal intercalated cell CL0005010

CSI 0.7

rCSI 6.3%

PRS 40.1%
OFF midget ganglion cell CL4033047

CSI 0.7

rCSI 14.7%

PRS 5.0%
glioblast CL0000030

CSI 0.7

rCSI 1.2%

PRS 4.0%
transitional stage B cell CL0000818

CSI 0.8

rCSI 2.5%

PRS 14.5%
parietal cell CL0000162

CSI 0.8

rCSI 6.8%

PRS 31.8%
collagen secreting cell CL0000667

CSI 0.8

rCSI 4.6%

PRS 24.6%
ON parasol ganglion cell CL4033052

CSI 0.8

rCSI 11.6%

PRS 3.6%
cytotoxic T cell CL0000910

CSI 0.9

rCSI 5.2%

PRS 7.3%
ON midget ganglion cell CL4033046

CSI 0.9

rCSI 18.6%

PRS 4.6%
epicardial adipocyte CL1000309

CSI 0.9

rCSI 3.1%

PRS 7.3%
tracheobronchial goblet cell CL0019003

CSI 0.9

rCSI 15.2%

PRS 67.7%
serous secreting cell of bronchus submucosal gland CL4033005

CSI 1.0

rCSI 5.5%

PRS 25.2%
small intestine goblet cell CL1000495

CSI 1.0

rCSI 2.2%

PRS 6.4%
tuft cell of colon CL0009041

CSI 1.0

rCSI 2.4%

PRS 11.3%
follicular dendritic cell CL0000442

CSI 1.0

rCSI 16.7%

PRS 30.5%
vasa recta ascending limb cell CL1001131

CSI 1.1

rCSI 4.8%

PRS 21.5%
tissue-resident macrophage CL0000864

CSI 1.1

rCSI 5.0%

PRS 12.9%
kidney resident macrophage CL1000698

CSI 1.1

rCSI 22.5%

PRS 71.7%
activated CD4-positive, alpha-beta T cell, human CL0001043

CSI 1.1

rCSI 2.7%

PRS 32.5%
mesenchymal lymphangioblast CL0005021

CSI 1.3

rCSI 33.5%

PRS 25.7%
kidney distal convoluted tubule epithelial cell CL1000849

CSI 1.3

rCSI 13.9%

PRS 7.7%
late pro-B cell CL0002048

CSI 1.3

rCSI 3.3%

PRS 15.5%
odontoblast CL0000060

CSI 1.5

rCSI 33.3%

PRS 26.6%
mature alpha-beta T cell CL0000791

CSI 1.5

rCSI 5.6%

PRS 8.1%
L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040

CSI 1.5

rCSI 3.7%

PRS 2.7%
group 3 innate lymphoid cell CL0001071

CSI 1.6

rCSI 1.2%

PRS 4.8%
endocrine cell CL0000163

CSI 1.6

rCSI 8.3%

PRS 21.8%
parietal epithelial cell CL1000452

CSI 1.6

rCSI 4.3%

PRS 4.7%
pro-T cell CL0000827

CSI 1.6

rCSI 38.0%

PRS 30.7%
megakaryocyte CL0000556

CSI 1.7

rCSI 7.1%

PRS 8.7%
B-2 B cell CL0000822

CSI 1.7

rCSI 35.0%

PRS 29.4%
periportal region hepatocyte CL0019026

CSI 1.7

rCSI 6.6%

PRS 7.7%
transit amplifying cell of small intestine CL0009012

CSI 1.8

rCSI 7.8%

PRS 9.0%
natural T-regulatory cell CL0000903

CSI 1.8

rCSI 3.4%

PRS 13.4%
kidney connecting tubule epithelial cell CL1000768

CSI 1.8

rCSI 4.5%

PRS 3.7%
central memory CD4-positive, alpha-beta T cell CL0000904

CSI 1.8

rCSI 1.1%

PRS 6.5%
Merkel cell CL0000242

CSI 1.8

rCSI 42.3%

PRS 34.2%
retinal ganglion cell CL0000740

CSI 1.8

rCSI 4.0%

PRS 3.3%
erythroid progenitor cell CL0000038

CSI 1.8

rCSI 10.5%

PRS 7.3%
glutamatergic neuron CL0000679

CSI 1.8

rCSI 3.8%

PRS 5.2%
IgM plasma cell CL0000986

CSI 1.8

rCSI 8.3%

PRS 25.1%
kidney collecting duct principal cell CL1001431

CSI 1.9

rCSI 9.3%

PRS 25.0%
podocyte CL0000653

CSI 1.9

rCSI 8.2%

PRS 4.7%
B-1 B cell CL0000819

CSI 1.9

rCSI 47.9%

PRS 27.3%
effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062

CSI 1.9

rCSI 9.4%

PRS 6.1%
hematopoietic multipotent progenitor cell CL0000837

CSI 2.0

rCSI 4.7%

PRS 7.3%
pluripotent stem cell CL0002248

CSI 2.0

rCSI 59.6%

PRS 11.4%
uterine smooth muscle cell CL0002601

CSI 2.1

rCSI 13.7%

PRS 35.2%
mesenchymal stem cell CL0000134

CSI 2.1

rCSI 23.1%

PRS 8.6%
lung microvascular endothelial cell CL2000016

CSI 2.2

rCSI 41.6%

PRS 17.0%
IgG plasma cell CL0000985

CSI 2.2

rCSI 2.6%

PRS 8.1%
common lymphoid progenitor CL0000051

CSI 2.2

rCSI 2.9%

PRS 8.9%
tracheobronchial smooth muscle cell CL0019019

CSI 2.2

rCSI 3.9%

PRS 6.1%
double negative T regulatory cell CL0011024

CSI 2.2

rCSI 42.0%

PRS 38.5%

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.

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.

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Interaction Source:

Pathway Categories (for ONTOLOGY source):

Baseline Cell Type:

Baseline Cell Context(s): Comma-separated if multiple.

Target Cell Type:

Target Cell Context(s): 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.

Description
Proteins

## Summary [CSTB](/details-gene/1476), or Cystatin B, is a protein-coding gene located on chromosome 21q22.3 that functions as an intracellular inhibitor of cysteine-type endopeptidases. It plays a critical role in the negative regulation of proteolysis ([GO:0045861](https://www.ebi.ac.uk/QuickGO/term/GO:0045861)). **Overall**, expression data reveals its high significance in both immune and epithelial cell lineages, with particularly high cell significance index (CSI) scores in [elicited macrophage](/details-cell/CL0000861) (CSI: 117.87) and various ciliated epithelial cells. Clinically, mutations in [CSTB](/details-gene/1476) are causally linked to progressive myoclonus epilepsy type 1 (EPM1, Unverricht-Lundborg disease), an autosomal recessive neurodegenerative disorder ([OMIM: 254800](https://omim.org/entry/254800)) [Link](https://doi.org/10.1126/science.271.5256.1731). This dual role suggests its function is essential for both innate immune modulation and central nervous system homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [CSTB](/details-gene/1476) highlights its prominence in two major cellular compartments: the myeloid lineage of the innate immune system and various epithelial barrier tissues. **Overall**, the gene shows the highest significance in phagocytic cells, including [elicited macrophage](/details-cell/CL0000861) and [CD14-low, CD16-positive monocyte](/details-cell/CL0002396). This is consistent with its involvement in the [Innate immune system](https://reactome.org/content/detail/R-HSA-168249) and pathways such as [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695), where it likely serves to control the activity of released proteases like cathepsins. A second major site of [CSTB](/details-gene/1476) expression is in epithelial cells responsible for forming mucosal barriers. It is a significant marker for [ciliated epithelial cell](/details-cell/CL0000067), [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [colon epithelial cell](/details-cell/CL0011108), and [keratinocyte](/details-cell/CL0000312). This pattern suggests a protective role in maintaining tissue integrity against endogenous or pathogen-derived proteolytic enzymes at environmental interfaces. Conversely, [CSTB](/details-gene/1476) shows notably low significance in several distinct lineages, effectively acting as an anti-marker for them. These include cells of the adaptive immune system ([CD8-positive, alpha-beta cytotoxic T cell](/details-cell/CL0000794)), various neuronal subtypes ([retinal bipolar neuron](/details-cell/CL0000748), [cerebellar granule cell](/details-cell/CL0001031)), and mesenchymal cells like [adipocyte](/details-cell/CL0000136) and [vascular associated smooth muscle cell](/details-cell/CL0000359). This specificity underscores its specialized function within the myeloid and epithelial compartments, distinguishing it from a general housekeeping gene. ## Pathways and Molecular Function The primary molecular function of [CSTB](/details-gene/1476) is [cysteine-type endopeptidase inhibitor activity](https://www.ebi.ac.uk/QuickGO/term/GO:0004869) [Link](https://doi.org/10.1016/0006-291x(85)90216-5). By binding to and inhibiting proteases, it participates in the [negative regulation of peptidase activity](https://www.ebi.ac.uk/QuickGO/term/GO:0010466). This activity is crucial in tightly controlled biological processes where excessive proteolysis can be damaging, such as the inflammatory response mediated by neutrophils and macrophages. Its role in the [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) pathway is consistent with its function in limiting the collateral damage from enzymes released by these cells during an immune response. Cellular localization data indicates [CSTB](/details-gene/1476) is predominantly found in the [Cytoplasm](https://www.ebi.ac.uk/QuickGO/term/GO:0005737) and [Nucleus](https://www.ebi.ac.uk/QuickGO/term/GO:0005634) [Link](https://doi.org/10.1006/excr.2000.5085), suggesting it regulates intracellular protease activity, potentially related to lysosomal stability and protein turnover. However, its annotation in the [Extracellular exosome](https://www.ebi.ac.uk/QuickGO/term/GO:0070062) and [Extracellular space](https://www.ebi.ac.uk/QuickGO/term/GO:0005615) suggests it may also be secreted to modulate the extracellular environment, which is relevant for its function at epithelial barriers and sites of inflammation. Additionally, its annotation for [Rna binding](https://www.ebi.ac.uk/QuickGO/term/GO:0003723) hints at potential secondary functions beyond protease inhibition that are less well characterized. ## Research Directions While mutations in [CSTB](/details-gene/1476) are definitively linked to neurodegeneration, its high expression in non-neuronal cells, particularly myeloid and epithelial types, suggests broader physiological roles that warrant further investigation. The disconnect between its low expression in most neuronal cells and the severe neurological phenotype of its deficiency presents a key area for research. ### Proposed Hypotheses 1. **Regulation of Myeloid Cell-Mediated Inflammation:** [CSTB](/details-gene/1476) functions as a crucial brake on inflammatory responses by inhibiting cathepsins and other proteases released by activated macrophages and neutrophils. Its downregulation during chronic inflammation may exacerbate tissue damage and contribute to pathology in diseases like inflammatory bowel disease or chronic obstructive pulmonary disease. 2. **Maintenance of Epithelial Barrier Integrity:** In mucosal tissues, [CSTB](/details-gene/1476) is essential for protecting epithelial cell junctions and the extracellular matrix from proteolytic degradation. A reduction in its expression could lead to increased barrier permeability, rendering the host more susceptible to infection and inflammation. 3. **Neuroprotection via Lysosomal Stabilization:** The neurological symptoms in EPM1 may arise not from a primary role in neuronal signaling, but from a failure to protect specific, vulnerable neuronal populations from lysosomal stress. Loss of [CSTB](/details-gene/1476) could lead to leakage of lysosomal proteases into the cytoplasm, triggering a cell death cascade that manifests as progressive neurodegeneration. ### Experimental Approach To test the hypothesis that [CSTB](/details-gene/1476) is a key regulator of macrophage-mediated inflammation, a targeted functional genomics study could be performed. A CRISPR-Cas9 knockout of [CSTB](/details-gene/1476) would be generated in primary human monocytes. These cells, alongside wild-type controls, would be differentiated into macrophages and subsequently challenged with lipopolysaccharide (LPS). The functional consequences would be assessed by measuring the activity of secreted cathepsins using fluorogenic substrates, quantifying the release of key inflammatory cytokines (e.g., TNF-α, IL-1β) via ELISA, and performing RNA-sequencing to profile changes in the global inflammatory transcriptome. It is expected that [CSTB](/details-gene/1476)-deficient macrophages would exhibit a hyper-inflammatory phenotype. ### Therapeutic Potential The loss-of-function nature of [CSTB](/details-gene/1476) mutations in EPM1 suggests that therapeutic strategies should focus on **restoration or activation** of its function. Gene replacement therapy is a potential avenue for treating EPM1. For inflammatory or barrier-disruptive diseases where [CSTB](/details-gene/1476) expression may be suppressed, administration of recombinant [CSTB](/details-gene/1476) protein or the development of small molecules that enhance its expression or stability could represent a viable therapeutic strategy. Conversely, inhibition of [CSTB](/details-gene/1476) is likely to be pathogenic and does not represent a promising therapeutic approach.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

Cystatin-B

Genular Protein ID: 400739665

Symbol: CYTB_HUMAN

Name: Cystatin-B

UniProtKB Accession Codes:

P04080

Database IDs:

Citations:

PubMed ID: 3902020

Title: Amino acid sequence of the intracellular cysteine proteinase inhibitor cystatin B from human liver.

PubMed ID: 3902020

DOI: 10.1016/0006-291x(85)90216-5

PubMed ID: 8596935

Title: Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1).

PubMed ID: 8596935

DOI: 10.1126/science.271.5256.1731

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

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: 11139332

Title: Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1).

PubMed ID: 11139332

DOI: 10.1006/excr.2000.5085

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: 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: 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: 25944712

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

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 2347312

Title: The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction.

PubMed ID: 2347312

DOI: 10.1002/j.1460-2075.1990.tb08321.x

PubMed ID: 9012407

Title: Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).

PubMed ID: 9012407

Sequence Information:

Length: 98
Mass: 11140
Checksum: B8076220E19D0483
Sequence:

MMCGAPSATQ PATAETQHIA DQVRSQLEEK ENKKFPVFKA VSFKSQVVAG TNYFIKVHVG 
DEDFVHLRVF QSLPHENKPL TLSNYQTNKA KHDELTYF

Details for: CSTB

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Amino acid sequence of the intracellular cysteine proteinase inhibitor cystatin B from human liver. PubMed ID: 3902020

Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1). PubMed ID: 8596935

The DNA sequence of human chromosome 21. PubMed ID: 10830953

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1). PubMed ID: 11139332

Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. PubMed ID: 19413330

Initial characterization of the human central proteome. PubMed ID: 21269460

Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. PubMed ID: 22223895

An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. PubMed ID: 24275569

N-terminome analysis of the human mitochondrial proteome. PubMed ID: 25944712

The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction. PubMed ID: 2347312

Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1). PubMed ID: 9012407