PDE5A | ENSG00000138735 | NCBI 8654

Details for: PDE5A

Gene ID: 8654

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: PDE5A

Ensembl ID: ENSG00000138735

Description: phosphodiesterase 5A

Cell Significance Landscape

Display Count:

Associated with

Cgmp effects
(R-HSA-418457)
Hemostasis
(R-HSA-109582)
Muscle contraction
(R-HSA-397014)
Nitric oxide stimulates guanylate cyclase
(R-HSA-392154)
Platelet homeostasis
(R-HSA-418346)
Rhobtb1 gtpase cycle
(R-HSA-9013422)
Rhobtb gtpase cycle
(R-HSA-9706574)
Rho gtpase cycle
(R-HSA-9012999)
Signaling by rho gtpases
(R-HSA-194315)
Signaling by rho gtpases, miro gtpases and rhobtb3
(R-HSA-9716542)
Signal transduction
(R-HSA-162582)
Smooth muscle contraction
(R-HSA-445355)
3',5'-cyclic-amp phosphodiesterase activity
(GO:0004115)
3',5'-cyclic-gmp phosphodiesterase activity
(GO:0047555)
3',5'-cyclic-nucleotide phosphodiesterase activity
(GO:0004114)
Calmodulin-activated 3',5'-cyclic-gmp phosphodiesterase activity
(GO:0048101)
Calmodulin-activated dual specificity 3',5'-cyclic-gmp, 3',5'-cyclic-amp phosphodiesterase activity
(GO:0004117)
Camp-mediated signaling
(GO:0019933)
Cellular_component
(GO:0005575)
Cgmp binding
(GO:0030553)
Cgmp catabolic process
(GO:0046069)
Cytosol
(GO:0005829)
Metal ion binding
(GO:0046872)
Negative regulation of cardiac muscle contraction
(GO:0055118)
Negative regulation of t cell proliferation
(GO:0042130)
Oocyte development
(GO:0048599)
Positive regulation of cardiac muscle hypertrophy
(GO:0010613)
Positive regulation of map kinase activity
(GO:0043406)
Positive regulation of oocyte development
(GO:0060282)
Protein binding
(GO:0005515)
Regulation of nitric oxide mediated signal transduction
(GO:0010749)
Relaxation of cardiac muscle
(GO:0055119)
T cell proliferation
(GO:0042098)

Significant Cells

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

cerebral cortex endothelial cell CL1001602

CSI 27.81

rCSI 48.1%

PRS 66.19
retinal cone cell CL0000573

CSI 25.99

rCSI 41.83%

PRS 64.89
retinal ganglion cell CL0000740

CSI 11.54

rCSI 25.5%

PRS 60.74
promyelocyte CL0000836

CSI 11.31

rCSI 16.31%

PRS 82.23
GABAergic amacrine cell CL4030027

CSI 11.13

rCSI 38.11%

PRS 62.05
S cone cell CL0003050

CSI 10.35

rCSI 45.49%

PRS 70.98
L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040

CSI 10.01

rCSI 24.33%

PRS 54.73
Schwann cell CL0002573

CSI 9.84

rCSI 27.97%

PRS 71.67
colon epithelial cell CL0011108

CSI 9.24

rCSI 9.68%

PRS 72.53
radial glial cell CL0000681

CSI 8.36

rCSI 11.61%

PRS 73.9
vascular associated smooth muscle cell CL0000359

CSI 8.29

rCSI 26.9%

PRS 73.6
glycinergic amacrine cell CL4030028

CSI 8.07

rCSI 21.03%

PRS 70.66
adipocyte CL0000136

CSI 7.89

rCSI 10.13%

PRS 65.78
ciliated epithelial cell CL0000067

CSI 7.78

rCSI 6.85%

PRS 63.8
ependymal cell CL0000065

CSI 7.54

rCSI 15.3%

PRS 53.35
caudal ganglionic eminence derived cortical interneuron CL4023064

CSI 7.46

rCSI 13.17%

PRS 55.84
innate lymphoid cell CL0001065

CSI 7.36

rCSI 15.19%

PRS 73.66
myoepithelial cell CL0000185

CSI 6.98

rCSI 17.65%

PRS 81.09
enteric smooth muscle cell CL0002504

CSI 6.64

rCSI 9.48%

PRS 76.74
myofibroblast cell CL0000186

CSI 6.41

rCSI 8.87%

PRS 73.51
L2/3 intratelencephalic projecting glutamatergic neuron CL4030059

CSI 6.26

rCSI 13.59%

PRS 62.65
microcirculation associated smooth muscle cell CL0008035

CSI 6.21

rCSI 17.99%

PRS 75.4
inhibitory interneuron CL0000498

CSI 6.2

rCSI 14.3%

PRS 63.19
Mueller cell CL0000636

CSI 6.16

rCSI 14.07%

PRS 66.4
glioblast CL0000030

CSI 5.96

rCSI 9.51%

PRS 66.91
lamp5 GABAergic cortical interneuron CL4023011

CSI 5.87

rCSI 9.86%

PRS 56.64
L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041

CSI 5.8

rCSI 20.86%

PRS 54.68
astrocyte of the cerebral cortex CL0002605

CSI 5.76

rCSI 12.91%

PRS 57.34
goblet cell CL0000160

CSI 5.69

rCSI 5.37%

PRS 74.42
fibroblast of lung CL0002553

CSI 5.41

rCSI 5.04%

PRS 76.01
mesenchymal cell CL0008019

CSI 5.4

rCSI 13.72%

PRS 68.86
L6b glutamatergic cortical neuron CL4023038

CSI 5.38

rCSI 16.81%

PRS 58.39
alveolar type 1 fibroblast cell CL4028004

CSI 5.37

rCSI 5.88%

PRS 77.84
diffuse bipolar 3a cell CL4033029

CSI 5.28

rCSI 35.94%

PRS 69.11
brush cell of tracheobronchial tree CL0002075

CSI 5.28

rCSI 15.67%

PRS 84.32
vascular leptomeningeal cell CL4023051

CSI 5.16

rCSI 9.04%

PRS 68.23
type B pancreatic cell CL0000169

CSI 5.15

rCSI 11.4%

PRS 74.3
neural crest cell CL0011012

CSI 5.14

rCSI 4.06%

PRS 63.07
near-projecting glutamatergic cortical neuron CL4023012

CSI 5.08

rCSI 19.2%

PRS 57.04
differentiation-committed oligodendrocyte precursor CL4023059

CSI 4.93

rCSI 8.96%

PRS 66.14
corticothalamic-projecting glutamatergic cortical neuron CL4023013

CSI 4.89

rCSI 28.8%

PRS 57.48
neuron CL0000540

CSI 4.87

rCSI 12.98%

PRS 63.08
pulmonary alveolar type 1 cell CL0002062

CSI 4.66

rCSI 26.87%

PRS 72.47
sst GABAergic cortical interneuron CL4023017

CSI 4.55

rCSI 5.87%

PRS 57.9
neuroblast (sensu Nematoda and Protostomia) CL0000338

CSI 4.49

rCSI 5.18%

PRS 67.35
glutamatergic neuron CL0000679

CSI 4.46

rCSI 9.17%

PRS 63.08
kidney connecting tubule epithelial cell CL1000768

CSI 4.29

rCSI 10.89%

PRS 65.24
mural cell CL0008034

CSI 4.23

rCSI 14.34%

PRS 71.29
renal interstitial pericyte CL1001318

CSI 4.23

rCSI 11.65%

PRS 70.15
neural cell CL0002319

CSI 4.21

rCSI 15.91%

PRS 58.4
amacrine cell CL0000561

CSI 4.2

rCSI 12.17%

PRS 64.27
kidney loop of Henle thin descending limb epithelial cell CL1001111

CSI 4.18

rCSI 5.93%

PRS 71.68
chondrocyte CL0000138

CSI 4.18

rCSI 6.64%

PRS 67.82
megakaryocyte CL0000556

CSI 4.14

rCSI 17.97%

PRS 82.59
neuroblast (sensu Vertebrata) CL0000031

CSI 4.13

rCSI 5.3%

PRS 71.56
retina horizontal cell CL0000745

CSI 4.12

rCSI 6.27%

PRS 71.91
interneuron CL0000099

CSI 4.03

rCSI 8.1%

PRS 64.78
bronchus fibroblast of lung CL2000093

CSI 3.9

rCSI 3.17%

PRS 75.12
lung pericyte CL0009089

CSI 3.78

rCSI 9.99%

PRS 82.88
pvalb GABAergic cortical interneuron CL4023018

CSI 3.78

rCSI 4.7%

PRS 54.59
ON parasol ganglion cell CL4033052

CSI 3.66

rCSI 51.99%

PRS 65.96
OFFx cell CL4033036

CSI 3.66

rCSI 17.21%

PRS 68.52
VIP GABAergic cortical interneuron CL4023016

CSI 3.64

rCSI 4.35%

PRS 56.62
central nervous system neuron CL2000029

CSI 3.63

rCSI 26.71%

PRS 62
melanocyte of skin CL1000458

CSI 3.55

rCSI 4.84%

PRS 42.63
retinal rod cell CL0000604

CSI 3.33

rCSI 5.87%

PRS 71.17
perivascular cell CL4033054

CSI 3.29

rCSI 4.5%

PRS 80.12
diffuse bipolar 1 cell CL4033027

CSI 3.24

rCSI 24.36%

PRS 67.29
retinal bipolar neuron CL0000748

CSI 3.23

rCSI 6.04%

PRS 63.03
parietal epithelial cell CL1000452

CSI 3.11

rCSI 8.3%

PRS 66.35
peripheral nervous system neuron CL2000032

CSI 3.11

rCSI 4.23%

PRS 66.67
hepatic stellate cell CL0000632

CSI 3.08

rCSI 11.52%

PRS 67.3
adventitial cell CL0002503

CSI 3.06

rCSI 7.3%

PRS 80.38
lung neuroendocrine cell CL1000223

CSI 2.98

rCSI 4.41%

PRS 80.01
cardiac neuron CL0010022

CSI 2.89

rCSI 9.23%

PRS 72.36
Bergmann glial cell CL0000644

CSI 2.84

rCSI 3.88%

PRS 67.13
mesodermal cell CL0000222

CSI 2.83

rCSI 3.4%

PRS 73.35
ON midget ganglion cell CL4033046

CSI 2.81

rCSI 57.23%

PRS 64.83
hepatocyte CL0000182

CSI 2.81

rCSI 5.03%

PRS 74.59
OFF midget ganglion cell CL4033047

CSI 2.8

rCSI 56.96%

PRS 66.26
rod bipolar cell CL0000751

CSI 2.78

rCSI 5%

PRS 68.36
basal cell of epidermis CL0002187

CSI 2.78

rCSI 4.93%

PRS 45.43
smooth muscle cell CL0000192

CSI 2.78

rCSI 6.64%

PRS 73.48
cerebellar granule cell CL0001031

CSI 2.74

rCSI 4.02%

PRS 67.97
GABAergic neuron CL0000617

CSI 2.7

rCSI 9.03%

PRS 59.23
choroid plexus epithelial cell CL0000706

CSI 2.65

rCSI 4.34%

PRS 64.47
interstitial cell of Cajal CL0002088

CSI 2.65

rCSI 3.37%

PRS 80.76
platelet CL0000233

CSI 2.62

rCSI 10.87%

PRS 74.5
small intestine goblet cell CL1000495

CSI 2.61

rCSI 5.72%

PRS 81.46
cardiac muscle cell CL0000746

CSI 2.56

rCSI 3.67%

PRS 64.72
pancreatic D cell CL0000173

CSI 2.53

rCSI 2.49%

PRS 78.14
direct pathway medium spiny neuron CL4023026

CSI 2.35

rCSI 56.28%

PRS 55.23
indirect pathway medium spiny neuron CL4023029

CSI 2.34

rCSI 56.51%

PRS 55.79
H2 horizontal cell CL0004218

CSI 2.34

rCSI 11.62%

PRS 70.65
sncg GABAergic cortical interneuron CL4023015

CSI 2.29

rCSI 3.68%

PRS 58.37
lung secretory cell CL1000272

CSI 2.28

rCSI 5.65%

PRS 74.55
fibroblast of cardiac tissue CL0002548

CSI 2.22

rCSI 10.62%

PRS 75.07
chandelier pvalb GABAergic cortical interneuron CL4023036

CSI 2.21

rCSI 6.91%

PRS 60.87
tracheobronchial smooth muscle cell CL0019019

CSI 2.13

rCSI 3.76%

PRS 81.59
blood vessel smooth muscle cell CL0019018

CSI 2.12

rCSI 17.22%

PRS 68.84

mesenchymal lymphangioblast CL0005021

CSI 0.2

rCSI 4.7%

PRS 86.2%
medium spiny neuron CL1001474

CSI 0.3

rCSI 2.4%

PRS 62.4%
diffuse bipolar 2 cell CL4033028

CSI 0.6

rCSI 4.7%

PRS 70.3%
diffuse bipolar 3b cell CL4033030

CSI 0.8

rCSI 5.6%

PRS 70.8%
suprabasal keratinocyte CL4033013

CSI 0.9

rCSI 1.5%

PRS 42.4%
pancreatic ductal cell CL0002079

CSI 1.0

rCSI 1.9%

PRS 78.6%
flat midget bipolar cell CL4033033

CSI 1.0

rCSI 7.0%

PRS 67.3%
regular ventricular cardiac myocyte CL0002131

CSI 1.3

rCSI 8.0%

PRS 66.7%
alveolar adventitial fibroblast CL4028006

CSI 1.3

rCSI 2.0%

PRS 77.1%
regular atrial cardiac myocyte CL0002129

CSI 1.3

rCSI 4.2%

PRS 72.4%
stromal cell CL0000499

CSI 1.3

rCSI 3.8%

PRS 70.7%
renal principal cell CL0005009

CSI 1.4

rCSI 3.6%

PRS 76.9%
pancreatic A cell CL0000171

CSI 1.4

rCSI 1.5%

PRS 78.5%
H1 horizontal cell CL0004217

CSI 1.5

rCSI 5.8%

PRS 72.0%
keratocyte CL0002363

CSI 1.6

rCSI 3.8%

PRS 79.6%
glial cell CL0000125

CSI 1.6

rCSI 6.2%

PRS 65.8%
intestinal crypt stem cell of small intestine CL0009017

CSI 1.7

rCSI 4.5%

PRS 81.0%
mesothelial cell CL0000077

CSI 1.7

rCSI 6.6%

PRS 52.8%
retinal pigment epithelial cell CL0002586

CSI 1.8

rCSI 3.5%

PRS 71.4%
kidney loop of Henle thin ascending limb epithelial cell CL1001107

CSI 1.8

rCSI 4.6%

PRS 70.4%
invaginating midget bipolar cell CL4033034

CSI 1.8

rCSI 10.6%

PRS 68.1%
mesangial cell CL0000650

CSI 1.8

rCSI 7.5%

PRS 85.7%
contractile cell CL0000183

CSI 2.0

rCSI 5.8%

PRS 74.7%
cardiac endothelial cell CL0010008

CSI 2.0

rCSI 8.0%

PRS 74.6%
bronchiolar smooth muscle cell CL4033017

CSI 2.0

rCSI 30.1%

PRS 85.9%
CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203

CSI 2.0

rCSI 2.4%

PRS 57.3%
duct epithelial cell CL0000068

CSI 2.0

rCSI 3.0%

PRS 80.3%
BEST4+ enteroycte CL4030026

CSI 2.1

rCSI 2.6%

PRS 76.6%
epicardial adipocyte CL1000309

CSI 2.1

rCSI 6.8%

PRS 73.5%
blood vessel smooth muscle cell CL0019018

CSI 2.1

rCSI 17.2%

PRS 68.8%
tracheobronchial smooth muscle cell CL0019019

CSI 2.1

rCSI 3.8%

PRS 81.6%
chandelier pvalb GABAergic cortical interneuron CL4023036

CSI 2.2

rCSI 6.9%

PRS 60.9%
fibroblast of cardiac tissue CL0002548

CSI 2.2

rCSI 10.6%

PRS 75.1%
lung secretory cell CL1000272

CSI 2.3

rCSI 5.7%

PRS 74.6%
sncg GABAergic cortical interneuron CL4023015

CSI 2.3

rCSI 3.7%

PRS 58.4%
H2 horizontal cell CL0004218

CSI 2.3

rCSI 11.6%

PRS 70.7%
indirect pathway medium spiny neuron CL4023029

CSI 2.3

rCSI 56.5%

PRS 55.8%
direct pathway medium spiny neuron CL4023026

CSI 2.4

rCSI 56.3%

PRS 55.2%
pancreatic D cell CL0000173

CSI 2.5

rCSI 2.5%

PRS 78.1%
cardiac muscle cell CL0000746

CSI 2.6

rCSI 3.7%

PRS 64.7%
small intestine goblet cell CL1000495

CSI 2.6

rCSI 5.7%

PRS 81.5%
platelet CL0000233

CSI 2.6

rCSI 10.9%

PRS 74.5%
interstitial cell of Cajal CL0002088

CSI 2.7

rCSI 3.4%

PRS 80.8%
choroid plexus epithelial cell CL0000706

CSI 2.7

rCSI 4.3%

PRS 64.5%
GABAergic neuron CL0000617

CSI 2.7

rCSI 9.0%

PRS 59.2%
cerebellar granule cell CL0001031

CSI 2.7

rCSI 4.0%

PRS 68.0%
smooth muscle cell CL0000192

CSI 2.8

rCSI 6.6%

PRS 73.5%
basal cell of epidermis CL0002187

CSI 2.8

rCSI 4.9%

PRS 45.4%
rod bipolar cell CL0000751

CSI 2.8

rCSI 5.0%

PRS 68.4%
OFF midget ganglion cell CL4033047

CSI 2.8

rCSI 57.0%

PRS 66.3%
hepatocyte CL0000182

CSI 2.8

rCSI 5.0%

PRS 74.6%
ON midget ganglion cell CL4033046

CSI 2.8

rCSI 57.2%

PRS 64.8%
mesodermal cell CL0000222

CSI 2.8

rCSI 3.4%

PRS 73.4%
Bergmann glial cell CL0000644

CSI 2.8

rCSI 3.9%

PRS 67.1%
cardiac neuron CL0010022

CSI 2.9

rCSI 9.2%

PRS 72.4%
lung neuroendocrine cell CL1000223

CSI 3.0

rCSI 4.4%

PRS 80.0%
adventitial cell CL0002503

CSI 3.1

rCSI 7.3%

PRS 80.4%
hepatic stellate cell CL0000632

CSI 3.1

rCSI 11.5%

PRS 67.3%
peripheral nervous system neuron CL2000032

CSI 3.1

rCSI 4.2%

PRS 66.7%
parietal epithelial cell CL1000452

CSI 3.1

rCSI 8.3%

PRS 66.4%
retinal bipolar neuron CL0000748

CSI 3.2

rCSI 6.0%

PRS 63.0%
diffuse bipolar 1 cell CL4033027

CSI 3.2

rCSI 24.4%

PRS 67.3%
perivascular cell CL4033054

CSI 3.3

rCSI 4.5%

PRS 80.1%
retinal rod cell CL0000604

CSI 3.3

rCSI 5.9%

PRS 71.2%
melanocyte of skin CL1000458

CSI 3.6

rCSI 4.8%

PRS 42.6%
central nervous system neuron CL2000029

CSI 3.6

rCSI 26.7%

PRS 62.0%
VIP GABAergic cortical interneuron CL4023016

CSI 3.6

rCSI 4.4%

PRS 56.6%
OFFx cell CL4033036

CSI 3.7

rCSI 17.2%

PRS 68.5%
ON parasol ganglion cell CL4033052

CSI 3.7

rCSI 52.0%

PRS 66.0%
pvalb GABAergic cortical interneuron CL4023018

CSI 3.8

rCSI 4.7%

PRS 54.6%
lung pericyte CL0009089

CSI 3.8

rCSI 10.0%

PRS 82.9%
bronchus fibroblast of lung CL2000093

CSI 3.9

rCSI 3.2%

PRS 75.1%
interneuron CL0000099

CSI 4.0

rCSI 8.1%

PRS 64.8%
retina horizontal cell CL0000745

CSI 4.1

rCSI 6.3%

PRS 71.9%
neuroblast (sensu Vertebrata) CL0000031

CSI 4.1

rCSI 5.3%

PRS 71.6%
megakaryocyte CL0000556

CSI 4.1

rCSI 18.0%

PRS 82.6%
chondrocyte CL0000138

CSI 4.2

rCSI 6.6%

PRS 67.8%
kidney loop of Henle thin descending limb epithelial cell CL1001111

CSI 4.2

rCSI 5.9%

PRS 71.7%
amacrine cell CL0000561

CSI 4.2

rCSI 12.2%

PRS 64.3%
neural cell CL0002319

CSI 4.2

rCSI 15.9%

PRS 58.4%
renal interstitial pericyte CL1001318

CSI 4.2

rCSI 11.7%

PRS 70.2%
mural cell CL0008034

CSI 4.2

rCSI 14.3%

PRS 71.3%
kidney connecting tubule epithelial cell CL1000768

CSI 4.3

rCSI 10.9%

PRS 65.2%
glutamatergic neuron CL0000679

CSI 4.5

rCSI 9.2%

PRS 63.1%
neuroblast (sensu Nematoda and Protostomia) CL0000338

CSI 4.5

rCSI 5.2%

PRS 67.4%
sst GABAergic cortical interneuron CL4023017

CSI 4.6

rCSI 5.9%

PRS 57.9%
pulmonary alveolar type 1 cell CL0002062

CSI 4.7

rCSI 26.9%

PRS 72.5%
neuron CL0000540

CSI 4.9

rCSI 13.0%

PRS 63.1%
corticothalamic-projecting glutamatergic cortical neuron CL4023013

CSI 4.9

rCSI 28.8%

PRS 57.5%
differentiation-committed oligodendrocyte precursor CL4023059

CSI 4.9

rCSI 9.0%

PRS 66.1%
near-projecting glutamatergic cortical neuron CL4023012

CSI 5.1

rCSI 19.2%

PRS 57.0%
neural crest cell CL0011012

CSI 5.1

rCSI 4.1%

PRS 63.1%
type B pancreatic cell CL0000169

CSI 5.2

rCSI 11.4%

PRS 74.3%
vascular leptomeningeal cell CL4023051

CSI 5.2

rCSI 9.0%

PRS 68.2%
brush cell of tracheobronchial tree CL0002075

CSI 5.3

rCSI 15.7%

PRS 84.3%
diffuse bipolar 3a cell CL4033029

CSI 5.3

rCSI 35.9%

PRS 69.1%
alveolar type 1 fibroblast cell CL4028004

CSI 5.4

rCSI 5.9%

PRS 77.8%
L6b glutamatergic cortical neuron CL4023038

CSI 5.4

rCSI 16.8%

PRS 58.4%
mesenchymal cell CL0008019

CSI 5.4

rCSI 13.7%

PRS 68.9%
fibroblast of lung CL0002553

CSI 5.4

rCSI 5.0%

PRS 76.0%

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.

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.

Context Genes (max 20):

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 [PDE5A](/details-gene/8654) encodes phosphodiesterase 5A, a key enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), a critical second messenger in various signaling pathways. By hydrolyzing cGMP, [PDE5A](/details-gene/8654) plays a fundamental role in regulating intracellular cGMP concentrations. The gene's expression is notably significant in diverse cell types, with its highest significance observed in the [cerebral cortex endothelial cell](/details-cell/CL1001602) and various retinal cells, including the [retinal cone cell](/details-cell/CL0000573). This expression pattern highlights its crucial involvement in modulating vascular tone, smooth muscle contraction, and sensory signal transduction. Foundational studies have cloned and characterized the human cDNA and gene, establishing its biochemical properties as a cGMP-binding, cGMP-specific phosphodiesterase ([Link](https://doi.org/10.1016/s0378-1119(98)00303-5), [Link](https://doi.org/10.1006/bbrc.1998.8769)). ## Cellular Roles and Expression Landscape The expression profile of [PDE5A](/details-gene/8654) underscores its importance in regulating cGMP-mediated signaling across multiple physiological systems, particularly within vascular and neural tissues. **Overall**, the gene shows paramount significance as a marker for [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 27.81), suggesting a primary role in regulating cerebrovascular function and blood-brain barrier dynamics. Its function in the visual system is strongly supported by its high significance in several retinal cell types, including [retinal cone cell](/details-cell/CL0000573) (CSI: 25.99), [retinal ganglion cell](/details-cell/CL0000740) (CSI: 11.54), and [S cone cell](/details-cell/CL0003050) (CSI: 10.35), implicating it as a key regulator of phototransduction and neural signal processing in the eye. Furthermore, [PDE5A](/details-gene/8654) is significant in [vascular associated smooth muscle cell](/details-cell/CL0000359) (CSI: 8.29), which is consistent with its well-characterized role in mediating vasodilation through the nitric oxide/cGMP pathway. The gene's relevance extends to the nervous system beyond the retina, with notable expression in [Schwann cell](/details-cell/CL0002573) (CSI: 9.84) and various neurons, pointing to a role in myelination and neuronal signaling. Its expression in [promyelocyte](/details-cell/CL0000836) (CSI: 11.31) also suggests a potential, though less characterized, role in hematopoietic cell development or function. ## Pathways and Molecular Function The primary molecular function of [PDE5A](/details-gene/8654) is [3',5'-cyclic-gmp phosphodiesterase activity](/details-go/GO:0047555), specifically targeting cGMP for hydrolysis. This enzymatic activity is central to its involvement in the [cGMP catabolic process](/details-go/GO:0046069). Structurally, its catalytic domain has been resolved, providing insight into its mechanism of action and interaction with drug molecules ([Link](https://doi.org/10.1038/nature01914)). Biologically, [PDE5A](/details-gene/8654) is a critical component of the nitric oxide signaling cascade. It acts downstream of cGMP synthesis, which is initiated by the [Nitric oxide stimulates guanylate cyclase](/details-pathway/R-HSA-392154) pathway. By controlling cGMP levels, [PDE5A](/details-gene/8654) directly modulates processes detailed in the [cGMP effects](/details-pathway/R-HSA-418457) pathway. This regulatory function is essential for physiological events such as [Smooth muscle contraction](/details-pathway/R-HSA-445355) and [Hemostasis](/details-pathway/R-HSA-109582). Its involvement in cardiac function is highlighted by its roles in the [negative regulation of cardiac muscle contraction](/details-go/GO:0055118) and [relaxation of cardiac muscle](/details-go/GO:0055119). Beyond its canonical roles in vascular and muscle tissue, functional annotations suggest a broader impact on cellular proliferation and development. For instance, [PDE5A](/details-gene/8654) is implicated in the [negative regulation of t cell proliferation](/details-go/GO:0042130), pointing towards a potential immunomodulatory function. ## Research Directions The well-established role of [PDE5A](/details-gene/8654) as a therapeutic target for vasodilation provides a strong foundation for exploring its function in other biological contexts where its expression is significant. **Proposed Testable Hypotheses:** 1. Given its high significance in [cerebral cortex endothelial cell](/details-cell/CL1001602), [PDE5A](/details-gene/8654) activity is a key regulator of blood-brain barrier (BBB) permeability. Inhibition of [PDE5A](/details-gene/8654) could therefore modulate neuroinflammation by altering BBB integrity or leukocyte trafficking. 2. Based on its role in the [negative regulation of t cell proliferation](/details-go/GO:0042130), [PDE5A](/details-gene/8654) functions as an intrinsic checkpoint regulator within T cells. Its pharmacological inhibition may enhance anti-tumor immunity by increasing intracellular cGMP levels, thereby lowering the threshold for T cell activation and effector function. 3. The high expression of [PDE5A](/details-gene/8654) in various retinal cells suggests that its activity is critical for tuning the sensitivity and adaptation of photoreceptor and ganglion cells. Consequently, dysregulation of [PDE5A](/details-gene/8654) may contribute to the pathophysiology of degenerative retinal diseases. **Key Experimental Approach:** To test the hypothesis that [PDE5A](/details-gene/8654) regulates BBB integrity, an *in vitro* BBB model could be constructed using human brain microvascular endothelial cells (hBMECs) cultured on transwell inserts. The expression of [PDE5A](/details-gene/8654) in these cells would first be confirmed. Next, cells would be treated with a specific [PDE5A](/details-gene/8654) inhibitor (e.g., sildenafil) or have the gene knocked down using siRNA. Barrier function would be quantitatively assessed by measuring transendothelial electrical resistance (TEER) and the paracellular flux of fluorescently-labeled dextrans of various molecular weights. A significant decrease in TEER and an increase in dextran permeability upon [PDE5A](/details-gene/8654) inhibition or knockdown would provide direct evidence for its role in maintaining BBB integrity. **Therapeutic Potential:** [PDE5A](/details-gene/8654) is already a highly successful therapeutic target, with inhibitors widely used for erectile dysfunction and pulmonary arterial hypertension. The strategy is **inhibition**, which elevates cGMP levels and promotes smooth muscle relaxation and vasodilation. The data presented here suggest that the therapeutic application of [PDE5A](/details-gene/8654) inhibitors could be expanded. Its high significance in cerebral endothelial cells makes it a compelling target for neurological disorders associated with cerebrovascular dysfunction or neuroinflammation, such as stroke or vascular dementia. Furthermore, its potential role in T cell regulation suggests that [PDE5A](/details-gene/8654) inhibitors could be repurposed as adjuvants in cancer immunotherapy to enhance the efficacy of checkpoint blockade or adoptive cell therapies.

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.

cGMP-binding cGMP-specific phosphodiesterase
G5E9C5_HUMAN

Genular Protein ID: 1396798320

Symbol: PDE5A_HUMAN

Name: cGMP-binding cGMP-specific phosphodiesterase

UniProtKB Accession Codes:

O76074 A0AV69 A8K2C4 O75026 O75887 Q86UI0 Q86V66 Q9Y6Z6

Database IDs:

Citations:

PubMed ID: 9714779

Title: Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

PubMed ID: 9714779

DOI: 10.1016/s0378-1119(98)00303-5

PubMed ID: 9716380

Title: Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene.

PubMed ID: 9716380

DOI: 10.1046/j.1432-1327.1998.2550391.x

PubMed ID: 9642111

Title: Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase.

PubMed ID: 9642111

DOI: 10.1006/bbrc.1998.8769

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 10393044

Title: Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells.

PubMed ID: 10393044

PubMed ID: 11723116

Title: Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells.

PubMed ID: 11723116

DOI: 10.1074/jbc.m106562200

PubMed ID: 25799991

Title: Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease.

PubMed ID: 25799991

DOI: 10.1038/nature14332

PubMed ID: 15260978

Title: A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases.

PubMed ID: 15260978

DOI: 10.1016/j.molcel.2004.07.005

PubMed ID: 12955149

Title: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.

PubMed ID: 12955149

DOI: 10.1038/nature01914

Sequence Information:

Length: 875
Mass: 99985
Checksum: 9E30C6C182F13388
Sequence:

MERAGPSFGQ QRQQQQPQQQ KQQQRDQDSV EAWLDDHWDF TFSYFVRKAT REMVNAWFAE 
RVHTIPVCKE GIRGHTESCS CPLQQSPRAD NSAPGTPTRK ISASEFDRPL RPIVVKDSEG 
TVSFLSDSEK KEQMPLTPPR FDHDEGDQCS RLLELVKDIS SHLDVTALCH KIFLHIHGLI 
SADRYSLFLV CEDSSNDKFL ISRLFDVAEG STLEEVSNNC IRLEWNKGIV GHVAALGEPL 
NIKDAYEDPR FNAEVDQITG YKTQSILCMP IKNHREEVVG VAQAINKKSG NGGTFTEKDE 
KDFAAYLAFC GIVLHNAQLY ETSLLENKRN QVLLDLASLI FEEQQSLEVI LKKIAATIIS 
FMQVQKCTIF IVDEDCSDSF SSVFHMECEE LEKSSDTLTR EHDANKINYM YAQYVKNTME 
PLNIPDVSKD KRFPWTTENT GNVNQQCIRS LLCTPIKNGK KNKVIGVCQL VNKMEENTGK 
VKPFNRNDEQ FLEAFVIFCG LGIQNTQMYE AVERAMAKQM VTLEVLSYHA SAAEEETREL 
QSLAAAVVPS AQTLKITDFS FSDFELSDLE TALCTIRMFT DLNLVQNFQM KHEVLCRWIL 
SVKKNYRKNV AYHNWRHAFN TAQCMFAALK AGKIQNKLTD LEILALLIAA LSHDLDHRGV 
NNSYIQRSEH PLAQLYCHSI MEHHHFDQCL MILNSPGNQI LSGLSIEEYK TTLKIIKQAI 
LATDLALYIK RRGEFFELIR KNQFNLEDPH QKELFLAMLM TACDLSAITK PWPIQQRIAE 
LVATEFFDQG DRERKELNIE PTDLMNREKK NKIPSMQVGF IDAICLQLYE ALTHVSEDCF 
PLLDGCRKNR QKWQALAEQQ EKMLINGESG QAKRN

Genular Protein ID: 1295609741

Symbol: G5E9C5_HUMAN

Name: N/A

UniProtKB Accession Codes:

G5E9C5

Database IDs:

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

Sequence Information:

Length: 823
Mass: 93630
Checksum: 4FFF1C345A9CED09
Sequence:

MVNAWFAERV HTIPVCKEGI RGHTESCSCP LQQSPRADNS APGTPTRKIS ASEFDRPLRP 
IVVKDSEGTV SFLSDSEKKE QMPLTPPRFD HDEGDQCSRL LELVKDISSH LDVTALCHKI 
FLHIHGLISA DRYSLFLVCE DSSNDKFLIS RLFDVAEGST LEEVSNNCIR LEWNKGIVGH 
VAALGEPLNI KDAYEDPRFN AEVDQITGYK TQSILCMPIK NHREEVVGVA QAINKKSGNG 
GTFTEKDEKD FAAYLAFCGI VLHNAQLYET SLLENKRNQV LLDLASLIFE EQQSLEVILK 
KIAATIISFM QVQKCTIFIV DEDCSDSFSS VFHMECEELE KSSDTLTREH DANKINYMYA 
QYVKNTMEPL NIPDVSKDKR FPWTTENTGN VNQQCIRSLL CTPIKNGKKN KVIGVCQLVN 
KMEENTGKVK PFNRNDEQFL EAFVIFCGLG IQNTQMYEAV ERAMAKQMVT LEVLSYHASA 
AEEETRELQS LAAAVVPSAQ TLKITDFSFS DFELSDLETA LCTIRMFTDL NLVQNFQMKH 
EVLCRWILSV KKNYRKNVAY HNWRHAFNTA QCMFAALKAG KIQNKLTDLE ILALLIAALS 
HDLDHRGVNN SYIQRSEHPL AQLYCHSIME HHHFDQCLMI LNSPGNQILS GLSIEEYKTT 
LKIIKQAILA TDLALYIKRR GEFFELIRKN QFNLEDPHQK ELFLAMLMTA CDLSAITKPW 
PIQQRIAELV ATEFFDQGDR ERKELNIEPT DLMNREKKNK IPSMQVGFID AICLQLYEAL 
THVSEDCFPL LDGCRKNRQK WQALAEQQEK MLINGESGQA KRN

Details for: PDE5A

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. PubMed ID: 9714779

Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. PubMed ID: 9716380

Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase. PubMed ID: 9642111

Complete sequencing and characterization of 21,243 full-length human cDNAs. PubMed ID: 14702039

Generation and annotation of the DNA sequences of human chromosomes 2 and 4. PubMed ID: 15815621

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

Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells. PubMed ID: 10393044

Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. PubMed ID: 11723116

Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. PubMed ID: 25799991

A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. PubMed ID: 15260978

Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. PubMed ID: 12955149

Initial sequencing and analysis of the human genome. PubMed ID: 11237011

The sequence of the human genome. PubMed ID: 11181995

Finishing the euchromatic sequence of the human genome. PubMed ID: 15496913

Generation and annotation of the DNA sequences of human chromosomes 2 and 4. PubMed ID: 15815621

PubMed ID: 9714779

PubMed ID: 9716380

PubMed ID: 9642111

PubMed ID: 14702039

PubMed ID: 15815621

PubMed ID: 15489334

PubMed ID: 10393044

PubMed ID: 11723116

PubMed ID: 25799991

PubMed ID: 15260978

PubMed ID: 12955149

PubMed ID: 11237011

PubMed ID: 11181995

PubMed ID: 15496913

PubMed ID: 15815621