cGMP-PKG signaling pathway Gene Set

Dataset KEGG Pathways 2026
Category structural or functional annotations
Type pathway
Description Cyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated intracellular cGMP level exerts its physiological action through two forms of cGMP-dependent protein kinase (PKG), cGMP-regulated phosphodiesterases (PDE2, PDE3) and cGMP-gated cation channels, among which PKGs might be the primary mediator. PKG1 isoform-specific activation of established substrates leads to reduction of cytosolic calcium concentration and/or decrease in the sensitivity of myofilaments to Ca2+ (Ca2+-desensitization), resulting in smooth muscle relaxation. In cardiac myocyte, PKG directly phosphorylates a member of the transient potential receptor canonical channel family, TRPC6, suppressing this nonselective ion channel's Ca2+ conductance, G-alpha-q agonist-induced NFAT activation, and myocyte hypertrophic responses. PKG also opens mitochondrial ATP-sensitive K+ (mitoKATP) channels and subsequent release of ROS triggers cardioprotection. (Kyoto Encyclopedia of Genes and Genomes, hsa04022)
External Link https://www.kegg.jp/entry/hsa04022
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161 proteins participating in the cGMP-PKG signaling pathway pathway from the KEGG Pathways 2026 dataset.

Symbol Name
ADCY1 adenylate cyclase 1 (brain)
ADCY2 adenylate cyclase 2 (brain)
ADCY4 adenylate cyclase 4
ADCY5 adenylate cyclase 5
ADCY6 adenylate cyclase 6
ADCY7 adenylate cyclase 7
ADCY8 adenylate cyclase 8 (brain)
ADCY9 adenylate cyclase 9
ADORA1 adenosine A1 receptor
ADORA3 adenosine A3 receptor
ADRA1A adrenoceptor alpha 1A
ADRA1B adrenoceptor alpha 1B
ADRA1D adrenoceptor alpha 1D
ADRA2A adrenoceptor alpha 2A
ADRA2B adrenoceptor alpha 2B
ADRA2C adrenoceptor alpha 2C
ADRB1 adrenoceptor beta 1
ADRB2 adrenoceptor beta 2, surface
ADRB3 adrenoceptor beta 3
AGTR1 angiotensin II receptor, type 1
AKT1 v-akt murine thymoma viral oncogene homolog 1
AKT2 v-akt murine thymoma viral oncogene homolog 2
AKT3 v-akt murine thymoma viral oncogene homolog 3
ATF4 activating transcription factor 4
ATF6B activating transcription factor 6 beta
ATP1A2 ATPase, Na+/K+ transporting, alpha 2 polypeptide
ATP1A3 ATPase, Na+/K+ transporting, alpha 3 polypeptide
ATP1A4 ATPase, Na+/K+ transporting, alpha 4 polypeptide
ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide
ATP1B2 ATPase, Na+/K+ transporting, beta 2 polypeptide
ATP1B3 ATPase, Na+/K+ transporting, beta 3 polypeptide
ATP1B4 ATPase, Na+/K+ transporting, beta 4 polypeptide
ATP2A1 ATPase, Ca++ transporting, cardiac muscle, fast twitch 1
ATP2A2 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
ATP2A3 ATPase, Ca++ transporting, ubiquitous
ATP2B1 ATPase, Ca++ transporting, plasma membrane 1
ATP2B3 ATPase, Ca++ transporting, plasma membrane 3
ATP2B4 ATPase, Ca++ transporting, plasma membrane 4
BAD BCL2-associated agonist of cell death
BDKRB2 bradykinin receptor B2
BORCS8-MEF2B BORCS8-MEF2B readthrough
CACNA1C calcium channel, voltage-dependent, L type, alpha 1C subunit
CACNA1D calcium channel, voltage-dependent, L type, alpha 1D subunit
CACNA1F calcium channel, voltage-dependent, L type, alpha 1F subunit
CACNA1S calcium channel, voltage-dependent, L type, alpha 1S subunit
CALM1 calmodulin 1 (phosphorylase kinase, delta)
CALM2 calmodulin 2 (phosphorylase kinase, delta)
CALM3 calmodulin 3 (phosphorylase kinase, delta)
CALML3 calmodulin-like 3
CALML4 calmodulin-like 4
CALML5 calmodulin-like 5
CALML6 calmodulin-like 6
CNGA1 cyclic nucleotide gated channel alpha 1
CNGB1 cyclic nucleotide gated channel beta 1
CREB1 cAMP responsive element binding protein 1
CREB3L1 cAMP responsive element binding protein 3-like 1
CREB3L2 cAMP responsive element binding protein 3-like 2
CREB3L3 cAMP responsive element binding protein 3-like 3
CREB3L4 cAMP responsive element binding protein 3-like 4
CREB5 cAMP responsive element binding protein 5
EDNRA endothelin receptor type A
EDNRB endothelin receptor type B
FXYD2 FXYD domain containing ion transport regulator 2
GATA4 GATA binding protein 4
GDNF glial cell derived neurotrophic factor
GNA11 guanine nucleotide binding protein (G protein), alpha 11 (Gq class)
GNA12 guanine nucleotide binding protein (G protein) alpha 12
GNA13 guanine nucleotide binding protein (G protein), alpha 13
GNAI1 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1
GNAI2 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2
GNAI3 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3
GNAQ guanine nucleotide binding protein (G protein), q polypeptide
GTF2I general transcription factor IIi
GUCY1A1 guanylate cyclase 1 soluble subunit alpha 1
GUCY1A2 guanylate cyclase 1, soluble, alpha 2
GUCY1B1 guanylate cyclase 1 soluble subunit beta 1
INS insulin
INSR insulin receptor
IRAG1 inositol 1,4,5-triphosphate receptor associated 1
IRS1 insulin receptor substrate 1
IRS2 insulin receptor substrate 2
IRS4 insulin receptor substrate 4
ITPR1 inositol 1,4,5-trisphosphate receptor, type 1
ITPR2 inositol 1,4,5-trisphosphate receptor, type 2
ITPR3 inositol 1,4,5-trisphosphate receptor, type 3
KCNJ8 potassium channel, inwardly rectifying subfamily J, member 8
KCNMA1 potassium channel, calcium activated large conductance subfamily M alpha, member 1
KCNMB1 potassium channel subfamily M regulatory beta subunit 1
KCNMB3 potassium channel subfamily M regulatory beta subunit 3
KCNMB4 potassium channel subfamily M regulatory beta subunit 4
KCNU1 potassium channel, subfamily U, member 1
KNG1 kininogen 1
MAP2K1 mitogen-activated protein kinase kinase 1
MAP2K2 mitogen-activated protein kinase kinase 2
MAPK1 mitogen-activated protein kinase 1
MAPK3 mitogen-activated protein kinase 3
MEF2A myocyte enhancer factor 2A
MEF2B myocyte enhancer factor 2B
MEF2C myocyte enhancer factor 2C
MEF2D myocyte enhancer factor 2D
MYH6 myosin, heavy chain 6, cardiac muscle, alpha
MYH7 myosin, heavy chain 7, cardiac muscle, beta
MYL9 myosin, light chain 9, regulatory
MYLK myosin light chain kinase
MYLK2 myosin light chain kinase 2
MYLK3 myosin light chain kinase 3
MYLK4 myosin light chain kinase family, member 4
NANOS3 nanos homolog 3 (Drosophila)
NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
NFATC3 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4
NPPA natriuretic peptide A
NPPB natriuretic peptide B
NPPC natriuretic peptide C
NPR1 natriuretic peptide receptor 1
NPRL2 nitrogen permease regulator-like 2 (S. cerevisiae)
OPRD1 opioid receptor, delta 1
PDE2A phosphodiesterase 2A, cGMP-stimulated
PDE3A phosphodiesterase 3A, cGMP-inhibited
PDE3B phosphodiesterase 3B, cGMP-inhibited
PDE5A phosphodiesterase 5A, cGMP-specific
PIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma
PIK3R5 phosphoinositide-3-kinase, regulatory subunit 5
PIK3R6 phosphoinositide-3-kinase, regulatory subunit 6
PLCB1 phospholipase C, beta 1 (phosphoinositide-specific)
PLCB2 phospholipase C, beta 2
PLCB3 phospholipase C, beta 3 (phosphatidylinositol-specific)
PLCB4 phospholipase C, beta 4
PLN phospholamban
PPIF peptidylprolyl isomerase F
PPP1CA protein phosphatase 1, catalytic subunit, alpha isozyme
PPP1CB protein phosphatase 1, catalytic subunit, beta isozyme
PPP1CC protein phosphatase 1, catalytic subunit, gamma isozyme
PPP1R12A protein phosphatase 1, regulatory subunit 12A
PPP3CA protein phosphatase 3, catalytic subunit, alpha isozyme
PPP3CB protein phosphatase 3, catalytic subunit, beta isozyme
PPP3CC protein phosphatase 3, catalytic subunit, gamma isozyme
PPP3R1 protein phosphatase 3, regulatory subunit B, alpha
PPP3R2 protein phosphatase 3, regulatory subunit B, beta
PRKCE protein kinase C, epsilon
PRKG1 protein kinase, cGMP-dependent, type I
PRKG2 protein kinase, cGMP-dependent, type II
RGS2 regulator of G-protein signaling 2
RHOA ras homolog family member A
RNASE3 ribonuclease, RNase A family, 3
ROCK1 Rho-associated, coiled-coil containing protein kinase 1
ROCK2 Rho-associated, coiled-coil containing protein kinase 2
SLC25A31 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31
SLC25A4 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4
SLC25A5 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5
SLC25A6 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6
SLC8A1 solute carrier family 8 (sodium/calcium exchanger), member 1
SLC8A2 solute carrier family 8 (sodium/calcium exchanger), member 2
SLC8A3 solute carrier family 8 (sodium/calcium exchanger), member 3
SRF serum response factor (c-fos serum response element-binding transcription factor)
TRPC6 transient receptor potential cation channel, subfamily C, member 6
VASP vasodilator-stimulated phosphoprotein
VDAC1 voltage-dependent anion channel 1
VDAC2 voltage-dependent anion channel 2
VDAC3 voltage-dependent anion channel 3