Pathway Human Homo sapiens

cGMP effects

R-HSA-418457 in Reactome release 97: under Nitric oxide stimulates guanylate cyclase, with 16 genes placed in it by the mapping files and 0 child pathways in the hierarchy.

The same number in the other species

Reactome writes the mouse and rat events it infers from a human pathway under the human number with the species token. A door opens only where that species' own list in this release holds the id: R-MMU-418457 (mouse), R-RNO-418457 (rat). Whether the event was inferred from this one is what the record says.

The record
The genes
Parents and children

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This page reads the pathway's record from its source while you read the rest; with scripts off the card stays at its loading line. Reload with scripts on to see it, or open the source's own page from the link in the card.

01The record

Reactome's own record of this pathway

What this tells you

The pathway list, the hierarchy and the genes on this page are read from the files Reactome publishes for Reactome release 97, built into this site on 2026-09-09: the pathway list, the hierarchy relationship file and the two gene mapping files. The record card is the one live read, Reactome's own record of this pathway.

Reactome's download page describes the mapping files: Mapping files link the source database identifier to the lowest level pathway diagram or subset of the pathway, all levels of the pathway hierarchy or database identifier to all reactions. [R13] The gene list here is the all-levels mapping of NCBI Gene ids, filled from the all-levels mapping of Ensembl ids where the NCBI file has no row for a gene; each row names which file it came from by the shape of its source id. Each row carries the evidence codes the file writes for it, as written and unranked, and both where the file writes both; no page of Reactome's documentation the survey read defines the codes, so this page does not expand them. A gene id the identity files do not name is kept as the source's own id with no door rather than turned into a symbol.

On citing what a search finds, Reactome says: It should be remembered that while we strive to contain the most current and accurate data, Reactome should not be used in citations where other primary sources of information are available. [R12] The record card prints the literature Reactome attaches to a curated pathway for that reason. The data are public domain: All data in the Reactome database and files derived from that data are licensed under the Creative Commons Public Domain Dedication (CC0). User may copy, modify, and distribute these data, even for commercial purposes, without asking for permission. Attribution is encouraged but not required. [R10] The pathway illustrations are licensed apart, under CC BY 4.0, and none is shown here.

A gene on this list is one Reactome places in this pathway in this release, and that is all the row says: it does not say the gene is expressed in a tissue or associated with a disease, which are the other two explorers' questions, read from other sources. Reactome's papers of record are [R01] [R02].

[R01] Ragueneau E, Gong C, Sinquin P, Sevilla C, Beavers D, Grentner A, et al. (2026). The Reactome Knowledgebase 2026. Nucleic Acids Research 54:D673-D681. PMID 41251150, doi 10.1093/nar/gkaf1223.
[R02] Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. (2024). The Reactome Pathway Knowledgebase 2024. Nucleic Acids Research 52:D672-D678. PMID 37941124, doi 10.1093/nar/gkad1025.
[R10] Reactome, reactome.org. License Agreement. https://reactome.org/license, read 2026-09-09.
[R12] Reactome, reactome.org. Citing us. https://reactome.org/cite, read 2026-09-09.
[R13] Reactome, reactome.org. Download. https://reactome.org/download-data, read 2026-09-09.

Stable id: R-HSA-418457.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2010-09-21
Last updated: 2016-12-21
Events inside: 4, counted from the record

Cyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by guanylate cyclases. cGMP has effects on phosphodiesterases (PDE), ion-gated channels, and the cGMP-dependent protein kinases (cGK, Protein Kinase G or PKG). It is involved in regulation of several physiological functions including vasodilation, platelet aggregation and neurotransmission. Elevation of intracellular cGMP activates PKG (Haslam et al. 1999) which regulates several intracellular molecules and pathways including the vasodilator-stimulated phosphoprotein (VASP) (Halbrugge et al. 1990) and the ERK pathway (Hood and Granger 1998, Li et al. 2001). cGMP mediates nitric oxide (NO)-induced vascular smooth muscle relaxation (Furchgott and Vanhoutte 1989). Phosphodiesterase 5 (PDE5) hydrolyzes cGMP; the PDE5 inhibitor sildenafil (Viagra) increases intracellular cGMP and thereby can be used as a treatment for erectile dysfunction (Corbin and Francis 1999). The role of the cGMP and PKG in platelet activation was controversial as increases in platelet cGMP levels were observed in response to both platelet agonists (thrombin, ADP or collagen) and inhibitors (NO donors such as sodium nitroprusside), but it is currently accepted that PKG inhibits platelet activation (Haslam et al. 1999). Consistent with this, nitric oxide (NO) donors that inhibit platelet activation enhance intracellular cGMP (Haslam et al. 1999). cGMP also plays an important stimulatory role in GPIb-IX-mediated platelet activation. Platelet responses to cGMP have been proposed to be biphasic, consisting of an early stimulatory response that promotes platelet activation followed by a delayed platelet inhibition that serves to limit the size of platelet aggregates (Li et al 2003).

Literature Reactome attaches

Physiology and pathophysiology of vascular signaling controlled by guanosine 3',5'-cyclic monophosphate-dependent protein kinase [corrected]Circulation, 2003, vol. 108, p. 2172-83PubMed 14597579
Effects of cyclic GMP on smooth muscle relaxationAdv Pharmacol, 1994, vol. 26, p. 171-94PubMed 7913615

Reactome's record lists 12 orthologous events, R-RNO-418457 (Rattus norvegicus), R-MMU-418457 (Mus musculus) among the species this site serves, and 10 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"cGMP effects". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-418457 with StableID: R-HSA-418457.3 (accessed 2026-10-01 ET). Reactome version 97 (CC0).

Reading this pathway's record from Reactome (the pathway record).Still reading. A first read of a pathway can take a while; this page waits up to 35 seconds for it, and its scripts then bring in the panel, or a line saying what did not arrive.

02The genes

Genes Reactome places in this human pathway

The mapping files place 16 genes in this human pathway; showing 1 to 16, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 1 of 1
Gene	Authority id	Mapping file id	Evidence codes
GeneIRAG1	AuthorityHGNC:7237	Mapping file id10335 NCBI file	EvidenceTAS
GeneITPR1	AuthorityHGNC:6180	Mapping file id3708 NCBI file	EvidenceTAS
GeneKCNMA1	AuthorityHGNC:6284	Mapping file id3778 NCBI file	EvidenceIEA
GeneKCNMB1	AuthorityHGNC:6285	Mapping file id3779 NCBI file	EvidenceIEA
GeneKCNMB2	AuthorityHGNC:6286	Mapping file id10242 NCBI file	EvidenceIEA
GeneKCNMB3	AuthorityHGNC:6287	Mapping file id27094 NCBI file	EvidenceIEA
GeneKCNMB4	AuthorityHGNC:6289	Mapping file id27345 NCBI file	EvidenceIEA
GenePDE10A	AuthorityHGNC:8772	Mapping file id10846 NCBI file	EvidenceTAS
GenePDE11A	AuthorityHGNC:8773	Mapping file id50940 NCBI file	EvidenceTAS
GenePDE1A	AuthorityHGNC:8774	Mapping file id5136 NCBI file	EvidenceTAS
GenePDE1B	AuthorityHGNC:8775	Mapping file id5153 NCBI file	EvidenceTAS
GenePDE2A	AuthorityHGNC:8777	Mapping file id5138 NCBI file	EvidenceTAS
GenePDE5A	AuthorityHGNC:8784	Mapping file id8654 NCBI file	EvidenceTAS
GenePDE9A	AuthorityHGNC:8795	Mapping file id5152 NCBI file	EvidenceTAS
GenePRKG1	AuthorityHGNC:9414	Mapping file id5592 NCBI file	EvidenceIEA, TAS
GenePRKG2	AuthorityHGNC:9416	Mapping file id5593 NCBI file	EvidenceIEA, TAS

Evidence codes on this page: IEA, TAS, as the mapping file writes them; a row carrying two was written twice by the file, once under each. The mapping file id says which file placed the gene: an NCBI Gene id from NCBI2Reactome_All_Levels.txt, an Ensembl gene id from Ensembl2Reactome_All_Levels.txt. The two files can disagree about a code, so a row's codes are the one file's view. Measured by this site's build over this release on 2026-09-09: of the 138,908 human pathway-gene pairs both files place, 207 (0.149 per cent, over 47 genes) carry TAS in the Ensembl file where the NCBI rows carry IEA alone.

Reactome mapping files, the human rows for this pathway · Reactome release 97 · read 2026-09-09 · Reactome downloads"NCBI2Reactome_All_Levels.txt" and "Ensembl2Reactome_All_Levels.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.

03The hierarchy

Parents and children in this release's hierarchy

Parents

Nitric oxide stimulates guanylate cyclaseR-HSA-39215422 genes

Children

None: no pathway of this release's list names this one as a parent.

Reactome's hierarchy is a graph rather than a tree: a pathway can sit under more than one parent, and the gene counts are each pathway's own placements at every level under it, so a parent's count is not the sum of its children's.

Reactome, the human pathway list and hierarchy relationship file · Reactome release 97 · read 2026-09-09 · Reactome downloads"ReactomePathways.txt" and "ReactomePathwaysRelation.txt", Reactome, release 97, https://reactome.org/download-data/ (date of access 2026-09-09). Data CC0; attribution encouraged.