Pathway Human Homo sapiens

RHO GTPase cycle

R-HSA-9012999 in Reactome release 97: under Signaling by Rho GTPases, with 451 genes placed in it by the mapping files and 19 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-9012999 (mouse), R-RNO-9012999 (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-9012999.4
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2007-05-15
Last updated: 2021-09-15
Events inside: 19, counted from the record

RHO family of GTPases is large and diverse, with many of its members considered to be master regulators of actin cytoskeleton. RHO GTPases are involved in the regulation of many cellular processes that depend on dynamic reorganization of the cytoskeleton, including cell migration, cell adhesion, cell division, establishment of cellular polarity and intracellular transport. As a consequence, RHO GTPases play important roles in neuronal development, immunity and cardio-vascular homeostasis. RHO GTPases are involved in the etiology of infectious diseases, congenital immunodeficiencies, neurodegenerative diseases and cancer. For review, please refer to Jaffe and Hall 2005, Lemichez and Aktories 2013, Ridley 2015, Hodge and Ridley 2016, Haga and Ridley 2016, Olson 2018, and Kalpachidou et al. 2019.

Phylogenetically, RHO GTPases can be grouped into four clusters. The first cluster consists of three subfamilies: Rho, RhoD/RhoF and Rnd. The second cluster consists of three subfamilies: Rac, Cdc42 and RhoU/RhoV. The third cluster consists of the RhoH subfamily. The fourth cluster consists of the RhoBTB subfamily. Miro GTPases and RHOBTB3 ATPase are sometimes described as Rho family members, but they are phylogenetically distant from the Rho family and constitute two separate families of Ras-like GTPases, which, besides Rho, Miro and RHOBTB3 also includes Ran, Arf, Rab and Ras families (Boureux et al. 2007). Based on their activation type, RHO GTPases can be divided into classical (typical) and atypical (reviewed by Haga and Ridley 2016, and Kalpachidou et al. 2019). Classical RHO GTPases cycle between active GTP-bound states and inactive GDP-bound states through steps that are tightly controlled by members of three classes of proteins: (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the cytoplasm, (2) guanine nucleotide exchange factors or GEFs, which destabilize the interaction between Rho proteins and their bound nucleotide, the net result of which is the exchange of bound GDP for the more abundant GTP, and (3) GTPase activating proteins or GAPs, which stimulate the low intrinsic GTP hydrolysis activity of Rho family members, thus promoting their inactivation. GDIs, GEFs, and GAPs are themselves subject to tight regulation, and the overall level of Rho activity reflects the balance of their activities. Many of the Rho-specific GEFs, GAPs, and GDIs act on multiple Rho GTPases, so that regulation of these control proteins can have complex effects on the functions of multiple Rho GTPases (reviewed by Van Aelst and D'Souza-Schorey 1997, and Hodge and Ridley 2016). The classical Rho GTPase cycle is diagrammed in the figure below. External or internal cues promote the release of Rho GTPases from the GDI inhibitory complexes, which allows them to associate with the plasma membrane, where they are activated by GEFs (1), and can signal to effector proteins (4). Then, GAPs inactivate the GTPases by accelerating the intrinsic GTPase activity, leading to the GDP bound form (2). Once again, the GDI molecules stabilize the inactive GDP bound form in the cytoplasm, waiting for further instructions (3) (Tcherkezian and Lamarche-Vane, 2007). Classical RHO GTPases include four subfamilies: Rho (includes RHOA, RHOB and RHOC), Rac (includes RAC1, RAC2, RAC3 and RHOG), Cdc42 (includes CDC42, RHOJ and RHOQ) and RhoD/RhoF (includes RHOD and RHOF) (reviewed in Haga and Ridley 2016). RHOA, the founding member of the RHO GTPase family, regulates the actin cytoskeleton, formation of stress fibers and cell contractility, which is implicated in cell adhesion and migration (Lessey et al. 2012). RHOB and RHOC functions resemble RHOA (Vega and Ridley 2018; Guan et al. 2018). RHOB is also involved in membrane trafficking and DNA repair (Vega and Ridley 2018). RAC1 regulates the cytoskeleton and the production of reactive oxygen species (ROS) (Acevedo and Gonzalez-Billault 2018), and is involved in cell adhesion and cell migration (Marei and Malliri 2017). RAC2 expression is restricted to hematopoietic cells and RAC2 is a component of the phagocytic oxidase complex in neutrophils (Troeger and Williams 2013). RAC3 shares 92% sequence identity with RAC1 and is highly expressed in neurons (de Curtis 2019). CDC42 regulate the cytoskeleton and cell polarity, and is involved in cell adhesion and migration as well as in intracellular membrane trafficking (Egorov and Polishchuk 2017; Xiao et al. 2018; Pichaud et al. 2019; Woods and Lew 2019). RHOJ is highly expressed in endothelial cells, regulating their motility and vascular morphogenesis (Leszczynska et al. 2011; Shi et al. 2016). RHOQ (also known as TC10) is highly activated on exocytosing vesicles and recycling endosomes (Donnelly et al. 2014) and is involved in trafficking of CFTR (cystic fibrosis transmembrane conductance regulator) (Cheng et al. 2005). RHOD regulates cytoskeletal dynamics and intracellular transport of vesicles (Randazzo 2003; Gad and Aspenstrom 2010; Aspenstrom et al. 2014, Aspenstrom et al. 2020). RHOF regulates cytoskeletal dynamics (Gad and Aspenstrom 2010; Aspenstrom et al. 2014, Aspenstrom et al. 2020) and promotes the formation of filopodia and stress fibers (Fan and Mellor 2012). RHOD and RHOF do possess GTPase activity and are therefore grouped with classical RHO GTPases, but they are atypical in the sense that they possess high intrinsic guanine nucleotide exchange activity and do not require GEFs for activation (Aspenstrom et al. 2020).

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 451 genes in this human pathway; showing 201 to 300, in pages of 100, sorted by symbol for reading. The order carries no ranking.

Genes Reactome places in this human pathway, page 3 of 5
Gene	Authority id	Mapping file id	Evidence codes
GeneGIT1	AuthorityHGNC:4272	Mapping file id28964 NCBI file	EvidenceTAS
GeneGIT2	AuthorityHGNC:4273	Mapping file id9815 NCBI file	EvidenceTAS
GeneGJA1	AuthorityHGNC:4274	Mapping file id2697 NCBI file	EvidenceTAS
GeneGMIP	AuthorityHGNC:24852	Mapping file id51291 NCBI file	EvidenceTAS
GeneGNA13	AuthorityHGNC:4381	Mapping file id10672 NCBI file	EvidenceTAS
GeneGOLGA3	AuthorityHGNC:4426	Mapping file id2802 NCBI file	EvidenceTAS
GeneGOLGA8R	AuthorityHGNC:44407	Mapping file id101059918 NCBI file	EvidenceTAS
GeneGOPC	AuthorityHGNC:17643	Mapping file id57120 NCBI file	EvidenceTAS
GeneGPS1	AuthorityHGNC:4549	Mapping file id2873 NCBI file	EvidenceTAS
GeneGRB2	AuthorityHGNC:4566	Mapping file id2885 NCBI file	EvidenceTAS
GeneGRB7	AuthorityHGNC:4567	Mapping file id2886 NCBI file	EvidenceTAS
GeneHGS	AuthorityHGNC:4897	Mapping file id9146 NCBI file	EvidenceTAS
GeneHINT2	AuthorityHGNC:18344	Mapping file id84681 NCBI file	EvidenceTAS
GeneHMOX2	AuthorityHGNC:5014	Mapping file id3163 NCBI file	EvidenceTAS
GeneHNRNPC	AuthorityHGNC:5035	Mapping file id3183 NCBI file	EvidenceTAS
GeneHSP90AA1	AuthorityHGNC:5253	Mapping file id3320 NCBI file	EvidenceTAS
GeneHSP90AB1	AuthorityHGNC:5258	Mapping file id3326 NCBI file	EvidenceTAS
GeneHSPE1	AuthorityHGNC:5269	Mapping file id3336 NCBI file	EvidenceTAS
GeneIL32	AuthorityHGNC:16830	Mapping file id9235 NCBI file	EvidenceTAS
GeneIQGAP1	AuthorityHGNC:6110	Mapping file id8826 NCBI file	EvidenceTAS
GeneIQGAP2	AuthorityHGNC:6111	Mapping file id10788 NCBI file	EvidenceTAS
GeneIQGAP3	AuthorityHGNC:20669	Mapping file id128239 NCBI file	EvidenceTAS
GeneITGB1	AuthorityHGNC:6153	Mapping file id3688 NCBI file	EvidenceTAS
GeneITSN1	AuthorityHGNC:6183	Mapping file id6453 NCBI file	EvidenceTAS
GeneITSN2	AuthorityHGNC:6184	Mapping file id50618 NCBI file	EvidenceTAS
GeneJAG1	AuthorityHGNC:6188	Mapping file id182 NCBI file	EvidenceTAS
GeneJUP	AuthorityHGNC:6207	Mapping file id3728 NCBI file	EvidenceTAS
GeneKALRN	AuthorityHGNC:4814	Mapping file id8997 NCBI file	EvidenceTAS
GeneKCTD13	AuthorityHGNC:22234	Mapping file id253980 NCBI file	EvidenceTAS
GeneKCTD3	AuthorityHGNC:21305	Mapping file id51133 NCBI file	EvidenceTAS
GeneKIDINS220	AuthorityHGNC:29508	Mapping file id57498 NCBI file	EvidenceTAS
GeneKIF14	AuthorityHGNC:19181	Mapping file id9928 NCBI file	EvidenceTAS
GeneKTN1	AuthorityHGNC:6467	Mapping file id3895 NCBI file	EvidenceTAS
GeneLAMTOR1	AuthorityHGNC:26068	Mapping file id55004 NCBI file	EvidenceTAS
GeneLBR	AuthorityHGNC:6518	Mapping file id3930 NCBI file	EvidenceTAS
GeneLCK	AuthorityHGNC:6524	Mapping file id3932 NCBI file	EvidenceTAS
GeneLEMD3	AuthorityHGNC:28887	Mapping file id23592 NCBI file	EvidenceTAS
GeneLETM1	AuthorityHGNC:6556	Mapping file id3954 NCBI file	EvidenceTAS
GeneLMAN1	AuthorityHGNC:6631	Mapping file id3998 NCBI file	EvidenceTAS
GeneLMNB1	AuthorityHGNC:6637	Mapping file id4001 NCBI file	EvidenceTAS
GeneLRRC1	AuthorityHGNC:14307	Mapping file id55227 NCBI file	EvidenceTAS
GeneMACO1	AuthorityHGNC:25572	Mapping file id55219 NCBI file	EvidenceTAS
GeneMAP3K11	AuthorityHGNC:6850	Mapping file id4296 NCBI file	EvidenceTAS
GeneMCAM	AuthorityHGNC:6934	Mapping file id4162 NCBI file	EvidenceTAS
GeneMCF2	AuthorityHGNC:6940	Mapping file id4168 NCBI file	EvidenceTAS
GeneMCF2L	AuthorityHGNC:14576	Mapping file id23263 NCBI file	EvidenceTAS
GeneMOSPD2	AuthorityHGNC:28381	Mapping file id158747 NCBI file	EvidenceTAS
GeneMPP7	AuthorityHGNC:26542	Mapping file id143098 NCBI file	EvidenceTAS
GeneMSI2	AuthorityHGNC:18585	Mapping file id124540 NCBI file	EvidenceTAS
GeneMTMR1	AuthorityHGNC:7449	Mapping file id8776 NCBI file	EvidenceTAS
GeneMTR	AuthorityHGNC:7468	Mapping file id4548 NCBI file	EvidenceTAS
GeneMTX1	AuthorityHGNC:7504	Mapping file id4580 NCBI file	EvidenceTAS
GeneMUC13	AuthorityHGNC:7511	Mapping file id56667 NCBI file	EvidenceTAS
GeneMYO6	AuthorityHGNC:7605	Mapping file id4646 NCBI file	EvidenceTAS
GeneMYO9A	AuthorityHGNC:7608	Mapping file id4649 NCBI file	EvidenceTAS
GeneMYO9B	AuthorityHGNC:7609	Mapping file id4650 NCBI file	EvidenceTAS
GeneNCF1	AuthorityHGNC:7660	Mapping file id653361 NCBI file	EvidenceTAS
GeneNCF2	AuthorityHGNC:7661	Mapping file id4688 NCBI file	EvidenceTAS
GeneNCF4	AuthorityHGNC:7662	Mapping file id4689 NCBI file	EvidenceTAS
GeneNCK1	AuthorityHGNC:7664	Mapping file id4690 NCBI file	EvidenceTAS
GeneNCK2	AuthorityHGNC:7665	Mapping file id8440 NCBI file	EvidenceTAS
GeneNCKAP1	AuthorityHGNC:7666	Mapping file id10787 NCBI file	EvidenceTAS
GeneNCKAP1L	AuthorityHGNC:4862	Mapping file id3071 NCBI file	EvidenceTAS
GeneNDUFA5	AuthorityHGNC:7688	Mapping file id4698 NCBI file	EvidenceTAS
GeneNDUFS3	AuthorityHGNC:7710	Mapping file id4722 NCBI file	EvidenceTAS
GeneNET1	AuthorityHGNC:14592	Mapping file id10276 NCBI file	EvidenceTAS
GeneNGEF	AuthorityHGNC:7807	Mapping file id25791 NCBI file	EvidenceTAS
GeneNHS	AuthorityHGNC:7820	Mapping file id4810 NCBI file	EvidenceTAS
GeneNIPSNAP2	AuthorityHGNC:4179	Mapping file id2631 NCBI file	EvidenceTAS
GeneNISCH	AuthorityHGNC:18006	Mapping file id11188 NCBI file	EvidenceTAS
GeneNOX1	AuthorityHGNC:7889	Mapping file id27035 NCBI file	EvidenceTAS
GeneNOX3	AuthorityHGNC:7890	Mapping file id50508 NCBI file	EvidenceTAS
GeneNOXA1	AuthorityHGNC:10668	Mapping file id10811 NCBI file	EvidenceTAS
GeneNOXO1	AuthorityHGNC:19404	Mapping file id124056 NCBI file	EvidenceTAS
GeneNSFL1C	AuthorityHGNC:15912	Mapping file id55968 NCBI file	EvidenceTAS
GeneNUDC	AuthorityHGNC:8045	Mapping file id10726 NCBI file	EvidenceTAS
GeneOBSCN	AuthorityHGNC:15719	Mapping file idENSG00000154358 Ensembl file	EvidenceTAS
GeneOCRL	AuthorityHGNC:8108	Mapping file id4952 NCBI file	EvidenceTAS
GeneOPHN1	AuthorityHGNC:8148	Mapping file id4983 NCBI file	EvidenceTAS
GeneOSBPL11	AuthorityHGNC:16397	Mapping file id114885 NCBI file	EvidenceTAS
GenePAK1	AuthorityHGNC:8590	Mapping file id5058 NCBI file	EvidenceTAS
GenePAK2	AuthorityHGNC:8591	Mapping file id5062 NCBI file	EvidenceTAS
GenePAK3	AuthorityHGNC:8592	Mapping file id5063 NCBI file	EvidenceTAS
GenePAK4	AuthorityHGNC:16059	Mapping file id10298 NCBI file	EvidenceTAS
GenePAK5	AuthorityHGNC:15916	Mapping file id57144 NCBI file	EvidenceTAS
GenePAK6	AuthorityHGNC:16061	Mapping file id56924 NCBI file	EvidenceTAS
GenePARD6A	AuthorityHGNC:15943	Mapping file id50855 NCBI file	EvidenceTAS
GenePARD6B	AuthorityHGNC:16245	Mapping file id84612 NCBI file	EvidenceTAS
GenePCDH7	AuthorityHGNC:8659	Mapping file id5099 NCBI file	EvidenceTAS
GenePDE5A	AuthorityHGNC:8784	Mapping file id8654 NCBI file	EvidenceTAS
GenePEAK1	AuthorityHGNC:29431	Mapping file id79834 NCBI file	EvidenceTAS
GenePGRMC2	AuthorityHGNC:16089	Mapping file id10424 NCBI file	EvidenceTAS
GenePHIP	AuthorityHGNC:15673	Mapping file id55023 NCBI file	EvidenceTAS
GenePICALM	AuthorityHGNC:15514	Mapping file id8301 NCBI file	EvidenceTAS
GenePIK3CA	AuthorityHGNC:8975	Mapping file id5290 NCBI file	EvidenceTAS
GenePIK3R1	AuthorityHGNC:8979	Mapping file id5295 NCBI file	EvidenceTAS
GenePIK3R2	AuthorityHGNC:8980	Mapping file id5296 NCBI file	EvidenceTAS
GenePIK3R3	AuthorityHGNC:8981	Mapping file id8503 NCBI file	EvidenceTAS
GenePKN1	AuthorityHGNC:9405	Mapping file id5585 NCBI file	EvidenceTAS
GenePKN2	AuthorityHGNC:9406	Mapping file id5586 NCBI file	EvidenceTAS

Evidence codes on this page: 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

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.

RHO GTPase cycle

Reactome's own record of this pathway

Genes Reactome places in this human pathway

Parents and children in this release's hierarchy

Parents

Children

Literature Reactome attaches