Pathway Human Homo sapiens

EPHA-mediated growth cone collapse

R-HSA-3928663 in Reactome release 97: under EPH-Ephrin signaling, with 29 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-3928663 (mouse), R-RNO-3928663 (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-3928663.5
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2014-06-10
Last updated: 2017-09-27
Events inside: 4, counted from the record

EPH/Ephrin signaling is coupled to Rho family GTPases such as Rac, Rho and Cdc42 that connect bidirectional receptor-ligand interactions to changes in the actin cytoskeleton (Noren & Pasquale 2004, Groeger & Nobes 2007). RHOA regulates actin dynamics and is involved in EPHA-induced growth cone collapse. This is mediated by ephexins. Ephexin, a guanine nucleotide exchange factor for Rho GTPases, interacts with the EPHA kinase domain and its subsequent activation differentially affects Rho GTPases, such that RHOA is activated, whereas Cdc42 and Rac1 are inhibited. Activation of RHOA, and inhibition of Cdc42 and Rac, shifts actin cytoskeleton to increased contraction and reduced expansion leading to growth-cone collapse (Shamah et al. 2001, Sahin et al. 2005). The activation of EPH receptors in growing neurons typically, but not always, leads to a growth cone collapse response and retraction from an ephrin-expressing substrate (Poliakov et al. 2004, Pasquale 2005). EPHA-mediated repulsive responses prevent axons from growing into regions of excessive ephrin-A concentration, such as the posterior end of the superior colliculus (Pasquale 2005).

Literature Reactome attaches

Eph receptor-ephrin bidirectional signals that target Ras and Rho proteinsCell. Signal., 2004, vol. 16, p. 655-66PubMed 15093606
Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retractionBiochem. J., 2007, vol. 404, p. 23-9PubMed 17300218
EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexinCell, 2001, vol. 105, p. 233-44PubMed 11336673
Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapseNeuron, 2005, vol. 46, p. 191-204PubMed 15848799
Eph receptor signalling casts a wide net on cell behaviourNat. Rev. Mol. Cell Biol., 2005, vol. 6, p. 462-75PubMed 15928710
Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assemblyDev. Cell, 2004, vol. 7, p. 465-80PubMed 15469835

Reactome's record lists 10 orthologous events, R-RNO-3928663 (Rattus norvegicus), R-MMU-3928663 (Mus musculus) among the species this site serves, and 8 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-09-30 ET · Reactome pathway browser"EPHA-mediated growth cone collapse". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-3928663 with StableID: R-HSA-3928663.5 (accessed 2026-09-30 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 29 genes in this human pathway; showing 1 to 29, 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
GeneEFNA1	AuthorityHGNC:3221	Mapping file id1942 NCBI file	EvidenceIEA, TAS
GeneEFNA2	AuthorityHGNC:3222	Mapping file id1943 NCBI file	EvidenceIEA, TAS
GeneEFNA3	AuthorityHGNC:3223	Mapping file id1944 NCBI file	EvidenceIEA, TAS
GeneEFNA4	AuthorityHGNC:3224	Mapping file id1945 NCBI file	EvidenceIEA, TAS
GeneEFNA5	AuthorityHGNC:3225	Mapping file id1946 NCBI file	EvidenceIEA, TAS
GeneEPHA1	AuthorityHGNC:3385	Mapping file id2041 NCBI file	EvidenceIEA, TAS
GeneEPHA10	AuthorityHGNC:19987	Mapping file id284656 NCBI file	EvidenceIEA, TAS
GeneEPHA2	AuthorityHGNC:3386	Mapping file id1969 NCBI file	EvidenceIEA, TAS
GeneEPHA3	AuthorityHGNC:3387	Mapping file id2042 NCBI file	EvidenceIEA, TAS
GeneEPHA4	AuthorityHGNC:3388	Mapping file id2043 NCBI file	EvidenceIEA, TAS
GeneEPHA5	AuthorityHGNC:3389	Mapping file id2044 NCBI file	EvidenceIEA, TAS
GeneEPHA6	AuthorityHGNC:19296	Mapping file id285220 NCBI file	EvidenceIEA, TAS
GeneEPHA7	AuthorityHGNC:3390	Mapping file id2045 NCBI file	EvidenceIEA, TAS
GeneEPHA8	AuthorityHGNC:3391	Mapping file id2046 NCBI file	EvidenceIEA, TAS
GeneFYN	AuthorityHGNC:4037	Mapping file id2534 NCBI file	EvidenceIEA, TAS
GeneLYN	AuthorityHGNC:6735	Mapping file id4067 NCBI file	EvidenceIEA, TAS
GeneMYH10	AuthorityHGNC:7568	Mapping file id4628 NCBI file	EvidenceIEA
GeneMYH11	AuthorityHGNC:7569	Mapping file id4629 NCBI file	EvidenceIEA
GeneMYH14	AuthorityHGNC:23212	Mapping file id79784 NCBI file	EvidenceIEA
GeneMYH9	AuthorityHGNC:7579	Mapping file id4627 NCBI file	EvidenceIEA
GeneMYL12B	AuthorityHGNC:29827	Mapping file id103910 NCBI file	EvidenceIEA
GeneMYL6	AuthorityHGNC:7587	Mapping file id4637 NCBI file	EvidenceIEA
GeneMYL9	AuthorityHGNC:15754	Mapping file id10398 NCBI file	EvidenceIEA
GeneNGEF	AuthorityHGNC:7807	Mapping file id25791 NCBI file	EvidenceIEA, TAS
GeneRHOA	AuthorityHGNC:667	Mapping file id387 NCBI file	EvidenceIEA, TAS
GeneROCK1	AuthorityHGNC:10251	Mapping file id6093 NCBI file	EvidenceIEA
GeneROCK2	AuthorityHGNC:10252	Mapping file id9475 NCBI file	EvidenceIEA
GeneSRC	AuthorityHGNC:11283	Mapping file id6714 NCBI file	EvidenceIEA, TAS
GeneYES1	AuthorityHGNC:12841	Mapping file id7525 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

EPH-Ephrin signalingR-HSA-268233492 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.