Pathway Human Homo sapiens

FGFR2 alternative splicing

R-HSA-6803529 in Reactome release 97: under Signaling by FGFR2, with 27 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-6803529 (mouse), R-RNO-6803529 (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-6803529.3
Class: Pathway
Species: Homo sapiens (human)
Inferred: no: a curated human pathway
Disease pathway: no
Released: 2016-03-23
Events inside: 4, counted from the record

Alternative splicing of the FGFR2 nascent mRNA generates an epithelial specific isoform (FGFR2 IIIb) and a mesenchymal specific isoform (FGFR2 IIIc). The inclusion of exon 8 in FGFR2 IIIb or exon 9 in FGFR2 IIIc alters the C-terminal half of the D3 loop of the receptor and is responsible for the different ligand-binding specificities of the two isoforms (reviewed in Eswarakumar et al, 2005). In recent years, a number of cis- and trans-acting elements have been identified that regulate the alternative splicing event. Exon IIIb repression is mediated by the presence of weak splice sites flanking the exon, an exonic silencing sequence (ESS) within the IIIb exon and both intronic silencing sequences (ISS) upstream and downstream (Carstens et al, 2000; Del Gatto and Breathnach, 1995; Del Gatto et al, 1996; Wagner et al 2005; Wagner and Garcia-Blanco, 2001). Binding of hnRNPA1, PTB1, SR family proteins and other factors to these elements represses the IIIb exon and promotes FGFR2 IIIc expression in mesenchymal cells (Del Gatto-Konczak et al, 1999; Carstens et al, 2000; Wagner et al, 2005; Wagner and Garcia-Blanco, 2001; Wagner and Garcia-Blanco, 2002). In epithelial cells, recruitment of epithelial specific factors shifts the splicing events to favour inclusion of exon 8. ESPN1 and ESPN2 are epithelial-specific factors that bind to an ISE/ISS-3 (intronic splicing enhancer/intronic splicing silencer-3) region within intron 8 to promote FGFR2 IIIb-specific splicing (Warzecha et al, 2009). A complex of RBFOX2, hnRNPH1 and hnRNPF also contribute to epithelial-specific splicing by competing for binding to a site that is occupied by the SR proteins ASF/SF2 in mesenchymal cells (Baraniak et al, 2006; Mauger et al, 2008). Other proteins and sequences have also been identified that appear to contribute to the regulated expression of FGFR2b and FGFR2c, but the full details of the alternative splicing event remain to be worked out (Muh et al, 2002; Newman et al, 2006; Del Gatto et al, 2000; Hovhannisyan and Carstens, 2007).

Literature Reactome attaches

Cellular signaling by fibroblast growth factor receptorsCytokine Growth Factor Rev, 2005, vol. 16, p. 139-49PubMed 15863030
An intronic splicing silencer causes skipping of the IIIb exon of fibroblast growth factor receptor 2 through involvement of polypyrimidine tract binding proteinMol. Cell. Biol., 2000, vol. 20, p. 7388-400PubMed 10982855
Exon and intron sequences, respectively, repress and activate splicing of a fibroblast growth factor receptor 2 alternative exonMol. Cell. Biol., 1995, vol. 15, p. 4825-34PubMed 7651400
The exon sequence TAGG can inhibit splicingNucleic Acids Res., 1996, vol. 24, p. 2017-21PubMed 8668531
Characterization of the intronic splicing silencers flanking FGFR2 exon IIIbJ. Biol. Chem., 2005, vol. 280, p. 14017-27PubMed 15684416
Polypyrimidine tract binding protein antagonizes exon definitionMol. Cell. Biol., 2001, vol. 21, p. 3281-8PubMed 11313454
hnRNP A1 recruited to an exon in vivo can function as an exon splicing silencerMol. Cell. Biol., 1999, vol. 19, p. 251-60PubMed 9858549
RNAi-mediated PTB depletion leads to enhanced exon definitionMol. Cell, 2002, vol. 10, p. 943-9PubMed 12419237
ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicingMol. Cell, 2009, vol. 33, p. 591-601PubMed 19285943
Fox-2 mediates epithelial cell-specific fibroblast growth factor receptor 2 exon choiceMol. Cell. Biol., 2006, vol. 26, p. 1209-22PubMed 16449636
hnRNP H and hnRNP F complex with Fox2 to silence fibroblast growth factor receptor 2 exon IIIcMol. Cell. Biol., 2008, vol. 28, p. 5403-19PubMed 18573884
A Non-sequence-specific double-stranded RNA structural element regulates splicing of two mutually exclusive exons of fibroblast growth factor receptor 2 (FGFR2)J. Biol. Chem., 2002, vol. 277, p. 50143-54PubMed 12393912
Identification of RNA-binding proteins that regulate FGFR2 splicing through the use of sensitive and specific dual color fluorescence minigene assaysRNA, 2006, vol. 12, p. 1129-41PubMed 16603716
The RNA-binding protein TIA-1 is a novel mammalian splicing regulator acting through intron sequences adjacent to a 5' splice siteMol. Cell. Biol., 2000, vol. 20, p. 6287-99PubMed 10938105
Heterogeneous ribonucleoprotein m is a splicing regulatory protein that can enhance or silence splicing of alternatively spliced exonsJ. Biol. Chem., 2007, vol. 282, p. 36265-74PubMed 17959601

Reactome's record lists 8 orthologous events, R-RNO-6803529 (Rattus norvegicus), R-MMU-6803529 (Mus musculus) among the species this site serves, and 6 in species this site opens no page for.

Reactome ContentService, this pathway's record · Reactome v97 · read 2026-10-01 ET · Reactome pathway browser"FGFR2 alternative splicing". Reactome, release 97, https://reactome.org/PathwayBrowser/#/R-HSA-6803529 with StableID: R-HSA-6803529.3 (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 27 genes in this human pathway; showing 1 to 27, 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
GeneESRP1	AuthorityHGNC:25966	Mapping file id54845 NCBI file	EvidenceTAS
GeneESRP2	AuthorityHGNC:26152	Mapping file id80004 NCBI file	EvidenceTAS
GeneFGFR2	AuthorityHGNC:3689	Mapping file idENSG00000066468 Ensembl file	EvidenceTAS
GeneGTF2F1	AuthorityHGNC:4652	Mapping file id2962 NCBI file	EvidenceTAS
GeneGTF2F2	AuthorityHGNC:4653	Mapping file id2963 NCBI file	EvidenceTAS
GeneHNRNPA1	AuthorityHGNC:5031	Mapping file id3178 NCBI file	EvidenceTAS
GeneHNRNPF	AuthorityHGNC:5039	Mapping file id3185 NCBI file	EvidenceTAS
GeneHNRNPH1	AuthorityHGNC:5041	Mapping file id3187 NCBI file	EvidenceTAS
GeneHNRNPM	AuthorityHGNC:5046	Mapping file id4670 NCBI file	EvidenceTAS
GeneNCBP1	AuthorityHGNC:7658	Mapping file id4686 NCBI file	EvidenceTAS
GeneNCBP2	AuthorityHGNC:7659	Mapping file id22916 NCBI file	EvidenceTAS
GenePOLR2A	AuthorityHGNC:9187	Mapping file id5430 NCBI file	EvidenceTAS
GenePOLR2B	AuthorityHGNC:9188	Mapping file id5431 NCBI file	EvidenceTAS
GenePOLR2C	AuthorityHGNC:9189	Mapping file id5432 NCBI file	EvidenceTAS
GenePOLR2D	AuthorityHGNC:9191	Mapping file id5433 NCBI file	EvidenceTAS
GenePOLR2E	AuthorityHGNC:9192	Mapping file id5434 NCBI file	EvidenceTAS
GenePOLR2F	AuthorityHGNC:9193	Mapping file id5435 NCBI file	EvidenceTAS
GenePOLR2G	AuthorityHGNC:9194	Mapping file id5436 NCBI file	EvidenceTAS
GenePOLR2H	AuthorityHGNC:9195	Mapping file id5437 NCBI file	EvidenceTAS
GenePOLR2I	AuthorityHGNC:9196	Mapping file id5438 NCBI file	EvidenceTAS
GenePOLR2J	AuthorityHGNC:9197	Mapping file id5439 NCBI file	EvidenceTAS
GenePOLR2K	AuthorityHGNC:9198	Mapping file id5440 NCBI file	EvidenceTAS
GenePOLR2L	AuthorityHGNC:9199	Mapping file id5441 NCBI file	EvidenceTAS
GenePTBP1	AuthorityHGNC:9583	Mapping file id5725 NCBI file	EvidenceTAS
GeneRBFOX2	AuthorityHGNC:9906	Mapping file id23543 NCBI file	EvidenceTAS
GeneTIA1	AuthorityHGNC:11802	Mapping file id7072 NCBI file	EvidenceTAS
GeneTIAL1	AuthorityHGNC:11804	Mapping file id7073 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

Parents

Signaling by FGFR2R-HSA-565473873 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.