Gene Report

Basic Information

Approved Symbol	FGFR2
Approved Name	fibroblast growth factor receptor 2
Previous Symbol	KGFR, BEK, CFD1, JWS
Previous Name	"bacteria-expressed kinase", "keratinocyte growth factor receptor", "craniofacial dysostosis 1", "Jackson-Weiss syndrome"
Symbol Alias	CEK3, TK14, TK25, ECT1, K-SAM, CD332
Name Alias	"Crouzon syndrome", "Pfeiffer syndrome"
Location	10q25.3-q26
Position	chr10:123357476-123357972 (-)
External Links	Entrez Gene: 2263 Ensembl: ENSG00000066468 UCSC: uc021pzy.1 HGNC ID: 3689
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin

Positive relationships between FGFR2 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
FGFR2	Aston, 2005	patients and normal controls		Genes altered in major depressive disorder Genes altered in major depressive disorder
FGFR 2	Evans, 2004	patients and normal controls		Of the 10 FGF transcripts reliably detected, 4 were signific...... Of the 10 FGF transcripts reliably detected, 4 were significantly differentially expressed in the DLPFC of MDD subjects, including 2 FGF receptors (FGFR 2 and 3) and 2 FGF ligands (FGF 1 and 9) More...

Positive relationships between FGFR2 and other components at different levels (count: 0)

Positive relationship network of FGFR2 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between FGFR2 and MDD (count: 0)

Negative relationships between FGFR2 and other components at different levels (count: 0)

FGFR2 related SNPs in MK4MDD (count: 0)

FGFR2 related proteins in MK4MDD (count: 0)

FGFR2 related GO terms (count: 141)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0000165	MAPK cascade	biological process	TAS
GO:0006915	apoptotic process	biological process	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0045787	positive regulation of cell cycle	biological process	ISS
GO:0005515	protein binding	molecular function	IPI[1309608\|10618369\|10830168\|11069186\|11390973\|12591959\|22726438\|23597563\|25241761]
GO:0051781	positive regulation of cell division	biological process	ISS
GO:0040014	regulation of multicellular organism growth	biological process	ISS
GO:0004713	protein tyrosine kinase activity	molecular function	NAS[1697263]
GO:0060529	squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	biological process	ISS
GO:0033688	regulation of osteoblast proliferation	biological process	TAS[15190072]
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0005654	nucleoplasm	cellular component	IDA
GO:0035264	multicellular organism growth	biological process	ISS
GO:0060915	mesenchymal cell differentiation involved in lung development	biological process	ISS
GO:0031069	hair follicle morphogenesis	biological process	ISS
GO:0008284	positive regulation of cell proliferation	biological process	IDA[8663044]; IGI[8663044]; IMP[15629145]
GO:0030282	bone mineralization	biological process	ISS
GO:0016023	cytoplasmic, membrane-bounded vesicle	cellular component	IEA
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis	biological process	ISS
GO:0010453	regulation of cell fate commitment	biological process	ISS
GO:0050680	negative regulation of epithelial cell proliferation	biological process	IEA
GO:0030916	otic vesicle formation	biological process	ISS
GO:0060688	regulation of morphogenesis of a branching structure	biological process	ISS
GO:0007411	axon guidance	biological process	TAS
GO:0005576	extracellular region	cellular component	IEA
GO:0045667	regulation of osteoblast differentiation	biological process	TAS[15190072]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	ISS
GO:0043410	positive regulation of MAPK cascade	biological process	IMP[15629145]
GO:0048661	positive regulation of smooth muscle cell proliferation	biological process	IEA
GO:0060365	coronal suture morphogenesis	biological process	IEA
GO:0009887	organ morphogenesis	biological process	ISS
GO:0060349	bone morphogenesis	biological process	ISS
GO:0001701	in utero embryonic development	biological process	ISS
GO:0002053	positive regulation of mesenchymal cell proliferation	biological process	ISS
GO:0045839	negative regulation of mitotic nuclear division	biological process	IEA
GO:0060601	lateral sprouting from an epithelium	biological process	ISS
GO:0060512	prostate gland morphogenesis	biological process	ISS
GO:0048705	skeletal system morphogenesis	biological process	TAS[15190072]
GO:0018108	peptidyl-tyrosine phosphorylation	biological process	IDA[15629145\|16844695]
GO:0003149	membranous septum morphogenesis	biological process	ISS
GO:0035607	fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	biological process	ISS
GO:0022612	gland morphogenesis	biological process	ISS
GO:0021769	orbitofrontal cortex development	biological process	ISS
GO:0005737	cytoplasm	cellular component	IDA[16597614\|17471512]
GO:0010518	positive regulation of phospholipase activity	biological process	IMP[16844695]
GO:0001837	epithelial to mesenchymal transition	biological process	IEA
GO:0007265	Ras protein signal transduction	biological process	TAS
GO:0005634	nucleus	cellular component	IDA[16597614\|17471512]
GO:0032808	lacrimal gland development	biological process	ISS
GO:0016331	morphogenesis of embryonic epithelium	biological process	ISS
GO:0060442	branching involved in prostate gland morphogenesis	biological process	ISS
GO:0048286	lung alveolus development	biological process	ISS
GO:0005938	cell cortex	cellular component	IDA[17471512]
GO:0048489	synaptic vesicle transport	biological process	IEA
GO:0040036	regulation of fibroblast growth factor receptor signaling pathway	biological process	ISS
GO:0060174	limb bud formation	biological process	ISS
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0005887	integral component of plasma membrane	cellular component	IDA[15629145\|16844695]
GO:0060484	lung-associated mesenchyme development	biological process	ISS
GO:0048755	branching morphogenesis of a nerve	biological process	ISS
GO:0061031	endodermal digestive tract morphogenesis	biological process	IEA
GO:0007267	cell-cell signaling	biological process	ISS
GO:0048762	mesenchymal cell differentiation	biological process	ISS
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0005886	plasma membrane	cellular component	TAS
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	ISS
GO:0005524	ATP binding	molecular function	IEA
GO:0008201	heparin binding	molecular function	IEA
GO:0048011	neurotrophin TRK receptor signaling pathway	biological process	TAS
GO:0042472	inner ear morphogenesis	biological process	ISS
GO:0001657	ureteric bud development	biological process	ISS
GO:0009880	embryonic pattern specification	biological process	ISS
GO:0007528	neuromuscular junction development	biological process	IEA
GO:0060076	excitatory synapse	cellular component	ISS
GO:0031012	extracellular matrix	cellular component	IDA[17959718]
GO:0008286	insulin receptor signaling pathway	biological process	TAS
GO:0007264	small GTPase mediated signal transduction	biological process	TAS
GO:0038095	Fc-epsilon receptor signaling pathway	biological process	TAS
GO:0060348	bone development	biological process	ISS
GO:0035265	organ growth	biological process	ISS
GO:0060916	mesenchymal cell proliferation involved in lung development	biological process	ISS
GO:0050679	positive regulation of epithelial cell proliferation	biological process	ISS
GO:0048565	digestive tract development	biological process	ISS
GO:0060523	prostate epithelial cord elongation	biological process	ISS
GO:0060615	mammary gland bud formation	biological process	ISS
GO:0060670	branching involved in labyrinthine layer morphogenesis	biological process	ISS
GO:0055010	ventricular cardiac muscle tissue morphogenesis	biological process	ISS
GO:0060449	bud elongation involved in lung branching	biological process	ISS
GO:0021860	pyramidal neuron development	biological process	ISS
GO:0060463	lung lobe morphogenesis	biological process	ISS
GO:0030901	midbrain development	biological process	ISS
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0048333	mesodermal cell differentiation	biological process	IEA
GO:0048730	epidermis morphogenesis	biological process	ISS
GO:0043231	intracellular membrane-bounded organelle	cellular component	IDA
GO:0008589	regulation of smoothened signaling pathway	biological process	ISS
GO:0048557	embryonic digestive tract morphogenesis	biological process	ISS
GO:0017134	fibroblast growth factor binding	molecular function	IDA[8663044]; IPI[8386828\|11923311\|19224135]
GO:0001525	angiogenesis	biological process	ISS
GO:0048608	reproductive structure development	biological process	ISS
GO:0005794	Golgi apparatus	cellular component	IEA
GO:0048701	embryonic cranial skeleton morphogenesis	biological process	IMP[7874170\|7987400]
GO:0009791	post-embryonic development	biological process	ISS
GO:0016021	integral component of membrane	cellular component	NAS[1697263]
GO:0030324	lung development	biological process	ISS
GO:0000186	activation of MAPKK activity	biological process	TAS
GO:0042803	protein homodimerization activity	molecular function	IPI[16844695]
GO:0070372	regulation of ERK1 and ERK2 cascade	biological process	ISS
GO:0048568	embryonic organ development	biological process	ISS
GO:0060527	prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	biological process	ISS
GO:0060445	branching involved in salivary gland morphogenesis	biological process	ISS
GO:0048015	phosphatidylinositol-mediated signaling	biological process	TAS
GO:0042476	odontogenesis	biological process	ISS
GO:0030855	epithelial cell differentiation	biological process	ISS
GO:0070307	lens fiber cell development	biological process	IEA
GO:0003148	outflow tract septum morphogenesis	biological process	ISS
GO:0048010	vascular endothelial growth factor receptor signaling pathway	biological process	TAS
GO:0016020	membrane	cellular component	NAS[8676562]
GO:0035603	fibroblast growth factor receptor signaling pathway involved in hemopoiesis	biological process	ISS
GO:0090263	positive regulation of canonical Wnt signaling pathway	biological process	ISS
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	ISS
GO:0046777	protein autophosphorylation	biological process	IDA[15629145]
GO:0007409	axonogenesis	biological process	ISS
GO:0009986	cell surface	cellular component	IDA[16597614]
GO:0030177	positive regulation of Wnt signaling pathway	biological process	ISS
GO:0045087	innate immune response	biological process	TAS
GO:0005007	fibroblast growth factor-activated receptor activity	molecular function	IDA[8663044\|15629145]; IGI[10830168]; NAS[1400433\|1697263\|8676562]
GO:0048562	embryonic organ morphogenesis	biological process	ISS
GO:0060687	regulation of branching involved in prostate gland morphogenesis	biological process	ISS
GO:0060045	positive regulation of cardiac muscle cell proliferation	biological process	ISS
GO:0045165	cell fate commitment	biological process	ISS
GO:0060501	positive regulation of epithelial cell proliferation involved in lung morphogenesis	biological process	ISS
GO:0035602	fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow	biological process	ISS
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	IDA[8663044\|15629145]; IGI[8663044]; IPI[10830168]; TAS
GO:0060667	branch elongation involved in salivary gland morphogenesis	biological process	ISS
GO:0035604	fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	biological process	ISS
GO:0021847	ventricular zone neuroblast division	biological process	ISS
GO:0051150	regulation of smooth muscle cell differentiation	biological process	ISS
GO:0060595	fibroblast growth factor receptor signaling pathway involved in mammary gland specification	biological process	ISS

FGFR2 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04810	regulation of_actin_cytoskeleton	Regulation of actin cytoskeleton
hsa05215	prostate cancer	Prostate cancer	The identification of key molecular alterations in prostate-...... The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes that catalyze conjunction of glutathione with harmful, electrophilic molecules, thereby protecting cells from carcinogenic factors. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by such carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. After therapeutic reduction in the levels of testosterone and dihydrotestosterone, the emergence of androgen-independent prostate cancer has been associated with mutations in the androgen receptor (AR) that permit receptor activation by other ligands, increased expression of androgen receptors accompanying AR amplification, and ligand-independent androgen-receptor activation. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04144	endocytosis	Endocytosis	Endocytosis is a mechanism for cells to remove ligands, nutr...... Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type. More...
hsa05200	pathways in_cancer	Pathways in cancer
hsa04010	mapk signaling_pathway	MAPK signaling pathway	The mitogen-activated protein kinase (MAPK) cascade is a hig...... The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. More...

FGFR2 related BioCarta pathways (count: 0)

FGFR2 related Reactome pathways (count: 6)

ID	Name	Description
Gene mapped Reactome pathways
REACT_21270	pi3k cascade	The ability of growth factors to protect from apoptosis is p...... The ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which in turn affects the activity or expression of pro-apoptotic factors, which contribute to protection from apoptosis. AKT activation also blocks the activity of GSK-3b which could lead to additional antiapoptotic signals. More...
REACT_9396	fgfr ligand_binding_and_activation	FGFs bind and activate alternatively spliced forms of four t...... FGFs bind and activate alternatively spliced forms of four tyrosine kinase FGF receptors in the region between the second and third immunoglobulin domain (known as D2 and D3). The first immunoglobulin domain (D1) and a stretch of acidic residues known as an acid box in the linker between D1 and D2 impart a lower affinity to FGFs compared to receptors in which such regions are removed. FGFRs also contain a short amino acid motif within the second immunoglobulin domain that shares sequence homology with functional motifs present in neural adhesion molecules such as NCAM and N-cadherin. This so called CAM homology domain (CHD) forms a contiguous sequence with the acid box region and is crucial for this mode of activation. Interactions between the neural cell adhesion molecules are important for a number of developmental events and have also been implicated in tumor progression. Although the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. The FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif. As this motif can be spliced out of all four FGFRs, this suggests a mechanism that can regulate the interaction of the receptor with different ligand classes. From a hormonal point of view, the spatial and temporal expression patterns of FGFs and FGFRs and the ability of specific ligand-receptor pairs to actively signal are important factors regulating FGF activity in a variety of biological processes. FGF signaling activity is regulated by the binding specificity of ligands and receptors and is modulated by extrinsic cofactors such as heparan sulfate proteoglycans. More...
REACT_21310	phospholipase cmediated_cascade	Phospholipase C-gamma (PLC-gamma) is a substrate of the fibr...... Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward tyrosine-autophosphorylated regions of the FGFR. PLC activation leads to phosphatidyl inositol (Pt Ins) hydrolysis, release of intracellular calcium and activation of PKC via recruitment of the SH2 domain of PLC-g to the FGFR. Activated PLC-gamma hydrolyzes Pt Ins P2 to form diacylglygerol (DAG) and Ins P3 which stimulates calcium release and activation of calcium/calmodulin dependent protein kinases. More...
REACT_762	irs related_events	IRS is one of the mediators of insulin signalling events. It...... IRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned under IRS are examples of IRS family members acting as indicated. More family members are to be confirmed and added in the future. More...
REACT_21247	frs2mediated cascade	FRS2 is an adapter protein that links FGFR receptors to down...... FRS2 is an adapter protein that links FGFR receptors to downstream MAP kinases. Depending on tissue expression, the products of two FRS2 genes, alpha and beta (the latter also known as FRS3, or SNT-2) serve as an essential core upon which a signaling complex consisting of the tyrosine phosphatase Shp2, the adaptor Grb2, and the docking protein GAB1 is formed, leading to the activation of the RAS-MAP kinase and PI-3-kinase/AKT pathways. More...
REACT_21272	downstream signaling_of_activated_fgfr	Signaling via FGFRs is mediated via direct recruitment of si...... Signaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that become tyrosine phosphorylated in response to FGF-stimulation and form a complex with additional complement of signaling proteins. The activation loop in the catalytic domain of FGFR maintains the PTK domain in an inactive or low activity state. The activation-loop of FGFR1, for instance, contains two tyrosine residues that must be autophosphorylated for maintaining the catalytic domain in an active state. In the autoinhibited configuration, a kinase invariant proline residue at the C-terminal end of the activation loop interferes with substrate binding while allowing access to ATP in the nucleotidebinding site. Iin addition to the catalytic PTK core, the cytoplasmic domain of FGFR contains several regulatory sequences. The juxtamembrane domain of FGFRs is considerably longer than that of other receptor tyrosine kinases. This region contains a highly conserved sequence that serves as a binding site for the phosphotyrosine binding (PTB) domain of FRS2. A variety of signaling proteins are phosphorylated in response to FGF stimulation, including Shc, phospholipase-C gamma and FRS2 leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. More...

FGFR2 related interactors from protein-protein interaction data in HPRD (count: 18)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
FGFR2	FGF18	No	in vitro	10751172
FGFR2	FGF7	No	in vivo	7687739
FGFR2	FGF5	No	in vivo	11876253
FGFR2	FGF8	No	in vitro	8663044 , 10751172
FGFR2	FGF17	No	in vitro	10751172
FGFR2	CACNA1D	No	in vivo	11292657
FGFR2	FGF10	No	in vitro;in vivo	9582367
FGFR2	FGF23	No	in vitro	12032146
FGFR2	FGF9	Yes	in vivo	8576175
FGFR2	FGF1	Yes	in vitro;in vivo	10618369 , 11069186 , 14732692
FGFR2	FGF4	No	in vitro	8663044
FGFR2	FGF6	No	in vitro	8663044
FGFR2	FGF3	Yes	in vitro	8663044
FGFR2	EPHA4	No	in vivo;yeast 2-hybrid	16365308
FGFR2	PLCG1	No	in vivo	7999363
FGFR2	PTK2B	Yes	in vitro;in vivo	15105428
FGFR2	PAK4	No	in vitro;in vivo;yeast 2-hybrid	12529371
FGFR2	ITGA5	No	in vitro	15728256

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways