Gene Report

Basic Information

Approved Symbol	FGFR3
Approved Name	fibroblast growth factor receptor 3
Previous Symbol	ACH
Previous Name	"achondroplasia, thanatophoric dwarfism"
Symbol Alias	CEK2, JTK4, CD333
Location	4p16.3
Position	chr4:1808990-1810599 (+)
External Links	Entrez Gene: 2261 Ensembl: ENSG00000068078 UCSC: uc003gdu.2 HGNC ID: 3690
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin

Positive relationships between FGFR3 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
FGFR3	Bernard, 2010	patients and normal controls		The expression of this gene was altered in the locus coerule...... The expression of this gene was altered in the locus coeruleus of MDD More...
FGFR 3	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 FGFR3 and other components at different levels (count: 0)

Positive relationship network of FGFR3 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 FGFR3 and MDD (count: 0)

Negative relationships between FGFR3 and other components at different levels (count: 0)

FGFR3 related SNPs in MK4MDD (count: 0)

FGFR3 related proteins in MK4MDD (count: 0)

FGFR3 related GO terms (count: 77)

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

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005783	endoplasmic reticulum	cellular component	IDA
GO:0005515	protein binding	molecular function	IPI[14732692\|22939624]
GO:0005794	Golgi apparatus	cellular component	IDA[18061161]
GO:0002009	morphogenesis of an epithelium	biological process	IEA
GO:0005634	nucleus	cellular component	IEA
GO:0021762	substantia nigra development	biological process	IEA
GO:0009986	cell surface	cellular component	IEA
GO:0090263	positive regulation of canonical Wnt signaling pathway	biological process	IEA
GO:0090080	positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	biological process	IEA
GO:0045839	negative regulation of mitotic nuclear division	biological process	IEA
GO:0007265	Ras protein signal transduction	biological process	TAS
GO:0007259	JAK-STAT cascade	biological process	TAS[10918587]
GO:0045879	negative regulation of smoothened signaling pathway	biological process	IEA
GO:0007411	axon guidance	biological process	TAS
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity	biological process	IMP[11294897]; TAS[15748888]
GO:0005524	ATP binding	molecular function	IEA
GO:0045597	positive regulation of cell differentiation	biological process	IEA
GO:0030900	forebrain development	biological process	IEA
GO:0061144	alveolar secondary septum development	biological process	IEA
GO:0000186	activation of MAPKK activity	biological process	TAS
GO:0030133	transport vesicle	cellular component	IDA[18061161]
GO:0008284	positive regulation of cell proliferation	biological process	IGI[8663044]; IMP[8663044\|11294897]
GO:0003416	endochondral bone growth	biological process	TAS[15748888]
GO:0010518	positive regulation of phospholipase activity	biological process	IMP[17561467]
GO:0030282	bone mineralization	biological process	ISS[20582225]
GO:0043410	positive regulation of MAPK cascade	biological process	IMP[11294897]
GO:0001958	endochondral ossification	biological process	TAS[15748888]
GO:0060385	axonogenesis involved in innervation	biological process	IEA
GO:0018108	peptidyl-tyrosine phosphorylation	biological process	IDA[11294897]
GO:0007264	small GTPase mediated signal transduction	biological process	TAS
GO:0042511	positive regulation of tyrosine phosphorylation of Stat1 protein	biological process	IMP[11294897\|17561467]
GO:0048471	perinuclear region of cytoplasm	cellular component	IEA
GO:0046777	protein autophosphorylation	biological process	IDA[11294897]
GO:0072148	epithelial cell fate commitment	biological process	IEA
GO:0032553	ribonucleotide binding	molecular function	IEA
GO:0005887	integral component of plasma membrane	cellular component	IDA[8663044]
GO:0001938	positive regulation of endothelial cell proliferation	biological process	IEA
GO:0005886	plasma membrane	cellular component	IDA[18061161]; TAS
GO:0060349	bone morphogenesis	biological process	ISS[20582225]; TAS[15748888]
GO:0048640	negative regulation of developmental growth	biological process	ISS[20582225]
GO:0048011	neurotrophin TRK receptor signaling pathway	biological process	TAS
GO:0002062	chondrocyte differentiation	biological process	TAS[15748888]
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	IDA[8663044]; IGI[8663044]; TAS
GO:0048712	negative regulation of astrocyte differentiation	biological process	IEA
GO:0031398	positive regulation of protein ubiquitination	biological process	IEA
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IEA
GO:0004713	protein tyrosine kinase activity	molecular function	IDA[11294897]
GO:0035019	somatic stem cell population maintenance	biological process	IEA
GO:0043525	positive regulation of neuron apoptotic process	biological process	IEA
GO:0045087	innate immune response	biological process	TAS
GO:0001501	skeletal system development	biological process	TAS[8601314]
GO:0008286	insulin receptor signaling pathway	biological process	TAS
GO:0005925	focal adhesion	cellular component	TAS[15748888]
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0090102	cochlea development	biological process	IEA
GO:0048015	phosphatidylinositol-mediated signaling	biological process	TAS
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	IMP[11294897]
GO:0009898	cytoplasmic side of plasma membrane	cellular component	IEA
GO:0038095	Fc-epsilon receptor signaling pathway	biological process	TAS
GO:0042517	positive regulation of tyrosine phosphorylation of Stat3 protein	biological process	IMP[11294897]
GO:0007267	cell-cell signaling	biological process	IEA
GO:0005576	extracellular region	cellular component	IEA
GO:1902178	fibroblast growth factor receptor apoptotic signaling pathway	biological process	IMP[17561467]
GO:0070307	lens fiber cell development	biological process	IEA
GO:0022010	central nervous system myelination	biological process	IEA
GO:0002089	lens morphogenesis in camera-type eye	biological process	IEA
GO:0070977	bone maturation	biological process	ISS[20582225]
GO:0008285	negative regulation of cell proliferation	biological process	IEA
GO:0060113	inner ear receptor cell differentiation	biological process	IEA
GO:0048546	digestive tract morphogenesis	biological process	IEA
GO:0017134	fibroblast growth factor binding	molecular function	IDA[8663044]; IPI[12815063]
GO:0005007	fibroblast growth factor-activated receptor activity	molecular function	IMP[8663044]
GO:0048010	vascular endothelial growth factor receptor signaling pathway	biological process	TAS
GO:0048678	response to axon injury	biological process	IEA
GO:0035988	chondrocyte proliferation	biological process	TAS[15748888]
GO:0005764	lysosome	cellular component	IEA

FGFR3 related KEGG pathways (count: 5)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04810	regulation of_actin_cytoskeleton	Regulation of actin cytoskeleton

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
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...
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
hsa05219	bladder cancer	Bladder cancer	Bladder cancer arise and progress along two distinctive path...... Bladder cancer arise and progress along two distinctive pathways. The first of these is often preceded by simple and papillary hyperplasia and exhibits a tumour morphology that is low-grade, superficial and papillary. Papillary carcinoma has a tendency to recur locally, but rarely invades and metastasizes. These tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. The second tumour pathway is characterized by high-grade muscle-invasive tumours, which either originate from flat carcinoma in situ (CIS)/severe dysplasia or arise de novo. Over half of these tumours show defects in the tumour suppressors p53 and/or the retinoblastoma protein (RB) genes and pathways, and over 50% of these tumours progress to local and distant metastases. Some of the cell cycle-related molecules show evidence of epigenetic modulation through aberrant promoter hypermethylation in invasive bladder cancer. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF). More...

FGFR3 related BioCarta pathways (count: 0)

FGFR3 related Reactome pathways (count: 7)

ID	Name	Description
Gene mapped Reactome pathways
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...
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_21374	shcmediated cascade	Studies have shown that Shc is phosphorylated in response to...... Studies have shown that Shc is phosphorylated in response to FGF stimulation of cells expressing FGFR. Coprecipitation of Shc had been demonstrated for p66 Shc and FGFR3 and for FGFR1 in mammalian cells expressing the virally encoded form of Src. However it had been suggested that the interaction is indirect, mediated by Src , consistent with earlier observations of FGFR complexes including Src and Shc. 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...

FGFR3 related interactors from protein-protein interaction data in HPRD (count: 39)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
FGFR3	RADIL	No	yeast 2-hybrid	16169070
FGFR3	FGF5	No	in vitro	8663044
FGFR3	SLC25A6	No	yeast 2-hybrid	16169070
FGFR3	ARAP1	No	yeast 2-hybrid	16169070
FGFR3	NDUFS6	No	yeast 2-hybrid	16169070
FGFR3	GPSM3	No	yeast 2-hybrid	14667819
FGFR3	FGF1	Yes	in vitro	10574949 , 14732692
FGFR3	EPHA4	No	in vivo;yeast 2-hybrid	16365308
FGFR3	SMG7	No	yeast 2-hybrid	16169070
FGFR3	PTK2B	Yes	in vitro;in vivo	15105428
FGFR3	FGF17	No	in vitro	10751172
FGFR3	FGF8	No	in vivo	10574949
FGFR3	FGFR3	Yes	in vitro	11294897
FGFR3	C13orf34	No	yeast 2-hybrid	16169070
FGFR3	ATF3	Yes	yeast 2-hybrid	16169070
FGFR3	RNF130	No	yeast 2-hybrid	16169070
FGFR3	FGF3	Yes	in vitro	8663044
FGFR3	FGF23	No	in vitro	12032146
FGFR3	CTSK	No	yeast 2-hybrid	16169070
FGFR3	STAT1	No	in vitro;in vivo	7657660 , 11294897 , 10918587 , 15322115 , 7543024 , 11839738 , 12817007 , 7690989 , 12637327
FGFR3	FGF7	No	in vitro	8663044
FGFR3	CCDC17	No	yeast 2-hybrid	16169070
FGFR3	CHGB	Yes	yeast 2-hybrid	16169070
FGFR3	RPL8	No	yeast 2-hybrid	16169070
FGFR3	GTF3C1	No	yeast 2-hybrid	16169070
FGFR3	FGF9	Yes	in vitro;in vivo	10574949 , 8576175
FGFR3	C6orf47	No	yeast 2-hybrid	14667819
FGFR3	KIAA1377	No	yeast 2-hybrid	16169070
FGFR3	HNRNPL	No	yeast 2-hybrid	16169070
FGFR3	FGF18	No	in vitro	10751172
FGFR3	POLA2	No	yeast 2-hybrid	16169070
FGFR3	FGF2	Yes	in vivo	10574949
FGFR3	SH2B1	No	in vivo;yeast 2-hybrid	11827956
FGFR3	FGF4	No	in vitro	8663044
FGFR3	KRT8	No	yeast 2-hybrid	16169070
FGFR3	FGF6	No	in vitro	8663044
FGFR3	HBZ	No	yeast 2-hybrid	16169070
FGFR3	STAT3	Yes	in vitro;in vivo	11940572 , 11294897 , 10918587 , 12244095 , 11350938 , 12626508 , 8626374 , 12576423 , 14551213
FGFR3	GRB2	No	in vivo	9045692

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways