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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

FGFR4 Gene

protein-coding   GIFtS: 76
GCID: GC05P176513

fibroblast growth factor receptor 4
 Explore 57 diseases affiliated with
FGFR4 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for FGFR4    

Aliases
for FGFR4 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Fibroblast Growth Factor Receptor 41 2     Hydroxyaryl-Protein Kinase2
JTK21 2 3     Protein-Tyrosine Kinase2
CD3341 2     Tyrosine Kinase Related To Fibroblast Growth Factor Receptor2
FGFR-42 3     Tyrosylprotein Kinase2
TKF2 3     CD334 Antigen3
EC 2.7.10.13 8     EC 2.7.108

External Ids:    HGNC: 36911   Entrez Gene: 22642   Ensembl: ENSG000001608677   OMIM: 1349355   UniProtKB: P224553   

Export aliases for FGFR4 gene to outside databases

Previous GC identifers: GC05P176887 GC05P177356 GC05P176449 GC05P176494 GC05P176446 GC05P171435


Summaries
for FGFR4 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for FGFR4:
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence
is highly conserved between members and throughout evolution. FGFR family members differ from one another in their
ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular
region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a
cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors,
setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic
organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative
splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies
between three alternate forms, as indicated for members 1-3. This particular family member preferentially binds acidic
fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor
samples, suggesting a role in breast and ovarian tumorigenesis. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: FGFR4_HUMAN, P22455
Function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in
the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid
biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of
the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1
and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the
production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of
FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and
the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of
the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization
and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase
activation or impair normal FGFR4 inactivation lead to aberrant signaling

summary for FGFR4:
Fibroblast growth factors (FGFs) (FGF1 - 10 and 16 - 23) are mitogenic signaling molecules that have roles
in angiogenesis, wound healing, cell migration, neural outgrowth and embryonic development. FGFs bind
heparan sulfate glycosaminoglycans (HSGAGs), which facilitates dimerization (activation) of FGF receptors
(FGFRs). FGFRs are transmembrane catalytic receptors that have intracellular tyrosine kinase activity. There
are four human genes encoding FGFRs, which produce seven different receptors (FGFR1b, FGFR1c, FGFR2b,
FGFR2c, FGFR3b, FGFR3c and FGFR4) due to alternative splicing events occurring both in the extracellular and
intracellular regions. The alternative splice isoforms are generally tissue specific: the b isoform is
expressed in epithelial tissue, whereas the c isoform is expressed in mesenchymal tissue. HSGAG-FGF-FGFR
binding initiates FGFR dimerization, enabling the cytoplasmic kinase domains to transphosphorylate tyrosine
residues and become activated. HSGAGs also function to stabilize FGF-FGFR binding and prevent FGF
degradation. FGFRs couple to the PLCgamma, MAPK and PI3-K/Akt intracellular signaling cascades and there is
evidence of cross talk with the Notch signaling pathway. In addition, some activated FGF-FGFR complexes are
endocytosed and function directly in the cytosol and/or nucleus of the cell. Mutations in FGFR genes are the
cause of several human developmental disorders characterized by skeletal abnormalities such as
achondroplasia, and upregulation of FGFR expression may lead to cell transformation and cancer.

Gene Wiki entry for FGFR4 (Fibroblast growth factor receptor 4)


Genomic Views
for FGFR4 gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000005.9  NC_018916.1  NT_023133.13  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the FGFR4 gene promoter:
         AREB6   ER-alpha   AhR   AML1a   SEF-1 (1)   AP-4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: FGFR4 promoter sequence
   Search SABiosciences Chromatin IP Primers for FGFR4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FGFR4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 5q35.1-qter   Ensembl cytogenetic band:  5q35.2   HGNC cytogenetic band: 5q33-qter

FGFR4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FGFR4 gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05P176513:  view genomic region     (about GC identifiers)

Start:
 176,513,887 bp from pter      End:
 176,525,145 bp from pter
Size:
 11,259 bases      Orientation:
 plus strand

Proteins
for FGFR4 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
UniProtKB/Swiss-Prot: FGFR4_HUMAN, P22455 (See protein sequence)
Recommended Name: Fibroblast growth factor receptor 4 precursor  
Size: 802 amino acids; 87954 Da
Subunit: Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6, FGF8, FGF9, FGF16, FGF17,
FGF18, FGF19, FGF21 and FGF23 (in vitro). Binding affinity for FGF family members is enhanced by interactions between
FGFs and heparan sulfate proteoglycans. Interacts with KLB; this strongly increases the affinity for FGF19 and FGF23.
Affinity for FGF19 is strongly increased by KLB and sulfated glycosaminoglycans. KLB and KL both interact with the
core-glycosylated FGFR4 in the endoplasmic reticulum and promote its degradation, so that only FGFR4 with fully mature
N-glycans is expressed at the cell surface. Identified in a complex with NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43
and CTTN. Interacts with MMP14 and HIP1
Subcellular location: Cell membrane; Single-pass type I membrane protein. Endosome. Endoplasmic reticulum.
Note=Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane
Subcellular location: Isoform 2: Secreted
1 PDB 3D structure from and Proteopedia for FGFR4:
1QCT (3D)    
Secondary accessions: O43785 Q14309 Q71TW8 Q8TDA0
Alternative splicing: 2 isoforms:  P22455-1   P22455-2   

Explore the universe of human proteins at neXtProt for FGFR4: NX_P22455

Post-translational modifications:

  • N-glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF191
  • Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated1
  • Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes
    • receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the
    two FGFR molecules present in the dimer1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P22455

    • 4/30 DME Specific Peptides for FGFR4 (P22455) (see all 30)
     RDLAARN  PHIQWLK  NIINLLG  WSLVMES 

    FGFR4 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins (3 alternative transcripts): 
    NP_002002.3  NP_075252.2  NP_998812.1  

    ENSEMBL proteins: 
     ENSP00000292408   ENSP00000424905   ENSP00000377259   ENSP00000426492   ENSP00000424960  
     ENSP00000427222   ENSP00000422889   ENSP00000377254   ENSP00000395164   ENSP00000424670  
     ENSP00000292410  
    Reactome Protein details: P22455
    Human Recombinant Protein Products: 
    EMD Millipore Purified and/or Recombinant FGFR4 Protein
    R&D Systems Recombinant & Natural Proteins for FGFR4 (FGF R4)
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein: FGFR4
    OriGene Protein Over-expression Lysate (see all 5): FGFR4
    OriGene Custom Protein Services for FGFR4 
    GenScript Custom Purified and Recombinant Proteins Services for FGFR4
    Novus Biologicals FGFR4 Proteins
    Novus Biologicals FGFR4 Lysates
    Sino Biological Recombinant Protein for FGFR4
    ProSpec Recombinant Protein for FGFR4
    Uscn Proteins for FGFR4

    Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region IEA--
    GO:0005634nucleus IDA--
    GO:0005730NOT nucleolus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005768endosome IEA--


    FGFR4 for ontologies           About GeneDecksing



    FGFR4 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of FGFR4
    R&D Systems Antibodies for FGFR4 (FGF R4)
    Cell Signaling Technology (CST) Antibodies for FGFR4 
    OriGene Antibodies (see all 2): FGFR4
    OriGene Custom Antibody Services for FGFR4 
    GenScript Custom Superior Antibodies Services for FGFR4
    Novus Biologicals FGFR4 Antibodies
    Abcam antibodies for FGFR4 
    Uscn Antibodies for FGFR4
    ThermoFisher Antibodies for FGFR4

    Assay Products for FGFR4: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    R&D Systems ELISAs for FGFR4 (FGF R4)         (see all)
    GenScript FGFR4-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for FGFR4

    Protein Domains /
    Families
    for FGFR4 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    FGFR4 for domains           About GeneDecksing

    5/11 InterPro domains/families (see all 11):
     IPR003598 Ig_sub2
     IPR017441 Protein_kinase_ATP_BS
     IPR013098 Ig_I-set
     IPR011009 Kinase-like_dom
     IPR016248 Tyr_kinase_fibroblast_GF_rcpt

    Graphical View of Domain Structure for InterPro Entry P22455

    ProtoNet protein and cluster: P22455

    3 Blocks protein families:
    IPB003598 Immunoglobulin C-2 type
    IPB008266 Tyrosine protein kinase
    IPB013098 Immunoglobulin I-set


    UniProtKB/Swiss-Prot: FGFR4_HUMAN, P22455
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor
    subfamily
    Similarity: Contains 3 Ig-like C2-type (immunoglobulin-like) domains
    Similarity: Contains 1 protein kinase domain


    Function
    for FGFR4 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         UniProtKB/Swiss-Prot: FGFR4_HUMAN, P22455
    Function: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in
    the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid
    biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of
    the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1
    and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the
    production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of
    FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and
    the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of
    the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization
    and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase
    activation or impair normal FGFR4 inactivation lead to aberrant signaling
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to
    dimerization and activation by autophosphorylation on tyrosine residues

         Genatlas biochemistry entry for FGFR4:
    fibroblast growth factor receptor 4,involved in the development of endoderm derivatives and in skeletal muscle
    formation

    Enzyme Numbers (IUBMB): EC 2.7.10.11 2 EC 2.7.102

    miRNA
    Products:            		 OriGene 3'-UTR Clone (see all 3): FGFR4
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat FGFR4
    6 QIAGEN miScript miRNA Assays for microRNAs that regulate FGFR4:
    hsa-miR-3163 hsa-miR-607 hsa-miR-3613-3p hsa-miR-205* hsa-miR-32* hsa-miR-340
    SwitchGear 3'UTR luciferase reporter plasmid: FGFR4 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for FGFR4 (see all 7)
    OriGene shRNA RFP: FGFR4
    OriGene siRNA: FGFR4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat FGFR4

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for FGFR4

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for FGFR4 (see all 6)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for FGFR4 (see all 4)
    OriGene custom cloning services – gene synthesis, subcloning, mutagenesis, variant library, vector shuttling 
    GenScript: all cDNA clones in your preferred vector (see all 3): FGFR4 (NM_002011)
    Sino Biological Human cDNA Clone for FGFR4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for FGFR4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FGFR4 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for FGFR4
    Search LifeMap BioReagents cell lines for FGFR4

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FGFR4

    Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004713protein tyrosine kinase activity TAS--
    GO:0005007fibroblast growth factor-activated receptor activity IGI10525310
    GO:0005515protein binding ----
    GO:0005524ATP binding IEA--
    GO:0008201heparin binding IDA18480409


    FGFR4 for ontologies           About GeneDecksing


    6 GenomeRNAi human phenotypes for FGFR4:
     Cells with protrusions  Decreased telomerase activity  Increased HPV18 LCR reporter a  Increased cell death HMECs cel 
     Increased cell number in G1, s  Increased gamma-H2AX phosphory 

    Animal Models:
         Mouse knock-out Fgfr4tm1Cxd for FGFR4
         7 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Fgfr4):
     cellular  growth/size  homeostasis/metabolism  mortality/aging  reproductive system 
     respiratory system  tumorigenesis 

    FGFR4 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for FGFR4 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/37 super-pathways (see all 37) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Apoptotic Pathways in Synovial Fibroblasts
    8/13 pathways (see all 13)
    		Apoptotic Pathways in Synovial Fibroblasts1.00
    		ERK5 Signaling0.61
    		p53 Mediated Apoptosis0.84
    		eIF2 Pathway0.60
    		Mitochondrial Apoptosis0.73
    		Rac1 Pathway0.58
    		Telomerase Components in Cell Signaling0.72
    		Nuclear Receptor Activation by Vitamin-A0.57
    2Signaling by FGFR
    8/12 pathways (see all 12)
    		Signaling by FGFR1.00
    		DAP12 signaling0.83
    		Downstream signaling of activated FGFR0.92
    		Signaling by EGFR in Cancer0.83
    		Signaling by FGFR in disease0.91
    		DAP12 interactions0.76
    		Signaling by ERBB20.89
    		Signaling by PDGF0.72
    3PIP3 activates AKT signaling
    8/10 pathways (see all 10)
    		PIP3 activates AKT signaling1.00
    		PI3K/AKT activation0.97
    		PI3K/AKT Signaling in Cancer1.00
    		GAB1 signalosome0.96
    		PI3K events in ERBB2 signaling1.00
    		Constitutive PI3K/AKT Signaling in Cancer0.88
    		PI3K events in ERBB4 signaling1.00
    		Signaling by SCF-KIT0.72
    4IRS-related events
    		IRS-related events1.00
    		Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)0.90
    		IRS-mediated signalling0.98
    		IGF1R signaling cascade0.90
    		Insulin receptor signalling cascade0.94
    		PI3K Cascade0.84
    		IRS-related events triggered by IGF1R0.93
    		Signaling by Insulin receptor0.74
    5GPCR Pathway
    		GPCR Pathway1.00
    		Estrogen Pathway0.55
    		Ras Pathway0.62
    		Pancreatic Adenocarcinoma0.55
    		Breast Cancer Regulation by Stathmin10.58
    		Paxillin Interactions0.53
    		NFAT in Immune Response0.58
    		P2Y Receptor Signaling0.38

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 EMD Millipore Pathway for FGFR4
        Development FGF-family signaling

    5/60 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for FGFR4 (see all 60)
        Nuclear Receptor Activation by Vitamin-A
    Paxillin Interactions
    Telomerase Components in Cell Signaling
    Mitochondrial Apoptosis
    Molecular Mechanisms of Cancer

    2 Cell Signaling Technology (CST) Pathways for FGFR4
        Angiogenesis
    Tyrosine Kinases / Adaptors

    3 Tocris Bioscience Pathways for FGFR4
        Akt Pathway
    Apoptosis Pathway
    NF-kappaB Pathway

    1 GeneGo (Thomson Reuters) Pathway for FGFR4
        Development FGF-family signaling

    2 BioSystems Pathways for FGFR4 
        Regulation of Actin Cytoskeleton
    FGF signaling pathway

    5/47        Reactome Pathways for FGFR4 (see all 47)
        Klotho-mediated ligand binding
    FGFR ligand binding and activation
    Signaling by EGFR in Cancer
    Downstream signal transduction
    IRS-mediated signalling

    1 PharmGKB Pathway for FGFR4
        Vemurafenib Pathway, Pharmacodynamics

    3         Kegg Pathways  (Kegg details for FGFR4):
        MAPK signaling pathway
    Endocytosis
    Regulation of actin cytoskeleton


    FGFR4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for FGFR4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/58 Interacting proteins for FGFR4 (P224553 ENSP000002924084) via UniProtKB, MINT, STRING, and/or I2D (see all 58)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CDH2P190223, ENSP000002691414I2D: score=2 STRING: ENSP00000269141
    FGF4P086203, ENSP000001687124I2D: score=2 STRING: ENSP00000168712
    PLCG1P191743, ENSP000002440074I2D: score=2 STRING: ENSP00000244007
    STAT1P422243, ENSP000003543944I2D: score=2 STRING: ENSP00000354394
    FGF18O760933, ENSP000002746254I2D: score=1 STRING: ENSP00000274625
    About this table

    Gene Ontology (GO): 5/19 biological process terms (GO ID links to tree view) (see all 19):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001759organ induction IEA--
    GO:0008284positive regulation of cell proliferation IGI8663044
    GO:0008286insulin receptor signaling pathway TAS--
    GO:0008543fibroblast growth factor receptor signaling pathway TAS--
    GO:0010715regulation of extracellular matrix disassembly IMP--


    FGFR4 for ontologies           About GeneDecksing



    Drugs & Compounds
    for FGFR4 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    FGFR4 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Compounds for FGFR4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    PD 161570Selective FGFR inhibitor[192705-80-9]
    SU 6668 PDGFR, VEGFR and FGFR inhibitor [252916-29-3]
    SU 5402Potent FGFR and VEGFR inhibitor[215543-92-3]

    2 HMDB Compounds for FGFR4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    1 DrugBank Compound for FGFR4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    PaliferminFGF-7 (see all 5)162394-19-6target--10950949 11149756 9755102 9843417 7526860

    10/11 Novoseek chemical compound relationships for FGFR4 gene (see all 11)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pd 173074 85.8 1 19008009 (1)
    tyrosine 60 27 8576110 (2), 9334263 (1), 7774576 (1), 9010226 (1) (see all 21)
    heparan sulfate 45.3 3 10336501 (1), 8227197 (1), 11278860 (1)
    phosphotyrosine 32.3 1 11830541 (1)
    chenodeoxycholic acid 31.1 1 19085950 (1)
    heparin 29.7 17 7774576 (7), 11278860 (2), 10336501 (1), 10736564 (1) (see all 5)
    phosphatidylinositol 27.5 1 15377668 (1)
    arginine 19.9 13 19918264 (2), 17084840 (1), 18756523 (1), 15448004 (1) (see all 8)
    paraffin 14.5 1 11271786 (1)
    cholesterol 0 3 15750181 (2)

    Search CenterWatch for drugs/clinical trials and news about FGFR4 

    Transcripts
    for FGFR4 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
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    About This Section
    REFSEQ mRNAs for FGFR4 gene (3 alternative transcripts): 
    NM_002011.3  NM_022963.2  NM_213647.1  

    Unigene Cluster for FGFR4:

    Fibroblast growth factor receptor 4
    Hs.165950  [show with all ESTs]
    Unigene Representative Sequence: AB209631
    17 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000292408(uc003mfl.3 uc003mfm.3 uc011dfu.2) ENST00000503708
    ENST00000393648 ENST00000514472 ENST00000502906 ENST00000510911 ENST00000507708
    ENST00000513166 ENST00000393637 ENST00000430285(uc011dfv.1) ENST00000426612(uc003mfn.1)
    ENST00000509511(uc011dfw.1) ENST00000508139 ENST00000511076 ENST00000483872
    ENST00000513423 ENST00000292410(uc003mfo.3)

    miRNA
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    SwitchGear 3'UTR luciferase reporter plasmid: FGFR4 3' UTR sequence
    Inhib. RNA
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    Additional cDNA sequence: 

    AB209631.1 AF202063.1 AF359241.1 AF359246.1 AK225280.1 AK225909.1 AK301169.1 BC011847.2 
    EU826602.1 EU826603.1 L03840.1 M59373.1 X57205.1 

    11 DOTS entries:

    DT.95078845  DT.91981030  DT.100779841  DT.92434632  DT.100042493  DT.120858184  DT.92434636  DT.92434639 
    DT.92434634  DT.100033952  DT.86837266 

    24/182 AceView cDNA sequences (see all 182):

    BM453707 BF969971 BE270306 BM874752 BE501873 NM_213647 BQ899186 BQ690497 
    BC011847 BM743990 AW299662 CA394639 BE671952 BX280999 AI989525 BI115231 
    AF359246 BM740261 AI926324 NM_002011 BQ708634 AA424022 NM_022963 BE205845 

    GeneLoc Exon Structure

    5/13 Alternative Splicing Database (ASD) splice patterns (SP) for FGFR4 (see all 13)    About this scheme

    ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5 ^ 6a · 6b · 6c · 6d ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ·
    SP1:                                -     -                             -                                                                             -         
    SP2:                          -     -     -                             -                                                                             -         
    SP3:                                                                    -                                                                       -               
    SP4:                    -     -     -     -                             -                                                                                       
    SP5:                          -     -                                   -                                                                                       

    ExUns: 12d ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20a · 20b
    SP1:              -                                         -                     
    SP2:              -                                         -                     
    SP3:              -                                         -                     
    SP4:                                                                              
    SP5:                                                                              


    ECgene alternative splicing isoforms for FGFR4

    Expression
    for FGFR4 gene

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    FGFR4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GGGCCCCTGG

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    FGFR4 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/12 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 12) 
    Tissue Anatomical Compartment CellCategory (developmental path)
    BoneZeugopod Epiphyseal EndChondrocytesBone, Cartilage
    BrainChoroid PlexusChoroid Plexus Progenitor CellsChoroid Plexus
    Gut TubeForegutForegut Endoderm CellsEndoderm
    Gut TubeVentral Foregut EndodermVentral Foregut Endoderm CellsEndoderm
    LimbForelimb Muscle Satellite PoolForelimb Muscle Satellite CellsSkeletal Muscle
    LimbForelimb MyotomeLimb Muscle Progenitor CellsSkeletal Muscle
    LimbHindlimb Muscle Satellite PoolHindlimb Muscle Satellite CellsSkeletal Muscle
    LimbHindlimb MyotomeLimb Muscle Progenitor CellsSkeletal Muscle
    Skeletal MuscleCervical Muscle Satellite PoolMuscle Satellite CellsSkeletal Muscle
    Skeletal MuscleHyoid Arch MusclesMononuclear MyocytesSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    Line H1 (WA01) (Embryonic Stem Cell)Early Embryo, Inner Cell Mass

    See FGFR4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for FGFR4

    SOURCE GeneReport for Unigene cluster: Hs.165950

    UniProtKB/Swiss-Prot: FGFR4_HUMAN, P22455
    Tissue specificity: Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell
    lines

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    Orthologs
    for FGFR4 gene

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section
    This gene was present in the common ancestor of animals.

    Orthologs for FGFR4 gene from 6/19 species (see all 19)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves FGFR41 fibroblast growth factor receptor 4 74.57(n)
    72.99(a)    		   395603  XM_003642072.1  XP_003642120.1 
    lizard
    (Anolis carolinensis)    		 Reptilia FGFR46
    		 --
    		 71(a)
    		 1 ↔ 1
    		 2(145256778-145271971)
    African clawed frog
    (Xenopus laevis)    		 Amphibia LOC3977012 FGF receptor 4a 74.14(n)    D31761.1 
    zebrafish
    (Danio rerio)    		 Actinopterygii fgfr41 fibroblast growth factor receptor 4 64.08(n)
    66.36(a)    		   100000160  NM_131430.1  NP_571505.1 
    fruit fly
    (Drosophila melanogaster)    		 Insecta tor3 eggshell pattern formation transmembrane
    receptor more    		 52(a)
    (best of 3)    		   43E12   --
    worm
    (Caenorhabditis elegans)    		 Secernentea ver-23 protein kinase 39(a)
    (best of 16)    		   III(146982-150196)   --


    ENSEMBL Gene Tree for FGFR4 (if available)
    TreeFam Gene Tree for FGFR4 (if available) 

    Paralogs
    for FGFR4 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for FGFR4 gene
    FLT42  PDGFRB2  CSF1R2  FGFR32  KIT2  PDGFRA2  RET2  KDR2  
    FGFR12  FGFR22  FLT32  FLT12  
    18/54 SIMAP similar genes for FGFR4 using alignment to 13 protein entries:     FGFR4_HUMAN (see all proteins) (see all similar genes):
    FGFR-4    BEK    K-SAM    FGFR3    FGFR2    FGFR1
    ABL1    FLT1    RET/PTC2    CCDC6-RETa    CCDC6-RETc    urf-ret
    FLT4    MAPK8    KIT    TXK    EPHA2    FGR

    FGFR4 for paralogs           About GeneDecksing



    Genomic Variants
    for FGFR4 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/385 NCBI SNPs in FGFR4 are shown (see all 385)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 5 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs3518551,2
    		C,F,H,other172600426(-) CAGCCC/TGGCCA 5 R G int1 mis1 ese324Minor allele frequency- G:0.00MN NA NS EA WA EU 5605
    rs765443791,2
    		--171433871(+) TTTAAG/ATCTCT 2 -- us2k11Minor allele frequency- A:0.01NA 120
    rs738067251,2
    		C,--171434167(+) GTGCAC/TCCAGC 2 -- us2k15Minor allele frequency- T:0.08WA CSA NA EA 361
    rs119481271,2
    		C,F,H,--171434214(+) AGAAGG/ACTTGA 2 -- us2k1 trp315Minor allele frequency- A:0.06NS NA WA 1572
    rs455859381,2
    		C,--171434669(+) TGCTAA/GCATGT 2 -- us2k15Minor allele frequency- G:0.01NS 170
    rs31359101,2
    		C,F,--171434676(+) ATGTCT/CACTTT 2 -- us2k19Minor allele frequency- C:0.08NS WA NA EA 530
    rs455576391,2
    		C,F,--171434781(+) GCCTAT/CGACGT 2 -- us2k17Minor allele frequency- C:0.08NS CSA WA 288
    rs455739321,2
    		C,--171434961(+) GGTACG/TTGAAA 2 -- us2k15Minor allele frequency- T:0.01NS 168
    rs31359121,2
    		F,H,--171436438(+) GATCCG/CACTGG 3 -- int1 us2k14Minor allele frequency- C:0.01NS EA 418
    rs31359141,2
    		C,H,--171436846(+) gcgccA/Gttctc 3 -- us2k1 int11Minor allele frequency- G:0.00NA 2

    HapMap Linkage Disequilibrium report for FGFR4 (176513887 - 176525145 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for FGFR4
         1 CNV: 64380
    Human Gene Mutation Database (HGMD): FGFR4

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    Disorders / Diseases
    for FGFR4 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    FGFR4 for disorders           About GeneDecksing

    OMIM gene information: 134935    OMIM disorders: --

    20/57 diseases for FGFR4 (see all 57):    About MalaCards
    achondroplasia    gliomatosis cerebri    soft tissue sarcoma    anaplastic astrocytoma
    cancer progression/metastasis    pituitary adenoma    alveolar rhabdomyosarcoma    oral squamous cell carcinoma
    craniosynostosis    squamous cell carcinoma    breast fibroadenoma    sotos syndrome
    pituitary tumor    craniosynostosis, syndromic    insulin resistance    astrocytoma
    malignant glioma    renal cell carcinoma    cblc    rhabdomyosarcoma

    2 diseases from the University of Copenhagen DISEASES database for FGFR4:
    Cancer     Craniosynostosis

    10/27 Novoseek disease relationships for FGFR4 gene (see all 27)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pituitary tumors 48.7 9 12937159 (3), 12642581 (2), 16857743 (1), 11781352 (1) (see all 5)
    aggressiveness 41.7 4 15448004 (1), 19008009 (1)
    breast cancer 38.9 28 14710228 (3), 20066896 (2), 11549253 (2), 16012724 (2) (see all 15)
    cancer 34.1 33 19240166 (3), 17084840 (1), 17607666 (1), 19946327 (1) (see all 17)
    hnscc 32.6 5 18487077 (2), 15197773 (2)
    adenoma 31.6 9 15070963 (2)
    tumors 30.9 61 15070963 (3), 9740144 (3), 19008009 (3), 11958417 (2) (see all 32)
    pituitary adenoma 28.8 13 15070963 (4), 18070145 (2), 11781345 (1)
    adenocarcinoma lung 25.7 6 17487277 (3), 19296538 (1)
    astrocytoma 24.3 15 8679334 (5), 11958417 (2), 16198476 (1), 15981099 (1)

    Genetic Association Database (GAD): FGFR4
    Human Genome Epidemiology (HuGE) Navigator: FGFR4 (36 documents)
    Tumor Gene Database (TGDB): FGFR4

    Export disorders for FGFR4 gene to outside databases

    Publications
    for FGFR4 gene

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for FGFR4 gene, integrated from 9 sources (see all 272):
    (articles sorted by number of sources associating them with FGFR4)    		    Utopia: connect your pdf to the dynamic
    world of online information

    1. FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. (PubMed id 1709094)1, 2, 9 Partanen J.M.... Alitalo K. (1991)
    2. Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression. (PubMed id 18670643)1, 2, 9 Wang J....Ittmann M.M. (2008)
    3. Genomic structure and complete sequence of the human FGFR4 gene. (PubMed id 9457674)1, 2, 9 Kostrzewa M. and Muller U. (1998)
    4. Fibroblast growth factor receptor 4 is a high affinity receptor for both acidic and basic fibroblast growth factor but not for keratinocyte growth factor. (PubMed id 7680645)1, 2, 9 Ron D.... Tronick S.R. (1993)
    5. Functional FGFR4 Gly388Arg polymorphism predicts prognosis in lung adenocarcinoma patients. (PubMed id 16061909)1, 4, 9 Spinola M....Dragani T.A. (2005)
    6. Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high-grade soft tissue sarcoma. (PubMed id 14601095)1, 4, 9 Morimoto Y....Inoue H. (2003)
    7. Identification of a novel alternative splicing of human FGF receptor 4: soluble-form splice variant expressed in human gastrointestinal epithelial cells. (PubMed id 10631118)1, 2, 9 Takaishi S.... Chiba T. (2000)
    8. The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression. (PubMed id 15448004)1, 4, 9 Wang J....Ittmann M. (2004)
    9. FGFR4 Gly388Arg polymorphism and prognosis of breast and colorectal cancer. (PubMed id 16012724)1, 4, 9 Spinola M....Dragani T.A. (2005)
    10. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. (PubMed id 17623664)1, 2, 9 Kurosu H....Kuro-o M. (2007)

    External Searches for FGFR4 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing FGFR4 gene

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 2264 HGNC: 3691 AceView: FGFR4 Ensembl:ENSG00000160867 euGenes: HUgn2264
    ECgene: FGFR4 Kegg: 2264 H-InvDB: FGFR4

    Other Databases showing FGFR4 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing FGFR4 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for FGFR4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for FGFR4 Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPshttp://egp.gs.washington.edu/data/fgfr4/

    Intellectual Property
    for FGFR4 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		Patent Information for FGFR4 gene:
    Search GeneIP for patents involving FGFR4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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    About This Section

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