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FLASH GENE
Symbol FGFR4 contributors: mct - updated : 21-03-2020
HGNC name fibroblast growth factor receptor 4
HGNC id 3691
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestine   highly
 liver   predominantly Homo sapiens
Lymphoid/Immunespleen   highly
Visualeyelens   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly
cells
SystemCellPubmedSpeciesStageRna symbol
Digestivehepatocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text strongly, in early development in the CNS (habenular nucleus)
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal peptide
  • three Ig-like domains, an acidic region between the first and second Ig loops
  • a single membrane-spanning segment
  • an intracellular split tyrosine-kinase domain
  • a FGFR4-extracellular domain that might potentially neutralize FGF19, containing three immunoglobulin-like domains (D1-D3)(D2 and D3 are involved in ligand binding, and the C-terminus of D3 profoundly determines ligand specificity )
    • HOMOLOGY
    interspecies homolog to murine Fgfr4 (highly)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • fibroblast growth factor receptor subfamily
    • CATEGORY signaling growth factor , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • involved in the development of endoderm derivatives and in skeletal muscle formation
  • playing a role in the cascade of molecular events leading to terminal muscle differentiation
  • functions in a distinctly different manner than the prototype FGFR during myogenic differentiation
  • required for effective muscle regeneration through a MYOD1-TEAD2-FGFR4 transcriptional pathway
  • regulates bile acid synthesis by repression of CYP7A1 expression
  • may contribute to the repression of bile acid synthesis through JNK signaling but is not required for activation of JNK signaling by bile acids
  • contributes significantly to hepatocellular carcinoma progression by modulating AFP secretion, proliferation and anti-apoptosis
  • plays important roles in negatively regulating hepatic bile acid synthesis and positively regulating hepatic steatosis induced by high fat diet
  • KLB/FGFR4 partnership that mediates endocrine control of hepatic metabolism plays a role in cellular homeostasis and hepatoma suppression through negative control of cell population growth mediated by pro-apoptotic signaling
  • plays a crucial role in the regulation of hepatic bile acid and lipid metabolism
  • pivotal role of FGFR4 in tumor-stroma interactions during colorectal cancer metastasis
  • FGFR4 played a pivotal role in proliferation, invasion and EMT of cholangiocarcinoma (CCA)
  • role of FGF23/FGFR4 signaling in the regulation of cardiac remodeling and function
  • FGF receptors FGFR3, FGFR4 control alveolar elastogenesis
  • FGFR4 plays a critical role in cancer progression and metastasis, particularly in those cancer patients who have FGF19 amplification
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • FGF19-FGFR4 signaling is implicated in many cellular processes including cell proliferation, migration, metabolism, and differentiation
    • a component
  • MMP14/FGFR4 membrane complex that either stimulates or suppresses MMP14 and FGFR4 activities, depending on a tumor progression-associated polymorphism in FGFR4
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CYP7A1
  • KLB is a novel FGFR4 coreceptor required for FGF19 liver specific functions
  • interacts with cell-adhesion receptors such as N-cadherin
  • interacting with FGF19 (FGFR4 activation is the mechanism whereby FGF19 can increase hepatocyte proliferation and induce hepatocellular carcinoma formation)
  • KLB-FGFR4 partnership caused a depression of activated AKT1 and mammalian target of rapamycin while activating ERK1/2 that may underlie the pro-apoptotic effect
  • FGF23 promotes left ventricular hypertrophy (LVH by activating FGFR4
  • FOXC1 promotes colorectal cancer metastasis through transactivating ITGA7 and FGFR4 expression
  • interaction between FGF19 and FGFR4 plays an essential role in colorectal tumorigenesis
    • cell & other
    REGULATION
    activated by FGF19
    Other expression in liver is decreased by fasting and increased by insulin
    ASSOCIATED DISORDERS
    corresponding disease(s) DUP5QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in pancreatic cancer (mediated by an intronic enhancer activated by HNF1alpha)
    tumoral     --over  
    in lung carcinoma
    tumoral     --over  
    in all epithelial carcinomas
    tumoral       gain of function
    in several solid tumors including hepatocellular carcinoma (HCC), breast cancer, oropharyngeal squamous cell carcinoma (OPSCC), and pancreatic cancer (
    Susceptibility
  • to cancer invasion
  • to hepatocellular carcinoma coupled with liver cirrhosis
    • Variant & Polymorphism other
  • Gly388Arg polymorphism most likely contributes to susceptibility to cancer
  • -R388 risk variant is a unique inducer of MMP14 and collagen invasion
  • polymorphism in FGFR4 rs351855 may be associated with the risk of HCC coupled with liver cirrhosis
    • Candidate gene for limb malformation in terminal del5q patients
    Marker
  • is a potential prognostic marker for colorectal cancer
    • Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD)
    cancerdigestiveliver
    frequent overexpression in patients renders its inhibition a novel and much needed pharmacological approach against hepatocellular carcinoma
    cancerreproductivebreast
    targeting FGFR4 in breast cancer cells overexpressing FGF19 may represent an effective strategy to suppress cancer development, progression, and metastasis
    cancerdigestivecolon
    therapeutic marker for colorectal cancer
    ANIMAL & CELL MODELS
  • Fgfr4-deficient mice exhibit an elevated bile acid synthesis due to the upregulation of CYP7A1 in the liver, indicating that activation of hepatocyte FGFR4 negatively regulates bile acid synthesis