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FLASH GENE
Symbol FAT4 contributors: mct - updated : 19-12-2022
HGNC name FAT tumor suppressor homolog 4 (Drosophila)
HGNC id 23109
Corresponding disease
HKLLS2 Hennekam lymphangiectasia-lymphedema syndrome 2
VMLDS2 Van Maldergem syndrome 2
Location 4q28.1      Physical location : 126.237.566 - 126.414.086
Synonym name
  • Fat-like cadherin FATJ protein
  • hypothetical protein FLJ23056
    • Synonym symbol(s) CDHF14, FAT-J, FLJ23056, Nbla00548
    DNA
    TYPE functioning gene
    STRUCTURE 176.52 kb     17 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 16114 - 4981 - 2004 15003449
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary   
    Hearing/Equilibriumear    
    Respiratoryrespiratory tracttrachea   
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • localised to progenitors in intermediate regions of the neural tube
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Fat4 (91.4pc)
    Homologene
    FAMILY
    CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • regulates vertebrate planar cell polarity (PCP) and loss of PCP signaling may underlie some cystic diseases in humans
  • strong candidate for a breast tumor suppressor gene
  • FAT4 and DCHS1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex
  • likely acts through the Hippo pathway to regulate cell numbers in specific subsets of neural progenitor pools and their differentiated progeny
  • plays a role in vertebrate planar polarity
  • FAT3 and FAT4 synergize potentially to drive vertebral arch fusion at the dorsal midline during caudal vertebra morphogenesis
  • involved in the maintenance of PCP and inhibition of cell proliferation
  • FAT1 and FAT4 suppress tumor growth via activation of Hippo signaling, whereas FAT1 promotes tumor migration via induction of actin polymerization
  • FAT1 and FAT4 binding coordinates likely distinct pathways at apical junctions to regulate neural progenitor proliferation, neural tube closure and apical constriction
  • FAT4 and DCHS1 establish polarized cell behaviour intrinsically within the mesenchyme
  • FAT4 is a tumor suppressor gene exerting an important role in cell adhesion
  • reduced expression of FAT4 and increased methylation of its promoter may be one of the effective processes in turning a healthy stomach tissue into a tumor tissue
  • FAT4 interacts with RET to fine-tune RET signaling, establishing a juxtacrine mechanism controlling kidney development
  • FAT4 functions in a lymphatic endothelial cell-autonomous manner to control cell polarity in response to flow and is required for lymphatic vessel morphogenesis throughout development
  • has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-transition (EMT) and anti-malignant growth in several cancers
  • FAT4 exhibits a specific domain of expression in the mesenchyme of the medial nasal processes thatform the median upper lip
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • DCHS1-FAT4 is a signalling pathway in osteoblast differentiation
    • a component
  • importance of the FAT4-DCHS1-MPP5 complex in organizing the apical membrane architecture of neural progenitor cells
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
    ions Ca2+ binding
    protein
  • mediates its action via the Hippo pathway mediator YAP1
  • directly interacts with MPDZ/MUPP1 to recruit membrane&
    • 8209;associated guanylate kinase MPP5
  • interaction between the atypical cadherin FAT4 and RET, a tyrosine kinase receptor essential for kidney development
  • FAT4 is a target gene of GATA-binding protein 2 (GATA2), a key transcriptional regulator of lymphatic vascular development and, in particular, lymphatic vessel valve development
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) VMLDS2 , HKLLS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    FAT4 mRNA is repressed in breast cancer and lung cancer due to promoter hypermethylation
    tumoral     --low  
    by promoter methylation was associated in gastric carcinoma with tumor grade, with higher repression at advanced grade
    tumoral     --low  
    promotes increased growth and invasion through the activation of Hippo and WNT-CTNNB1 pathways in ovarian cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Fat4 and Tsc22d1 are likely candidate genes to influence formation of spontaneous pulmonary adenoma in aging male and female mice, respectively