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FLASH GENE
Symbol IRF6 contributors: mct/npt/pgu - updated : 03-09-2023
HGNC name interferon regulatory factor 6
HGNC id 6121
Corresponding disease
OFC6 orofacial cleft 6
PPS popliteal pterygium syndrome
VWS van der Woude syndrome
Location 1q32.2      Physical location : 209.961.261 - 209.979.479
Synonym symbol(s) HIRF6, LPS, PIT, OFC6, PPS, PPS1, VWS, VWS1
DNA
TYPE functioning gene
STRUCTURE 20.55 kb     9 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 4505 53 467 - 2005 15939375
7 - 4256 - 372 - 2005 15939375
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 mouth   highly
Nervousbrain    
Reproductivemale systemprostate   
Respiratoryrespiratory tracttrachea  highly
Skin/Tegumentskin appendageshairfollicle  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Epithelialbarrier liningepidermis   Homo sapiens
Epithelialsecretoryglandularexocrine 
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text tooth buds, fusing palate
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal helix-turn-helix DNA binding domain
  • a C-terminal SMAD-IRF binding domain (SMIR) (protein-binding domain)
  • a highly conserved N-terminal, DNA-binding domain and a less well-conserved protein-binding domain (Little 2009)
  • HOMOLOGY
    interspecies ortholog to murine Irf6
    homolog to C.elegans F32B6.8
    intraspecies homolog to IRF4
    Homologene
    FAMILY
  • interferon regulatory transcription factor (IRF) family
  • CATEGORY regulatory , transcription factor , signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • playing a key role in the development of lip and palate, skin, external genitalia
  • functioning as a co-operative transcriptional activator
  • plays a key role in the formation and maintenance of the oral periderm, spatio-temporal regulation of which is essential for ensuring appropriate palatal adhesion
  • IRF6 and the Notch ligand JAG2 function in convergent molecular pathways during oral epithelial differentiation
  • regulates craniofacial development and epidermal proliferation
  • function for IRF6 in suppression of tumorigenesis in stratified epithelia
  • potential tumor suppressor gene in squamous cell carcinomas, acting on a gene network that contributes to the regulation of cancer cell invasiveness and proliferation
  • essential role in epidermal development, is induced in differentiation through a NOTCH1-dependent mechanism and is a primary NOTCH1 target in keratinocytes
  • IRF6 plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue
  • IRF6 and GRHL3 are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS
  • IRF6 is a mediator of TGFB3, which regulates EMT and fusion process during the embryonic palate development
  • RIPK4 and IRF6 function as a cell-intrinsic signaling axis to regulate keratinocyte differentiation
  • IRF6 regulates TFAP2A protein level in epidermal development 3)
  • IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues 3)
  • homeostasis of IRF6 is required for development of the neural tube and associated structures
  • during head and neck development, IRF6 is involved in the structure formation of the oral and maxillofacial regions, and TGFA is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis
  • IRF6 is a transcription factor that is required for craniofacial development and epidermal morphogenesis
  • role for IRF6 in the delivery of adhesion proteins to the cell membrane
  • IRF6 controls the appearance of single cells and colonies, with the latter being less cohesive in its absence
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text involved in palate formation
    PATHWAY
    metabolism
    signaling
  • TFAP2A-IRF6-GRHL3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development
  • likely RIPK4-IRF6 signaling axis plays a multifaceted role in barrier epithelial homeostasis through its regulation of both keratinocyte inflammation and differentiation
  • a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • interacting with SFN for the keratinocyte proliferation-differentiation switch
  • interacting with JAG2 (IRF6 and JAG2 function in convergent molecular pathways during development of the oral ectoderm)
  • OVOL1 is directly bound by IRF6, and its expression is significantly altered in IRF6-depleted differentiating keratinocytes
  • primary NOTCH1 target in keratinocytes, which contributes to the role of this pathway in differentiation and tumour suppression
  • interaction of IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies
  • IRF6 is involved in TGFB3-mediated palatal fusion
  • important role for cytoplasmic IRF6 in regulating the availability or localization of the NME1/2 complex and thus the dynamic behavior of epithelia during lip/palate development
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) VWS , PPS , OFC6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in squamous cell carcinomas
    constitutional       loss of function
    IRF6 deficiency caused defective expression of genes that are involved in the metabolism of lipids and the formation of tight junctions
    constitutional     --over  
    caused exencephaly, a rostral neural tube defect, through suppression of TFAP2A and GRHL3 expression
    Susceptibility
  • to isolated cleft lip and palate
  • Variant & Polymorphism SNP
  • significant correlation between IRF6 rs642961 and non-syndromic cleft lip with or without cleft palate
  • de novo mutations in IRF6, TFAP2A, and ZFHX4 are associated with Orofacial clefts
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Irf6-deficient mice lack the terminally differentiated epidermal layers, leading to an absence of barrier function