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FLASH GENE
Symbol DUX4 contributors: mct/npt - updated : 22-09-2014
HGNC name double homeobox, 4
HGNC id 3082
Location 4q35.2      Physical location : 72.631 - 191.013.476
Synonym name
  • double homeobox protein 10
  • double homeobox protein 4/10
  • double homeobox protein DUX10
  • Synonym symbol(s) DUX10, DUX4L
    DNA
    TYPE functioning gene
    SPECIAL FEATURE gene in gene
    text
  • maps within the D4Z4 repeat unit
  • is in fact a retrogene, most likely retrotransposed to a DNA gene from the DUXC mRNA
  • STRUCTURE 1.62 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • DUX4 promoter activity was dependent on a TACAA and GC box
  • a typical initiator sequence (GCACCTG) overlapping with a putative E box upstream of the ORF start codon
  • two enhancers, DUX4 myogenic enhancer 1 (DME1) and DME2 which activate DUX4-fl expression in skeletal myocytes but not fibroblasts
  • MAPPING cloned Y linked N status provisional
    Physical map
    ZFP42 4q35.2 zinc finger protein 42 FLJ25801 4q35.2 hypothetical protein FLJ25801 FLJ36180 4q35.2 hypothetical protein FLJ36180 LOC389250 4 LOC389250 LOC152663 4q35.2 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) LOC285442 4q35.2 similar to mitochondrial translational release factor 1-like LOC391727 4 LOC391727 LOC345156 4q35.2 similar to CG13722-PA LOC391728 4 LOC391728 HSPCAL2 4q35 heat shock 90kDa protein 1, alpha-like 2 LOC389251 4 hypothetical gene supported by BC029568 LOC391729 4 LOC391729 LOC391730 4 similar to apopolysialoglycoprotein - cherry salmon LOC389252 4 LOC389252 FRG1 4q35 FSHD region gene 1 TUBB4Q 4q35 tubulin, beta polypeptide 4, member Q LOC389253 4 LOC389253 LOC389254 4 hypothetical gene supported by NM_033178 LOC391731 4 similar to fetal hypothetical protein LOC391732 4 similar to KIAA0664 protein DUX4 4q35 double homeobox, 4
    regionally located in the partially deleted D4Z4 locus (FSHD)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 1617 - 485 . normally expressed in the male germline . expressed only in FSHMD1a cells and muscles . normally expressed at specific developmental stages and is suppressed in most somatic tissues 2010 21060814
    - splicing - - - in muscles 2010 21060814
  • splice form of DUX4 encoding only the N-terminal portion
  • - - 1574 - 424 - -
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two helix-turn-helix (homeo) domains
  • HOMOLOGY
    Homologene
    FAMILY
  • paired homeobox family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nuclear envelope
    basic FUNCTION
  • involved in regulation of transcription, DNA-dependent
  • DUX4-mediated cell death contributes to the pathogenic pathway in FSHD (Kowaljow 2007)
  • initiates a large transcription deregulation cascade leading to muscle atrophy and oxidative stress, which are FSHMD1A key features
  • role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy
  • expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • transcription activator of PITX1
  • PITX1 protein can further diffuse to additional myonuclei and expand the transcriptional deregulation cascade initiated by DUX4 in FSHMD1A
  • DUX4 might potentially induce proliferation inhibition and G1 phase arrest through upregulation of CDKN1A
  • LMCD1 is a DUX4 partner
  • cell & other
    REGULATION
    repressed by Wnt/CTNNB signaling is important for transcriptional repression of DUX4
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in patient myoblasts at both mRNA and protein level in FSHMD1A, attributable to the stabilized distal DUX4 transcript (
    constitutional     --over  
    induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope (Kowaljow 2007)
    constitutional     --other  
    in FSHMD1A, the combination of inefficient chromatin silencing of the D4Z4 repeat and inappropriate DUX4 protein expression in muscle cells
    tumoral fusion      
    to CIC as a result of a recurrent chromosomal translocation t(4;19)(q35;q13) in Ewing-like sarcomas
    constitutional     --other  
    expressed in FSHMD1A myotubes
    constitutional     --over  
    over ten-fold in FSHMD1A myoblasts and myotubes with short telomeres, and its expression is inversely proportional to telomere length
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS