Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ASXL1 contributors: mct - updated : 29-11-2016
HGNC name additional sex combs like 1 (Drosophila)
HGNC id 18318
Corresponding disease
BOPS Bohring-Opitz syndrome
Location 20q11.21      Physical location : 30.946.146 - 31.027.121
Synonym name
  • additional sex combs-like protein 1
  • polycomb group protein ASXL1
    • Synonym symbol(s) KIAA0978, MGC117280, MGC71111
    DNA
    TYPE functioning gene
    STRUCTURE 80.98 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1084 - 85 - 2015 26470845
    13 - 7056 165.3 1541 - 2015 26470845
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Blood / hematopoieticplasma  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N- terminal homology domain
  • interaction domains for nuclear receptors
  • ASXN and ASXM domains
  • an HP1-binding motif, critical for retinoic acid receptor repression
  • a C-terminal plant homeodomain protein-protein interaction domain
    • HOMOLOGY
    interspecies homolog to drosophila Asxl
    intraspecies homolog to ASXL2
    Homologene
    FAMILY
  • Asx family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • regulating transcription in a DNA-dependent manner
  • might play the role of a tumour suppressor in myeloid malignancies
  • needed for normal hematopoiesis
  • ccoperates with CBX5 to modulate KDM1A activity leading to RAR repression
  • functions as either a coactivator or corepressor for the retinoid receptors retinoic acid receptor (RAR) and retinoid X receptor in a cell type-specific manner
  • suppresses the transactivation activity of ligand-bound PPARG, as well as its adipocyte differentiation-inducing activity
  • ASXL1 and ASXL2 reciprocally regulate adipogenesis
  • ASXL1 acts as a corepressor in PPAR-mediated transcription, whereas ASXL2 acts as a coactivator
  • importance of ASXL1 in Polycomb group function, development, and hematopoiesis
  • reciprocal role of the ASXL1, ASXL2 in lipid homeostasis through the opposite regulation of NR1H3
  • ASXL2 and ASXL1, two homologous chromatin factors, are novel regulators of heart development
  • pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and chronic myelomonocytic leukemia (CMML), respectively
  • ASXL1 is implicated in the maintenance of podocyte structure via its association with WTIP and in the regulation of WT1 signaling during early kidney development
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CBX5 and KDM1A to repress RAR-mediated transcription
  • BAP1 is a nuclear deubiquitinase known to target histones (together with ASXL1 as a Polycomb repressor subunit) and the HCFC1 transcriptional co-factor
  • SOX2 directly transactivates the ASXL1 promoter, and ASXL1 may be a direct target of SOX2 and may play a role in maintaining the pluripotency of stem cells
  • ASXL1 suppressed ligand-induced NR1H3 transcriptional activity
  • ASXL1 and ASXL2 use their ASXM domains to interact with the C-terminal domain (CTD) of BAP1, and these interactions are required for ubiquitin binding and HIST2H2AC deubiquitination
  • ASXL1-mediated HIST2H2AC deubiquitylation and transcriptional activation of CDKN2B expression are linked to its tumor suppressor functions
  • BAP1 is activated by ASXL1 to deubiquitinate mono-ubiquitinated HIST2H2AC
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BOPS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with PAX5, in t(9;20)(p11-13;q11) in patients with acute lymphoblastic leukemia
    tumoral   deletion    
    with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis
    tumoral somatic mutation      
    associated with CSF3R and/or SETBP1 mutation in chronic neutrophilic leukemia (CNL)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Asxl1 knockout mice exhibit defects in frequency of differentiation of lymphoid and myeloid progenitors, but not in multipotent progenitors
  • Asxl1 deletion in mice led to developmental abnormalities including dwarfism, anophthalmia, and 80% embryonic lethality