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FLASH GENE
Symbol BCL11A contributors: mct/pgu - updated : 27-05-2018
HGNC name B-cell CLL/lymphoma 11A (zinc finger protein)
HGNC id 13221
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six C2H2 type zinc finger domains
  • a proline-rich region
  • a third zinc finger motif
  • an acidic domain
  • a signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Bcl11a (99.5pc)
    homolog to rattus Bcl11a (99.2pc)
    intraspecies homolog to BCL11B
    Homologene
    FAMILY
    CATEGORY DNA associated , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • EVIA in the nucleus, colocalizing with BCL6
  • EVIC in the cytoplasm, colocalizing with BCL6
  • EVIA in the nucleus, colocalizing with BCL6
  • colocalizing with SUMO1 and SENP2 in nuclear speckles
  • basic FUNCTION
  • acting as a transcriptional repressor
  • involved in lymphoid malignancies through either chromosomal translocation or amplification
  • playing a direct role in globin gene regulation
  • might influence globin gene expression either directly by interacting with cis-regulatory elements within the beta-globin cluster or indirectly by affecting cell cycle or other pathways that ultimately impinge on HbF expression
  • may function as a modulator of the transcriptional repression activity of ARP1
  • functioning as a myeloid and B-cell proto-oncogene
  • central mediator of gamma-globin silencing and hemoglobin switching
  • repressor of gamma-globin gene expression in adult erythroid progenitors
  • is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination
  • critical modulator of hemoglobin switching and HbF silencing
  • essential functions of BCL11A in neuronal morphogenesis and sensory wiring of the dorsal spinal cord and FRZB, a component of the WNT pathway, is a downstream acting molecule involved in this process
  • important role for the KLF1-BCL11A axis in erythroid maturation and developmental regulation of globin expression
  • transcription factor known to regulate lymphoid and erythroid developmen
  • MYB and BCL11A cooperate with DNMT1 to achieve developmental repression of embryonic and fetal beta-like globin genes in the adult erythroid environment
  • both BCL11A and MIPEP were associated with increased endogenous levels of HbF
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • binding LCR, epsilon-globin and the intergenic regions between gamma-globin and delta-globin and reconfiguring the beta-globin cluster by modulating chromosomal loop formation
  • RNA
    small molecule
    protein
  • BCL6 for EVI9A (in monocytic differentiation and maintenance) and EVI9B
  • GATA1 specifically associates with BCL11A in erythroid cells
  • interacting with TFCOUP1, PIAS3, ARP1 and EAR2
  • interacting with SOX6 during erythroid maturation nad cooperating in silencing gamma-globin transcription in adult erythroid progenitors
  • interacting witrh KLF1 (KLF1 may control BCL11A expression by both direct and indirect mechanisms)
  • is a novel NR2E1 coregulator that might be involved in NR2E1-dependent gene regulation in the brain
  • is essential for lymphopoiesis and negatively regulates TP53 activities
  • KDM1A/RCOR1 histone demethylase complex interacts with BCL11A and is required for full developmental silencing of gamma-globin genes in adult erythroid cells
  • required for expression of I7 receptor (IL7RA) and FLT3 in early hematopoietic progenitor cells
  • KLF1 regulates BCL11A, a known repressor of adult gamma-globin expression
  • BCL11A may mediate Schwann cell activity through binding to the promoter of nuclear receptor subfamily 2 group F member 2 (NR2F2) and regulating NR2F2 expression
  • cell & other
    REGULATION
    activated by KLF1 (BCL11A expression is activated by KLF1, leading to HBG1, HBG2 repression)
    Other sumoylated by SUMO1
    ASSOCIATED DISORDERS
    corresponding disease(s) IDFH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with REL in B cell lymphoma in t(2;14) (p13;q32.3)
    tumoral     --over  
    in leukemia through inhibition of monocyte differentiation
    constitutional     --low  
    in primary adult erythroid cells leads to robust HbF expression
    Susceptibility to persistance of fetal hemoglobin
    Variant & Polymorphism SNP , other
  • QTL influencing the risk of fetal hemoglobin
  • variants, by modulating HbF levels, act as an important ameliorating factor of the beta-thalassemia phenotype, and it is likely they could help ameliorate other hemoglobin disorders
  • polymorphisms or SNP associated with fetal hemoglobin levels and pain crises in sickle cell disease
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    bloodhemoglobin 
    therapeutic target for reactivation of HbF in beta-hemoglobin disorders
    neurologyacquired 
    potential therapeutic target for the treatment of peripheral nerve injury
    ANIMAL & CELL MODELS
  • Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype