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FLASH GENE
Symbol BCL11A contributors: mct/pgu - updated : 27-05-2014
HGNC name B-cell CLL/lymphoma 11A (zinc finger protein)
HGNC id 13221
Corresponding disease
IDFH intellectual developmental disorder with persistence of fetal hemoglobin
Location 2p16.1      Physical location : 60.678.302 - 60.780.633
Synonym name
  • ecotropic viral integration site 9
  • zinc finger protein, C2H2 type, coded at ecotropic EVI integration site 9 homolog
  • B-cell CLL/lymphoma 11A
  • COUP-TF-interacting protein 1
  • C2H2-type zinc finger protein
  • zinc finger protein 856
  • Synonym symbol(s) EVI9, CTIP1, KIAA1809, NRG, BCL11A-S, BCL11A-XL, FLJ10173, FLJ34997, BCL11A-L, HBFQTL5, ZNF856
    DNA
    TYPE functioning gene
    STRUCTURE 102.33 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • presence of a conserved CACCC box in promoters 371 bp upstream of the transcriptional start site (position &
  • 8722;371)
    MAPPING cloned Y linked N status provisional
    Map pter - D2S370 - D2SE357 - BCL11A - D2S2198 - D2S2160 - cen
    Physical map
    LOC391375 2 similar to actin VRK2 2p16-p15 vaccinia related kinase 2 FANCL 2p16.1 Fanconi anemia, complementation group L LOC339799 2p16.1 similar to eukaryotic translation initiation factor 3, subunit 5 epsilon, 47kDa; eukaryotic translation initiation factor 3, subunit 5 (epsilon, 47kD); eIF3-epsilon LOC151443 2p16.1 hypothetical LOC151443 LOC151445 2p16.1 similar to IK cytokine; arginine/glutamic acid/aspartic acid repeat containing protein LOC130839 2p16.1 hypothetical gene LOC130839 BCL11A 2p15 B-cell CLL/lymphoma 11A (zinc finger protein) LOC130865 2p16.1 similar to 60S RIBOSOMAL PROTEIN L26 ATP1B3P1 2p13-p15 ATPase, Na+/K+ transporting, beta 3 pseudogene PAPOLG 2p15 poly(A) polymerase gamma REL 2p12 v-rel reticuloendotheliosis viral oncogene homolog (avian) LOC344423 2p16.1 similar to ribosomal protein S12 FLJ32312 2p16.1 hypothetical protein FLJ32312 PEX13 2p16-p14 peroxisome biogenesis factor 13 KIAA1841 2q14 KIAA1841 protein LOC339804 2p16.1 hypothetical gene supported by AK075484; BC014578 AHSA2 2p16.1-p15 AHA1, activator of heat shock 90kDa protein ATPase homolog 2 (yeast) USP34 2p14 ubiquitin specific protease 34 XPO1 2p16 exportin 1 (CRM1 homolog, yeast) LOC391376 2 similar to 60S ribosomal protein L14 (CAG-ISL 7) FLJ13305 2p15 hypothetical protein FLJ13305 CCT4 2p13.3 chaperonin containing TCP1, subunit 4 (delta) C2orf5 2p15 chromosome 2 open reading frame 5 (MURR1) LOC388954 2 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) B3GNT1 2p14 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 FLJ34583 KIAA0903 2p15 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 5946 91.1 835 developmentally restricted to adult erythroid cells 2008 19056937
  • isoform 1 or BCL11A-XL
  • with BCL11A-L differ only in usage of the 3' terminal exon and function similarly in other settings
  • 5 splicing 3958 83.7 773 is found in nuclear paraspeckles 2008 19056937
  • isoform 2 or BCL11A-L
  • with BCL11A-XL differ only in usage of the 3' terminal exon and function similarly in other settings
  • 5 splicing 2358 26.7 243 predominantly localized to the cytoplasm 2008 19056937
  • isoform 3 or BCL11A-S
  • present in cells that actively express gamma-globin and may participate in other aspects of transcriptional regulation within the beta-globin cluster
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
    Nervousbrain   highly
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly Mus musculus
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmegakaryocyte
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticprogenitor cell Mus musculus
    Lymphoid/ImmuneB cell Mus musculus
    Lymphoid/ImmuneT cell Mus musculus
    cell lineage CD34-positive myeloid precursor cells
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    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
  • 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
  • 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
    ANIMAL & CELL MODELS
  • Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype