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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_0022893 4 splicing 5946 NP_075044 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 NM_018014 5 splicing 3958 NP_060484 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 NM_138559 5 splicing 2358 NP_612569 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)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine parathyroid       highly Lymphoid/Immune lymph node       highly   spleen       highly   thymus       highly Nervous brain       highly Reproductive male system testis     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Mus musculus

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic megakaryocyte Blood/Hematopoietic monocyte Blood/Hematopoietic progenitor cell Mus musculus Lymphoid/Immune B cell Mus musculus Lymphoid/Immune T 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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed blood hemoglobin   therapeutic target for reactivation of HbF in beta-hemoglobin disorders neurology acquired   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