.. _BCL11A: BCL11A ^^^^^^ .. contents:: :local: General Information ******************* :Full gene name: B-cell CLL/lymphoma 11A (zinc finger protein) :Entrez Gene ID: 53335 :Location: 2p16.1 :Synonyms: BCL11A-S, BCL11A-XL, HBFQTL5, CTIP1, ZNF856, EVI9, BCL11a-M, BCL11A-L :Type: protein-coding User SNPs ********* SNPs given by the user that are near or inside this gene: +----------+---------------+------------+ | SNP | Distance (bp) | Direction | +==========+===============+============+ | rs243021 | 93483 | downstream | +----------+---------------+------------+ .. _BCL11A Gene summary: NCBI Summary ************ This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008] .. _OMIM ID 606557 : http://omim.org/entry/606557 .. _BCL11A OMIM Text: OMIM **** :OMIM ID: `OMIM ID 606557 `_ .. _BCL11A Phenotype: NCBI Phenotypes *************** * Genetic and clinical correlates of early-outgrowth colony-forming units. * Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. * Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. * Twelve type 2 \ ``diabetes``\ susceptibility loci identified through large-scale association analysis. * A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. * Genome-wide association study in German patients with attention deficit/hyperactivity disorder. * NHGRI GWA Catalog * A genome-wide association identified the common genetic variants influence disease severity in beta0-thalassemia/hemoglobin E. .. _BCL11A GO Term: Gene Ontology ************* * regulation of dendrite development * negative regulation of collateral sprouting * hemopoiesis * protein homodimerization activity * positive regulation of collateral sprouting * cytoplasm * protein heterodimerization activity * zinc ion binding * negative regulation of axon extension * transcription corepressor activity * negative regulation of dendrite development * negative regulation of protein homooligomerization * positive regulation of neuron projection development * protein sumoylation * transcription, DNA-dependent * T cell differentiation * nucleus * nucleic acid binding * B cell differentiation * negative regulation of neuron projection development * negative regulation of gene expression * positive regulation of transcription from RNA polymerase II promoter * regulation of transcription, DNA-dependent .. _BCL11A Pathway: KEGG Pathways ************* No pathways found linked to this gene. .. _BCL11A GeneRIF: GeneRIFs ******** * This study indicates a nominal role for JAZF1 and BCL11A variants in type 2 \ ``diabetes``\ susceptibility in African-Americans. [`PMID 22113416`_] * Affinity Capture-MS [`PMID 16147992`_] * the apparent occurrence of an unusual TG 3' splice site in intron 4 is discussed [`PMID 17672918`_] * Observational study of gene-disease association. (HuGE Navigator) [`PMID 21068433`_] * BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body. [`PMID 18681895`_] * Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and genetic testing. (HuGE Navigator) [`PMID 20075150`_] * Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) [`PMID 20379614`_] * The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. [`PMID 11986957`_] * BCL11A binds a core motif in the gamma-globin proximal promoter, recruits and interacts with partners to form a repression complex, leading to deacetylation of histones and down-regulation of gamma-globin transcription. [`PMID 19153051`_] * Reconstituted Complex; Two-hybrid [`PMID 10744719`_] * Genome-wide association study of gene-disease association. (HuGE Navigator) [`PMID 17767159`_] * A novel intronic SNP, rs7606173, associates with F-cell levels in sickle cell patients (P-value <1.81 x 10(-15)). [`PMID 21326311`_] * SIRT1 has a role in transcriptional repression mediated by BCL11A in mammalian cells [`PMID 15639232`_] * Affinity Capture-Western; Reconstituted Complex [`PMID 15639232`_] * Study shows that SNPs in BCL11A were associated with HbF containing erythrocyte numbers in Chinese with beta-thalassemia trait, and with HbF levels in Thais with either beta-thalassemia or HbE trait and in African Americans with sickle cell anemia. [`PMID 18691915`_] * SNPs in BCL11A and the HBS1L-MYB region did not show statistically significant correlations with HbFlevels.This suggests that the BCL11A and HBS1L-MYB loci have a minor effect on HbF level compared to the XmnI QTL in beta-thalassemia intermedia patients. [`PMID 20472475`_] * Positive Genetic [`PMID 22318606`_] * Affinity Capture-Western [`PMID 16091750`_] * Affinity Capture-Western [`PMID 16091750`_] * Affinity Capture-Western [`PMID 16091750`_] * Affinity Capture-Western [`PMID 16091750`_] * Affinity Capture-Western [`PMID 16091750`_] * BCL11A is a potent silencer of fetal hemoglobin. It controls the beta-globin gene cluster in concert with other factors. [`PMID 21157349`_] * Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) [`PMID 20628086`_] * BCL11A is a critical mediator of species-divergent globin switching [`PMID 19657335`_] * Administration of vascular endothelial growth factor (VEGF)-ZFP-TF may be neuroprotective and has potential as a safe and practical approach for management of motor disability in amyotrophic lateral sclerosis (ALS). [`PMID 21864053`_] * BCL11A may not be the target of the 2p13 alterations in cHL(clasical Hodgkins lymphoma),rather REL is. [`PMID 11830502`_] * These results indicate that BCL11A 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. [`PMID 18245381`_] * Affinity Capture-MS [`PMID 21890473`_] * Observational study of gene-disease association, gene-gene interaction, and gene-environment interaction. (HuGE Navigator) [`PMID 20889853`_] * The most abundant isoform BCL11A-XL was DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. [`PMID 16704730`_] * characterize the prevalence of REL, BCL11A, and MYCN gains in a consecutive CLL series at the time of diagnosis; (ii) define the prognostic relevance of REL, BCL11A, and MYCN gains in CLL. [`PMID 20575024`_] * transcriptional silencing of gamma-globin genes by BCL11A involves long-range interactions and cooperation with SOX6 [`PMID 20395365`_] * deregulated Bcl11a cooperates with Nf1 in leukemogenesis [`PMID 18948576`_] * A subset of ALL cases bearing 14q32 LOH showed a down-regulation of miRNA 14q32 clusters linked to the submicroscopic chromosomal deletion. This had an inverse correlation with the expression of their target BCL11a. [`PMID 20578197`_] * Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [`PMID 20183929`_] * BCL11A is intimately involved in the transcriptional regulation of alpha and beta globins and may also regulate and be regulated by GATA-1 as part of a distinct activator or repressor protein complex. [`PMID 20542454`_] * Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes. [`PMID 19369625`_] * frequency of rs4671393(G->A) was relatively high in patients with HbE/[beta]-thalassemia of Guangxi province of China, accompanying with high level of HbF; polymorphism of rs4671393 possibly prevents severe complications in patients with HbE/[beta]-... [`PMID 22258351`_] * through the interaction with Bcl11A, calcium/calmodulin-dependent serine protein kinase plays a role in axonogenesis, which may be related to brain anatomical characteristics in humans [`PMID 20623620`_] * Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator) [`PMID 19020323`_] * down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression; study finds that BCL11A occupies several discrete sites in the beta-globin gene cluster [`PMID 19056937`_] * Data report that Bcl11A downregulates axon branching, and that the expression of DCC and MAP1b, two molecules involved in direction and branching of axon outgrowth, is controlled by Bcl11A-L. [`PMID 19616629`_] * essential functional role of this repressor of transcription in primary mediastinal B-cell lymphoma [`PMID 16871282`_] .. _PMID 22113416: http://www.ncbi.nlm.nih.gov/pubmed/22113416 .. _PMID 16147992: http://www.ncbi.nlm.nih.gov/pubmed/16147992 .. _PMID 17672918: http://www.ncbi.nlm.nih.gov/pubmed/17672918 .. _PMID 21068433: http://www.ncbi.nlm.nih.gov/pubmed/21068433 .. _PMID 18681895: http://www.ncbi.nlm.nih.gov/pubmed/18681895 .. _PMID 20075150: http://www.ncbi.nlm.nih.gov/pubmed/20075150 .. _PMID 20379614: http://www.ncbi.nlm.nih.gov/pubmed/20379614 .. _PMID 11986957: http://www.ncbi.nlm.nih.gov/pubmed/11986957 .. _PMID 19153051: http://www.ncbi.nlm.nih.gov/pubmed/19153051 .. _PMID 10744719: http://www.ncbi.nlm.nih.gov/pubmed/10744719 .. _PMID 17767159: http://www.ncbi.nlm.nih.gov/pubmed/17767159 .. _PMID 21326311: http://www.ncbi.nlm.nih.gov/pubmed/21326311 .. _PMID 15639232: http://www.ncbi.nlm.nih.gov/pubmed/15639232 .. _PMID 18691915: http://www.ncbi.nlm.nih.gov/pubmed/18691915 .. _PMID 20472475: http://www.ncbi.nlm.nih.gov/pubmed/20472475 .. _PMID 22318606: http://www.ncbi.nlm.nih.gov/pubmed/22318606 .. _PMID 16091750: http://www.ncbi.nlm.nih.gov/pubmed/16091750 .. _PMID 21157349: http://www.ncbi.nlm.nih.gov/pubmed/21157349 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 19657335: http://www.ncbi.nlm.nih.gov/pubmed/19657335 .. _PMID 21864053: http://www.ncbi.nlm.nih.gov/pubmed/21864053 .. _PMID 11830502: http://www.ncbi.nlm.nih.gov/pubmed/11830502 .. _PMID 18245381: http://www.ncbi.nlm.nih.gov/pubmed/18245381 .. _PMID 21890473: http://www.ncbi.nlm.nih.gov/pubmed/21890473 .. _PMID 20889853: http://www.ncbi.nlm.nih.gov/pubmed/20889853 .. _PMID 16704730: http://www.ncbi.nlm.nih.gov/pubmed/16704730 .. _PMID 20575024: http://www.ncbi.nlm.nih.gov/pubmed/20575024 .. _PMID 20395365: http://www.ncbi.nlm.nih.gov/pubmed/20395365 .. _PMID 18948576: http://www.ncbi.nlm.nih.gov/pubmed/18948576 .. _PMID 20578197: http://www.ncbi.nlm.nih.gov/pubmed/20578197 .. _PMID 20183929: http://www.ncbi.nlm.nih.gov/pubmed/20183929 .. _PMID 20542454: http://www.ncbi.nlm.nih.gov/pubmed/20542454 .. _PMID 19369625: http://www.ncbi.nlm.nih.gov/pubmed/19369625 .. _PMID 22258351: http://www.ncbi.nlm.nih.gov/pubmed/22258351 .. _PMID 20623620: http://www.ncbi.nlm.nih.gov/pubmed/20623620 .. _PMID 19020323: http://www.ncbi.nlm.nih.gov/pubmed/19020323 .. _PMID 19056937: http://www.ncbi.nlm.nih.gov/pubmed/19056937 .. _PMID 19616629: http://www.ncbi.nlm.nih.gov/pubmed/19616629 .. _PMID 16871282: http://www.ncbi.nlm.nih.gov/pubmed/16871282 .. _BCL11A Pubmed: PubMed Articles *************** *Recent articles:* * Estruch SB et al. "The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function." PLoS One. 2012;7(6):e37963. `PMID 22675500`_ * He Y et al. "Analysis of rs4671393 polymorphism in hemoglobin E/β-thalassemia major in Guangxi Province of China." J Pediatr Hematol Oncol. 2012 May;34(4):323-4. `PMID 22258351`_ * Lin YY et al. "Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK." Nature. 2012 Feb 8;482(7384):251-5. `PMID 22318606`_ * Langberg KA et al. "Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study." J Hum Genet. 2012 Jan;57(1):57-61. `PMID 22113416`_ * Hinney A et al. "Genome-wide association study in German patients with attention deficit/hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet. 2011 Dec;156B(8):888-97. `PMID 22012869`_ * Wagner SA et al. "A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles." Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. `PMID 21890473`_ * Kliem MA et al. "Intramuscular administration of a VEGF zinc finger transcription factor activator (VEGF-ZFP-TF) improves functional outcomes in SOD1 rats." Amyotroph Lateral Scler. 2011 Sep;12(5):331-9. `PMID 21864053`_ * Shaw SY et al. "Genetic and clinical correlates of early-outgrowth colony-forming units." Circ Cardiovasc Genet. 2011 Jun;4(3):296-304. `PMID 21493818`_ * Bhatnagar P et al. "Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients." J Hum Genet. 2011 Apr;56(4):316-23. `PMID 21326311`_ * Bauer DE et al. "Update on fetal hemoglobin gene regulation in hemoglobinopathies." Curr Opin Pediatr. 2011 Feb;23(1):1-8. `PMID 21157349`_ .. _PMID 22012869: http://www.ncbi.nlm.nih.gov/pubmed/22012869 .. _PMID 21890473: http://www.ncbi.nlm.nih.gov/pubmed/21890473 .. _PMID 22113416: http://www.ncbi.nlm.nih.gov/pubmed/22113416 .. _PMID 21493818: http://www.ncbi.nlm.nih.gov/pubmed/21493818 .. _PMID 22258351: http://www.ncbi.nlm.nih.gov/pubmed/22258351 .. _PMID 22675500: http://www.ncbi.nlm.nih.gov/pubmed/22675500 .. _PMID 21157349: http://www.ncbi.nlm.nih.gov/pubmed/21157349 .. _PMID 21864053: http://www.ncbi.nlm.nih.gov/pubmed/21864053 .. _PMID 22318606: http://www.ncbi.nlm.nih.gov/pubmed/22318606 .. _PMID 21326311: http://www.ncbi.nlm.nih.gov/pubmed/21326311 *Top Pubmed articles linked to gene BCL11A matching any search term:* * Orozco G et al. "Sex-specific differences in effect size estimates at established complex trait loci." Int J Epidemiol. 2012 Jul 23;. `PMID 22825589`_ * Cauchi S et al. "European genetic variants associated with type 2 diabetes in North African Arabs." Diabetes Metab. 2012 Mar 29;. `PMID 22463974`_ * Bao XY et al. "Replication study of novel risk variants in six genes with type 2 diabetes and related quantitative traits in the Han Chinese lean individuals." Mol Biol Rep. 2012 Mar;39(3):2447-54. `PMID 21643948`_ * Langberg KA et al. "Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study." J Hum Genet. 2012 Jan;57(1):57-61. `PMID 22113416`_ * Kiefer CM et al. "Distinct Ldb1/NLI complexes orchestrate γ-globin repression and reactivation through ETO2 in human adult erythroid cells." Blood. 2011 Dec 1;118(23):6200-8. `PMID 22010104`_ * Ohshige T et al. "Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese." PLoS One. 2011;6(10):e26911. `PMID 22046406`_ * Pierce BL et al. "Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data." Cancer Causes Control. 2011 Jun;22(6):877-83. `PMID 21445555`_ * Nielsen T et al. "Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release." Diabetologia. 2011 May;54(5):1052-6. `PMID 21267535`_ * de Miguel-Yanes JM et al. "Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms." Diabetes Care. 2011 Jan;34(1):121-5. `PMID 20889853`_ * Klimentidis YC et al. "Ancestry-informative markers on chromosomes 2, 8 and 15 are associated with insulin-related traits in a racially diverse sample of children." Hum Genomics. 2011 Jan;5(2):79-89. `PMID 21296741`_ * Bailey SD et al. "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study." Diabetes Care. 2010 Oct;33(10):2250-3. `PMID 20628086`_ * Voight BF et al. "Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis." Nat Genet. 2010 Jul;42(7):579-89. `PMID 20581827`_ * Talmud PJ et al. "Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study." BMJ. 2010 Jan 14;340:b4838. `PMID 20075150`_ * Schleinitz D et al. "Lack of significant effects of the type 2 diabetes susceptibility loci JAZF1, CDC123/CAMK1D, NOTCH2, ADAMTS9, THADA, and TSPAN8/LGR5 on diabetes and quantitative metabolic traits." Horm Metab Res. 2010 Jan;42(1):14-22. `PMID 19670153`_ * Simonis-Bik AM et al. "Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function." Diabetes. 2010 Jan;59(1):293-301. `PMID 19833888`_ * Schulze MB et al. "Use of multiple metabolic and genetic markers to improve the prediction of type 2 diabetes: the EPIC-Potsdam Study." Diabetes Care. 2009 Nov;32(11):2116-9. `PMID 19720844`_ * Meigs JB et al. "Genotype score in addition to common risk factors for prediction of type 2 diabetes." N Engl J Med. 2008 Nov 20;359(21):2208-19. `PMID 19020323`_ * Staiger H et al. "Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes." PLoS One. 2008 Aug 20;3(8):e3019. `PMID 18714373`_ .. _PMID 22010104: http://www.ncbi.nlm.nih.gov/pubmed/22010104 .. _PMID 20889853: http://www.ncbi.nlm.nih.gov/pubmed/20889853 .. _PMID 22113416: http://www.ncbi.nlm.nih.gov/pubmed/22113416 .. _PMID 21267535: http://www.ncbi.nlm.nih.gov/pubmed/21267535 .. _PMID 19720844: http://www.ncbi.nlm.nih.gov/pubmed/19720844 .. _PMID 22046406: http://www.ncbi.nlm.nih.gov/pubmed/22046406 .. _PMID 20581827: http://www.ncbi.nlm.nih.gov/pubmed/20581827 .. _PMID 20075150: http://www.ncbi.nlm.nih.gov/pubmed/20075150 .. _PMID 19670153: http://www.ncbi.nlm.nih.gov/pubmed/19670153 .. _PMID 22463974: http://www.ncbi.nlm.nih.gov/pubmed/22463974 .. _PMID 20628086: http://www.ncbi.nlm.nih.gov/pubmed/20628086 .. _PMID 21643948: http://www.ncbi.nlm.nih.gov/pubmed/21643948 .. _PMID 19020323: http://www.ncbi.nlm.nih.gov/pubmed/19020323 .. _PMID 21445555: http://www.ncbi.nlm.nih.gov/pubmed/21445555 .. _PMID 22825589: http://www.ncbi.nlm.nih.gov/pubmed/22825589 .. _PMID 18714373: http://www.ncbi.nlm.nih.gov/pubmed/18714373 .. _PMID 21296741: http://www.ncbi.nlm.nih.gov/pubmed/21296741 .. _PMID 19833888: http://www.ncbi.nlm.nih.gov/pubmed/19833888