BCL11A

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

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

OMIM ID:`OMIM ID 606557 `_

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.

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

KEGG Pathways

No pathways found linked to this gene.

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]

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

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