BCL11A
Identifiers
Aliases	BCL11A, BCL11A-L, BCL11A-S, BCL11A-XL, BCL11a-M, CTIP1, EVI9, HBFQTL5, ZNF856, B-cell CLL/lymphoma 11A, DILOS, B cell CLL/lymphoma 11A, BAF complex component, BAF chromatin remodeling complex subunit SMARCM1
External IDs	OMIM: 606557 MGI: 106190 HomoloGene: 11284 GeneCards: BCL11A
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p16.1 Start 60,450,520 bp[1] End 60,554,467 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A3.2 Start 24,078,056 bp[2] End 24,174,123 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence Brodmann area 23 middle temporal gyrus postcentral gyrus Region I of hippocampus proper superior frontal gyrus thymus orbitofrontal cortex entorhinal cortex cavity of mouth Top expressed in barrel cortex ganglionic eminence piriform cortex primary motor cortex subiculum medial ganglionic eminence olfactory tubercle Region I of hippocampus proper olfactory bulb nucleus accumbens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity metal ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding protein heterodimerization activity nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity protein kinase binding sequence-specific DNA binding Cellular component cytoplasm nucleoplasm nucleus postsynaptic density Biological process negative regulation of protein homooligomerization negative regulation of neuron projection development regulation of transcription, DNA-templated regulation of dendrite development negative regulation of transcription by RNA polymerase II positive regulation of collateral sprouting protein sumoylation transcription, DNA-templated negative regulation of collateral sprouting positive regulation of neuron projection development negative regulation of axon extension signal transduction positive regulation of transcription by RNA polymerase II neurogenesis negative regulation of dendrite development positive regulation of gene expression negative regulation of dendrite extension negative regulation of neuron remodeling cellular response to L-glutamate negative regulation of branching morphogenesis of a nerve Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 53335 14025 Ensembl ENSG00000119866 ENSMUSG00000000861 UniProt Q9H165 Q9QYE3 RefSeq (mRNA) NM_018014 NM_022893 NM_138553 NM_138559 NM_001363864 NM_001365609 NM_001159289 NM_001159290 NM_001242934 NM_016707 RefSeq (protein) NP_060484 NP_075044 NP_612569 NP_001350793 NP_001352538 NP_001152761 NP_001152762 NP_001229863 NP_057916 Location (UCSC) Chr 2: 60.45 – 60.55 Mb Chr 11: 24.08 – 24.17 Mb PubMed search [3] [4]
Wikidata
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B-cell lymphoma/leukemia 11A is a protein that in humans is encoded by the BCL11A gene.^[5][6][7]

Function

The BCL11A gene encodes for a regulatory C2H2 type zinc-finger protein, that can bind to the DNA. Five alternatively spliced transcript variants of this gene, which encode distinct isoforms, have been reported.^[7] The protein associates with the SWI/SNF complex, that regulates gene expression via chromatin remodeling.^[8]

BCL11A is highly expressed in several hematopoietic lineages, and plays a role in the switch from γ- to β-globin expression during the fetal to adult erythropoiesis transition.^[9]

Furthermore, BCL11A is expressed in the brain, where it forms a protein complex with CASK to regulate axon outgrowth and branching.^[10] In the neocortex, BCL11A binds to the TBR1 regulatory region and inhibits the expression of TBR1.^[11]

Clinical significance

The corresponding Bcl11a 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. In addition, BCL11A has been found to play a role in the suppression of fetal hemoglobin production. Therapeutic strategies aimed at increasing fetal hemoglobin production in diseases such as beta thalassemia and sickle cell anemia by inhibiting BCL11A are currently being explored.^[12][13]

Furthermore, heterozygous de novo mutations in BCL11A have been identified in an intellectual disability disorder, accompanied with global developmental delay and autism spectrum disorder.^[14] These mutations disrupt BCL11A homodimerization and transcriptional regulation.

BCL11A has also been identified as an important gene of interest in type-2 diabetes. Methylation of BCl11A has been hypothesized to contribute to type-2 diabetes risk, while BCL11a loss in a human islet model was demonstrated to result in an increase in insulin secretion.^[15][16]

Interactions

BCL11A has been shown to interact with a number of proteins. BCL11A was initially discovered as a COUP-TFI interacting protein.^[17] In the nucleus, BCL11A forms paraspeckles that co-localize with NONO.^[14] In neurons, BCL11A interacts with CASK to regulate target genes.^[10] Furthermore, BCL11A interacts with the neuron-specific protein TBR1, which is also implicated in intellectual disability and autism spectrum disorder.^[18]

References

Further reading

External links

• BCL11A+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook BCL11A
• Human BCL11A genome location and BCL11A gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.