BCL11B
BCL11 Transcription Factor B: A Key Regulator in T-Cell Development and Neurogenesis
Gene Information Card
| Symbol | BCL11B |
|---|---|
| Full Name | BCL11 Transcription Factor B |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 64919 ncbi.nlm.nih.gov/gene/64919 |
| Ensembl ID | ENSG00000127152 |
| UniProt ID | Q9C0K0 |
| OMIM ID | 606558 |
| HGNC ID | 13222 |
| Aliases | CTIP2, ZNF856B, hRlt1, SMARCM1 |
Description
BCL11B (BCL11 Transcription Factor B) encodes a C2H2-type zinc finger protein that functions as a transcriptional repressor and activator. It is essential for T-cell lineage commitment and differentiation, and plays critical roles in neurogenesis, neuronal migration, and cortical development. BCL11B is also involved in chromatin remodeling through interactions with the NuRD complex and SWI/SNF complexes. Mutations and dysregulation of BCL11B are associated with T-cell acute lymphoblastic leukemia (T-ALL), severe combined immunodeficiency, and neurodevelopmental disorders including intellectual disability and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell acute lymphoblastic leukemia (T-ALL) | Translocations (e.g., t(5;14)(q35;q32)) and deletions disrupt BCL11B expression, leading to aberrant T-cell proliferation and differentiation arrest. | PMID: 17360460, COSMIC |
| Severe combined immunodeficiency (SCID) | Biallelic loss-of-function mutations impair T-cell development, causing T-B+NK+ SCID phenotype. | PMID: 26912624, ClinVar |
| Intellectual disability, autosomal dominant 49 (MRD49) | Heterozygous missense and nonsense mutations in BCL11B disrupt neurogenesis and cortical development, leading to intellectual disability, speech delay, and dysmorphic features. | PMID: 29656859, OMIM #617101 |
| Autism spectrum disorder | De novo loss-of-function variants in BCL11B are associated with ASD, likely due to impaired neuronal migration and synaptic function. | PMID: 29656859, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.3 | Medium |
| Thymus | 8.9 | Medium |
| Cerebral cortex | 6.7 | Low |
| Cerebellum | 5.2 | Low |
| Testis | 4.1 | Low |
| Bone marrow | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.2 | High expression; model for T-ALL |
| MOLT-4 (T-cell leukemia) | 12.8 | High expression |
| K562 (erythroleukemia) | 1.5 | Low expression |
| HeLa (cervical carcinoma) | 0.8 | Very low expression |
| SH-SY5Y (neuroblastoma) | 4.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.169C>T (p.Arg57*) | Nonsense | Rare | Loss of function; truncation of zinc finger domains; associated with MRD49 and SCID |
| c.512G>A (p.Arg171Gln) | Missense | Rare | Loss of function; disrupts DNA binding; associated with intellectual disability |
| t(5;14)(q35;q32) | Translocation | Recurrent in T-ALL | Gain of function?; BCL11B overexpression due to enhancer hijacking; drives leukemogenesis |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein production; associated with SCID |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that impair DNA binding or protein stability lead to haploinsufficiency or complete loss of BCL11B function. These are associated with SCID (biallelic) and neurodevelopmental disorders (heterozygous).
Gain of Function (GOF)
Translocations such as t(5;14)(q35;q32) result in BCL11B overexpression due to juxtaposition with strong enhancers, contributing to T-ALL pathogenesis. No activating point mutations are well-characterized.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg171Gln) may exert dominant-negative effects by forming non-functional dimers or competing with wild-type BCL11B for DNA binding, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T-cell receptor signaling pathway (KEGG hsa04660)
• Notch signaling pathway (KEGG hsa04330)
• Chromatin remodeling by NuRD complex (Reactome R-HSA-212300)
• Transcriptional regulation by BCL11B (PMID: 17360460)
Protein Summary
BCL11B (CTIP2) is a 894-amino acid zinc finger transcription factor that localizes to the nucleus. It contains six C2H2-type zinc finger domains and a proline-rich region. BCL11B interacts with the NuRD complex, SWI/SNF complex, and other transcription factors (e.g., COUP-TF, GATA3) to regulate gene expression. It is critical for T-cell lineage commitment by repressing alternative lineage programs (e.g., NK cell, myeloid) and promoting T-cell differentiation. In the nervous system, BCL11B regulates neuronal migration, axon guidance, and cortical lamination. Its expression is enriched in lymphoid tissues and the brain. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCL11B Knockout HEK293 Cell Line | EDJ-KQ12527 | Human | 64919 | Details Get a Quote |
| BCL11B Knockout HeLa Cell Line | EDJ-KQ57093 | Human | 64919 | Details Get a Quote |
| BCL11B Knockout A-549 Cell Line | EDJ-KQ65605 | Human | 64919 | Details Get a Quote |
| BCL11B Knockout HCT 116 Cell Line | EDJ-KQ74033 | Human | 64919 | Details Get a Quote |
