BCL11A Gene: B-Cell CLL/Lymphoma 11A
A key transcription factor in hematopoiesis, neurodevelopment, and hemoglobin switching, implicated in B-cell malignancies and intellectual disability syndromes.
Gene Information Card
| Symbol | BCL11A |
|---|---|
| Full Name | B-cell CLL/lymphoma 11A |
| Gene Type | Protein coding |
| Chromosomal Location | 2p16.1 |
| NCBI Gene ID | 53335 ncbi.nlm.nih.gov/gene/53335 |
| Ensembl ID | ENSG00000119866 |
| UniProt ID | Q9H165 |
| OMIM ID | 606557 |
| HGNC ID | 13221 |
| Aliases | CTIP1, EVI9, ZNF856, BCL11A-L, BCL11A-S, BCL11A-XL |
Description
BCL11A (B-cell CLL/lymphoma 11A) is a zinc-finger transcription factor that plays critical roles in hematopoiesis, neurodevelopment, and immune regulation. It is essential for B-cell development and is a major regulator of fetal hemoglobin (HbF) expression by repressing the gamma-globin genes in adult erythroid cells. BCL11A is also implicated in the pathogenesis of B-cell malignancies, particularly chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), where it acts as an oncogene. Additionally, haploinsufficiency of BCL11A causes a neurodevelopmental disorder characterized by intellectual disability and autism-like features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| B-cell chronic lymphocytic leukemia (CLL) | BCL11A is overexpressed in CLL cells; it promotes cell survival and proliferation through transcriptional regulation of anti-apoptotic genes. | High expression in CLL; knockdown reduces viability (e.g., studies in CLL cell lines). |
| Diffuse large B-cell lymphoma (DLBCL) | BCL11A is amplified/overexpressed in DLBCL, contributing to oncogenic signaling. | Copy number gains and mRNA overexpression in DLBCL cohorts. |
| Intellectual developmental disorder with persistence of fetal hemoglobin (IDPF) | Haploinsufficiency of BCL11A leads to neurodevelopmental defects and elevated HbF levels. | Pathogenic variants (loss-of-function) in BCL11A cause autosomal dominant IDPF. |
| Sickle cell disease (protective modifier) | Reduced BCL11A expression in erythroid cells increases HbF, which ameliorates disease severity. | GWAS and functional studies show BCL11A variants associated with HbF levels. |
| Acute myeloid leukemia (AML) | BCL11A may act as an oncogene in AML, but its role is less defined. | Expression studies show upregulation in some AML cases. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High (e.g., ~30-50 nTPM) | High expression in hematopoietic tissues. |
| Lymph Node | High (e.g., ~20-40 nTPM) | High in lymphoid tissues. |
| Spleen | Moderate (e.g., ~10-20 nTPM) | Moderate expression. |
| Brain | Low (e.g., ~5-10 nTPM) | Low but present in specific regions. |
| Liver | Low (e.g., <5 nTPM) | Low expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | High (e.g., ~50 nTPM) | Erythroleukemia cell line; BCL11A is highly expressed. |
| Raji (Burkitt lymphoma) | High (e.g., ~40 nTPM) | B-cell line; high expression. |
| Jurkat (T-ALL) | Low (e.g., ~5 nTPM) | T-cell line; low expression. |
| HepG2 (liver) | Low (e.g., <5 nTPM) | Low expression. |
| SH-SY5Y (neuroblastoma) | Moderate (e.g., ~10 nTPM) | Neuronal line; moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.835C>T (p.Arg279Ter) | Nonsense | Rare (pathogenic) | Loss-of-function; causes IDPF. |
| c.1000delC (p.Leu334TrpfsTer5) | Frameshift | Rare (pathogenic) | Loss-of-function; causes IDPF. |
| c.2T>C (p.Met1Thr) | Missense (start codon) | Rare (pathogenic) | Loss-of-function; causes IDPF. |
| Amplification of 2p16.1 | Copy number gain | Frequent in DLBCL | Overexpression; oncogenic. |
| c.1234G>A (p.Gly412Arg) | Missense | Rare (uncertain) | Potential dominant-negative effect; reported in neurodevelopmental disorder. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (nonsense, frameshift, splice site) lead to haploinsufficiency, causing IDPF and elevated HbF. In cancer, loss-of-function may also contribute to tumor progression in some contexts.
Gain of Function (GOF)
Gain-of-function is mainly due to gene amplification or overexpression, leading to oncogenic activity in B-cell lymphomas.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative by disrupting protein-protein interactions or DNA binding, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Chromatin binding | • Protein homodimerization activity |
| • Regulation of transcription by RNA polymerase II | • Negative regulation of transcription by RNA polymerase II |
| • Positive regulation of transcription by RNA polymerase II | • Cell differentiation |
| • B cell differentiation | • Hemoglobin switching |
Pathways
• B cell receptor signaling pathway
• Notch signaling pathway (regulation)
• Wnt signaling pathway (regulation)
• Hematopoietic stem cell differentiation
• Erythroid differentiation and hemoglobin switching
Protein Summary
The BCL11A protein is a 835-amino acid zinc-finger transcription factor that contains six C2H2-type zinc fingers and a proline-rich region. It interacts with various chromatin remodeling complexes, including NuRD and SWI/SNF, to regulate gene expression. BCL11A is essential for B-cell development and functions as a repressor of gamma-globin genes in adult erythroid cells. It also plays roles in neuronal development and is implicated in cancer, where it can act as an oncogene or tumor suppressor depending on context.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCL11A Knockout HEK293 Cell Line | EDJ-KQ3754 | Human | 53335 | Details Get a Quote |
| BCL11A Knockout HeLa Cell Line | EDJ-KQ56365 | Human | 53335 | Details Get a Quote |
| BCL11A Knockout A-549 Cell Line | EDJ-KQ64855 | Human | 53335 | Details Get a Quote |
| BCL11A Knockout HCT 116 Cell Line | EDJ-KQ73298 | Human | 53335 | Details Get a Quote |
