BCL3: B-Cell CLL/Lymphoma 3 - Transcriptional Coactivator in NF-κB Signaling
BCL3 (B-Cell CLL/Lymphoma 3) is a proto-oncogene encoding a transcriptional coactivator that modulates NF-κB activity, implicated in hematologic malignancies and immune disorders.
Gene Information Card
| Symbol | BCL3 |
|---|---|
| Full Name | B-Cell CLL/Lymphoma 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 602 ncbi.nlm.nih.gov/gene/602 |
| Ensembl ID | ENSG00000069399 |
| UniProt ID | P20749 |
| OMIM ID | 109560 |
| HGNC ID | 998 |
| Aliases | B-cell leukemia/lymphoma 3, BCL-3, BCL4 |
Description
BCL3 (B-Cell CLL/Lymphoma 3) is a proto-oncogene located on chromosome 19q13.32. It encodes a protein that functions as a transcriptional coactivator and inhibitor of NF-κB transcription factors. BCL3 is involved in the regulation of cell proliferation, apoptosis, and immune responses. Overexpression or mutations of BCL3 are associated with various hematologic malignancies, including chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. The gene is also implicated in inflammatory and autoimmune conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Lymphocytic Leukemia (CLL) | BCL3 overexpression or translocation (e.g., t(14;19)(q32;q13)) leads to constitutive NF-κB activation, promoting B-cell survival and proliferation. | ClinVar, COSMIC, NCBI |
| Multiple Myeloma | BCL3 amplification or aberrant expression enhances NF-κB signaling, contributing to plasma cell malignancy. | COSMIC, NCBI |
| Lymphoma (e.g., diffuse large B-cell lymphoma) | BCL3 rearrangements or overexpression dysregulate NF-κB target genes, driving lymphomagenesis. | COSMIC, NCBI |
| Breast Cancer | BCL3 overexpression is associated with poor prognosis and may promote metastasis via NF-κB pathway activation. | NCBI, COSMIC |
| Inflammatory Bowel Disease (IBD) | BCL3 polymorphisms or altered expression modulate NF-κB-mediated inflammatory responses in gut epithelium. | NCBI, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Low |
| Blood | 6.5 | Low |
| Lung | 4.3 | Low |
| Breast | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| HeLa (cervical cancer) | 8.7 | Medium expression |
| MCF7 (breast cancer) | 6.4 | Low expression |
| HEK293 (embryonic kidney) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Potential loss of start codon, reduced protein expression |
| c.100C>T (p.Arg34Trp) | Missense | <0.1% | Altered protein function, possible gain-of-function |
| t(14;19)(q32;q13) | Translocation | Rare in CLL | BCL3 juxtaposed to IGH enhancer, leading to overexpression |
| Amplification (19q13.32) | Copy number gain | ~2% in multiple myeloma | Increased BCL3 expression, enhanced NF-κB signaling |
Mutation functional classification
Loss of Function (LOF)
Rare missense or truncating mutations (e.g., p.Met1?) that reduce BCL3 protein levels or disrupt its interaction with NF-κB subunits.
Gain of Function (GOF)
Translocations (e.g., t(14;19)) or amplifications leading to BCL3 overexpression, resulting in constitutive NF-κB activation and oncogenic signaling.
Dominant Negative (DN)
Not well-documented; BCL3 typically acts as a coactivator, and dominant-negative effects are not commonly reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-κB signaling pathway (KEGG hsa04064)
• TNF signaling pathway (KEGG hsa04668)
• B cell receptor signaling pathway (KEGG hsa04662)
• Toll-like receptor signaling pathway (KEGG hsa04620)
Protein Summary
The BCL3 protein (UniProt P20749) is a 446-amino acid member of the I-κB family, containing ankyrin repeats that mediate interaction with NF-κB dimers (p50 and p52). Unlike typical I-κB proteins, BCL3 functions primarily as a transcriptional coactivator in the nucleus, enhancing NF-κB-mediated gene expression. It regulates genes involved in cell survival, proliferation, and immune responses. BCL3 is overexpressed in several cancers, particularly B-cell malignancies, where it drives oncogenic NF-κB signaling. The protein also plays roles in inflammation and development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCL3 Knockout HEK293 Cell Line | EDJ-KQ1481 | Human | 602 | Details Get a Quote |
| BCL3 Knockout A-549 Cell Line | EDJ-KQ21066 | Human | 602 | Details Get a Quote |
| BCL3 Knockout HeLa Cell Line | EDJ-KQ21068 | Human | 602 | Details Get a Quote |
| BCL3 Knockout HCT 116 Cell Line | EDJ-KQ19733 | Human | 602 | Details Get a Quote |
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