# BCL6 Gene: Structure, Function, and Clinical Significance ## Key Takeaways - BCL6 is a master transcriptional repressor essential for the germinal center (GC) reaction, orchestrating B-cell differentiation by repressing genes involved in cell cycle arrest, apoptosis, and terminal differentiation. - Dysregulation of BCL6, primarily through chromosomal translocations (e.g., t(3;14)(q27;q32) with IGH) and somatic hypermutation disrupting its autoregulatory loop, leads to constitutive overexpression in B-cell lymphomas like DLBCL and FL. - The BCL6 protein possesses a modular structure with an N-terminal BTB/POZ domain for dimerization and corepressor recruitment (NCOR1/SMRT/BCOR) and a C-terminal zinc finger domain for sequence-specific DNA binding (consensus: 5'-TTCCTACGAA-3'). - Therapeutic strategies target BCL6's function, with advanced small-molecule inhibitors focusing on blocking the BTB domain's corepressor binding groove, thereby reactivating target genes and inducing lymphoma cell apoptosis. - Beyond oncology, BCL6 plays critical roles in T-cell biology (Tfh cell development), autoimmune diseases (e.g., SLE), inflammatory responses, and metabolic regulation, highlighting its broad physiological significance. --- ## Executive Summary & Key Metadata The BCL6 (B-Cell Lymphoma 6) gene encodes a master transcriptional repressor that is indispensable for the germinal center (GC) reaction, a critical step in T-cell-dependent humoral immunity. BCL6 orchestrates the differentiation of B cells into high-affinity antibody-producing plasma cells and memory B cells by repressing genes involved in cell cycle arrest, apoptosis, and terminal differentiation. Its expression is tightly regulated; however, chromosomal translocations, somatic hypermutation, and epigenetic dysregulation frequently lead to its constitutive overexpression in B-cell lymphomas, most notably diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Beyond oncology, BCL6 is implicated in T-cell biology, inflammation, and metabolic regulation. This reference manual provides a comprehensive, biophysically detailed examination of the BCL6 gene, from its genomic architecture and 3D protein structure to its signaling networks, pathogenic mutations, and therapeutic targeting. | **Attribute** | **Detail** | | :--- | :--- | | **HGNC Symbol** | BCL6 | | **UniProt Accession** | P41182 | | **Representative PDB ID** | true (e.g., 1R28, 2EN2, 3BIM, 4CP3) | | **Chromosomal Locus** | 3q27.3 (GRCh38: chr3:187,721,377-187,745,468) | | **Primary Molecular Function** | Sequence-specific DNA-binding transcription repressor (POZ/BTB and C2H2 zinc finger domains) | | **Disease & Pathology Associations** | Diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma, Hodgkin lymphoma, autoimmune diseases, and inflammatory conditions | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Chromosomal Location and Gene Structure The human *BCL6* gene is located on the long arm of chromosome 3 at band q27.3 (3q27.3). The reference genome (GRCh38) places the gene between base pairs 187,721,377 and 187,745,468 on the forward strand. The gene spans approximately 24 kilobases (kb) of genomic DNA and contains 10 exons, with the translational start site (ATG) located in exon 2 and the stop codon in exon 10. The intron-exon boundaries are highly conserved among mammals, reflecting the critical regulatory and structural constraints of the encoded protein. The genomic organization is complex, featuring a large 5' untranslated region (UTR) and a highly conserved promoter region that lacks a canonical TATA box. Instead, transcription initiation is driven by a TATA-less promoter enriched in GC content, which is characteristic of housekeeping and developmentally regulated genes. This promoter contains multiple binding sites for transcription factors, including SP1, AP-1, and NF-κB, which integrate signals from B-cell receptor (BCR) activation, CD40 signaling, and cytokine stimulation. ### 1.2 Promoter Architecture and Regulatory Elements The *BCL6* promoter is a paradigm of multi-layered transcriptional control. It contains a canonical interferon-stimulated response element (ISRE) and a STAT-binding site, allowing for direct regulation by interferons and interleukins. However, the most critical regulatory element is the **autoregulatory loop** mediated by BCL6 itself. BCL6 binds to its own promoter at two high-affinity sites, repressing its own transcription. This negative feedback loop is essential for the timely exit of B cells from the germinal center reaction. Disruption of this autoregulation is a common oncogenic event. Chromosomal translocations, such as the t(3;14)(q27;q32) involving the immunoglobulin heavy chain (IGH) locus, place the *BCL6* coding exons under the control of the highly active IGH enhancer, leading to constitutive expression. Additionally, somatic hypermutation (SHM) frequently targets the 5' regulatory region of *BCL6*, introducing point mutations that abrogate BCL6 binding to its own promoter, thereby relieving autoregulation and causing overexpression. ### 1.3 Alternative Splicing and Isoforms Alternative splicing of *BCL6* generates multiple mRNA transcripts and protein isoforms. The canonical full-length protein, isoform 1, is 706 amino acids long. However, several splice variants have been characterized: - **Isoform 2 (ΔN-BCL6):** This variant lacks a portion of the N-terminal BTB/POZ domain due to alternative splicing of exon 2. It retains the DNA-binding zinc finger domains but loses the ability to interact with corepressors like NCOR1/2 and SMRT. This isoform acts as a dominant-negative, competing with full-length BCL6 for DNA binding without repressing transcription. - **Isoform 3 (ΔC-BCL6):** A C-terminally truncated variant that lacks the zinc finger domains. This isoform is predominantly cytoplasmic and may have a dominant-negative effect on BCL6-mediated repression. - **Isoform 4:** A variant with an alternative 3' UTR, which affects mRNA stability and translational efficiency. The differential expression of these isoforms is cell-type and context-dependent. In normal GC B cells, the full-length isoform predominates. In certain lymphomas, aberrant splicing can shift the balance toward dominant-negative isoforms, although the full-length oncogenic form remains the primary driver of lymphomagenesis. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Primary Structure and Domain Organization The BCL6 protein (UniProt P41182) is a 706-amino-acid, multi-domain transcription factor. Its architecture is modular, comprising three principal functional domains: 1. **N-terminal BTB/POZ Domain (aa 1-129):** The Broad-Complex, Tramtrack, and Bric-à-brac (BTB) domain, also known as the POZ (Poxvirus and Zinc finger) domain, is a highly conserved protein-protein interaction module. 2. **Central Repression Domain (RD2) (aa 300-400):** A second, less well-defined repression domain that also recruits corepressor complexes. 3. **C-terminal DNA-Binding Domain (aa 518-706):** A tandem array of six C2H2-type zinc finger motifs that mediate sequence-specific DNA recognition. ### 2.2 The BTB/POZ Domain: A Dimerization and Corepressor Docking Site The BTB/POZ domain is the primary structural and functional hub of BCL6. X-ray crystallographic studies (e.g., PDB: 1R28) have revealed that this domain forms a tightly intertwined homodimer. The dimerization interface is extensive, burying a large solvent-accessible surface area and creating a stable, "V-shaped" homodimer. This dimerization is a prerequisite for high-affinity DNA binding and transcriptional repression. The BTB domain also contains a hydrophobic groove on its surface that serves as a docking site for corepressor proteins. BCL6 recruits the corepressors NCOR1, NCOR2 (SMRT), and BCOR through a conserved BCL6-binding motif (BBD) present in these proteins. The interaction is mediated by a short, amphipathic helix from the corepressor that inserts into the hydrophobic groove of the BTB domain. This interaction is critical for BCL6's repressive function, as it recruits histone deacetylases (HDACs) to the target gene promoters. **Structural Insight:** The BTB domain's hydrophobic groove is a validated drug target. Small molecules that bind to this groove, such as the peptidomimetic inhibitor RI-BPI, sterically block the interaction between BCL6 and its corepressors, thereby abrogating its repressive function. This structural vulnerability is the basis for a major class of BCL6-targeted therapies. ### 2.3 The Central Repression Domain (RD2) The RD2 domain is less structurally characterized but is functionally important. It also recruits corepressor complexes, including NCOR1 and SMRT, albeit through a different mechanism than the BTB domain. The RD2 domain is also a target for post-translational modifications, including phosphorylation and acetylation, which modulate its repressive activity. ### 2.4 The C-Terminal Zinc Finger DNA-Binding Domain The C-terminal region contains six C2H2-type zinc finger motifs (ZF1-ZF6). Each finger adopts a classic ββα fold, coordinating a single zinc ion through two cysteine and two histidine residues. These fingers are arranged in a tandem array that wraps around the major groove of DNA, recognizing a specific 10-base-pair consensus sequence: **5'-TTCCTACGAA-3'** (and its variants). The zinc finger domain is essential for target gene recognition. Structural studies (e.g., PDB: 2EN2) have shown that fingers 3-5 make the primary base-specific contacts, while fingers 1, 2, and 6 contribute to binding affinity and specificity. The DNA-binding domain is also a site for oncogenic mutations. Missense mutations within the zinc fingers can either abolish DNA binding (loss-of-function) or alter target gene specificity, contributing to lymphomagenesis. ### 2.5 Post-Translational Modifications and Structural Dynamics BCL6 is heavily post-translationally modified, which regulates its stability, localization, and activity: - **Phosphorylation:** Phosphorylation by MAP kinases (e.g., ERK) at serine 333 and serine 343 within the RD2 domain creates a docking site for the E3 ubiquitin ligase FBXO11, leading to ubiquitination and proteasomal degradation. This is a critical mechanism for terminating BCL6 expression during B-cell differentiation. - **Acetylation:** Acetylation by p300/CBP at lysine residues in the zinc finger domain inhibits DNA binding, providing another layer of negative regulation. - **SUMOylation:** SUMOylation at lysine residues in the BTB domain can modulate its repressive activity. These modifications induce conformational changes that alter protein-protein interactions, DNA binding affinity, and subcellular localization, making BCL6 a highly dynamic and responsive regulator. > **[Interactive 3D Protein Visualizer: Load BCL6 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=P41182)** > > Explore the 3D structure of the BCL6 protein. The visualizer will load the BTB/POZ domain dimer (e.g., PDB: 1R28) and the zinc finger DNA-binding domain (e.g., PDB: 2EN2). You can rotate the molecule, highlight key domains, and visualize the corepressor binding groove. --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 The Germinal Center Reaction and B-Cell Fate BCL6 is the master transcriptional regulator of the germinal center (GC) reaction. Upon antigen encounter, naive B cells are activated and migrate to secondary lymphoid organs, where they form GCs. Within the dark zone of the GC, B cells undergo rapid clonal expansion and somatic hypermutation (SHM) of their immunoglobulin genes. B cells then migrate to the light zone, where they are selected for high-affinity antigen binding. BCL6 is essential for this entire process. BCL6 exerts its function by repressing a large panel of target genes that would otherwise promote cell cycle arrest, apoptosis, or terminal differentiation. Key targets include: - **Cell Cycle Checkpoints:** *CDKN1A* (p21), *CDKN1B* (p27), and *TP53*. By repressing these genes, BCL6 allows for the rapid, unchecked proliferation of GC B cells. - **Apoptosis:** *TP53*, *BIM* (BCL2L11), and *GADD45A*. BCL6 protects GC B cells from DNA damage-induced apoptosis, which is critical given the high rate of SHM. - **Differentiation:** *PRDM1* (BLIMP-1), *IRF4*, and *XBP1*. These are master regulators of plasma cell differentiation. BCL6 represses them to maintain the GC B-cell phenotype and prevent premature exit from the GC. ### 3.2 Corepressor Complexes and Epigenetic Regulation BCL6 does not function alone. It recruits a multi-protein corepressor complex to its target gene promoters. The core complex includes: - **NCOR1/NCOR2 (SMRT):** These scaffold proteins bridge BCL6 to HDACs. - **HDAC1/HDAC2:** These enzymes deacetylate histone tails, leading to chromatin compaction and transcriptional repression. - **BCOR (BCL6 Corepressor):** A dedicated corepressor that recruits the Polycomb repressive complex 1 (PRC1), leading to H2AK119 ubiquitination and further chromatin silencing. - **CTBP1/CTBP2:** C-terminal binding proteins that also contribute to repression. The recruitment of these complexes establishes a repressive chromatin state at BCL6 target genes, characterized by histone H3K27 deacetylation and H3K9 methylation. ### 3.3 Signaling Pathways Regulating BCL6 Expression BCL6 expression is tightly controlled by upstream signaling pathways: - **BCR Signaling:** Antigen engagement of the BCR activates NF-κB, which directly represses *BCL6* transcription. This is a key mechanism for terminating the GC reaction. - **CD40 Signaling:** CD40 ligand (CD40L) on T follicular helper (Tfh) cells engages CD40 on GC B cells, also activating NF-κB and repressing *BCL6*. - **IL-21 Signaling:** IL-21, produced by Tfh cells, activates STAT3, which can either activate or repress *BCL6* depending on the cellular context. In early GC B cells, STAT3 can cooperate with BCL6 to promote the GC phenotype. - **BCL6 Autoregulation:** As mentioned, BCL6 represses its own promoter, creating a negative feedback loop. ### 3.4 Protein-Protein Interaction Networks BCL6 is a hub in a complex protein-protein interaction network. Beyond corepressors, it interacts with: - **Transcription Factors:** Interacts with IRF4, IRF8, and PAX5 to co-regulate target genes. - **Chromatin Remodelers:** Interacts with SWI/SNF complexes to modulate chromatin accessibility. - **E3 Ubiquitin Ligases:** FBXO11 and SPOP target BCL6 for ubiquitin-mediated degradation. - **Histone Methyltransferases:** Interacts with EZH2 (PRC2) to promote H3K27me3. These interactions are context-dependent and dynamically regulated, allowing BCL6 to integrate diverse signals and orchestrate complex transcriptional programs. ```mermaid sequenceDiagram participant APC as "Antigen-Presenting Cell" participant B as "Naive B Cell" participant T as "T Follicular Helper Cell" participant GC as "Germinal Center B Cell" participant PC as "Plasma Cell" APC->>B: Presents Antigen B->>B: BCR Activation B->>T: MHC-II-TCR Interaction T->>B: CD40L & IL-21 B->>B: Upregulation of BCL6 B->>GC: Differentiation into GC B Cell GC->>GC: BCL6 Represses p53, p21, BLIMP-1 GC->>GC: Rapid Proliferation & SHM GC->>GC: BCL6 Autoregulation (Negative Feedback) Note over GC: BCR/CD40 Signaling Activates NF-κB NFkB->>GC: Represses BCL6 Transcription GC->>GC: BCL6 Protein Degradation (FBXO11) GC->>PC: Differentiation into Plasma Cell ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Mechanisms of BCL6 Dysregulation in Lymphoma BCL6 is a proto-oncogene, and its dysregulation is a hallmark of several B-cell lymphomas. The primary mechanisms of dysregulation are: 1. **Chromosomal Translocations:** The most common translocation is t(3;14)(q27;q32), which fuses *BCL6* to the *IGH* locus. Other partners include the *IGK* (2p12) and *IGL* (22q11) loci. These translocations place *BCL6* under the control of powerful immunoglobulin enhancers, leading to constitutive overexpression. Translocations can also occur with non-IG partners, such as *HIST1H4I* (6p22), *CIITA* (16p13), and *TFCR* (3q27), which can also drive overexpression. 2. **Somatic Hypermutation (SHM):** The 5' regulatory region of *BCL6* is a frequent target of aberrant SHM, a process normally confined to immunoglobulin genes. These mutations can disrupt the autoregulatory loop, leading to BCL6 overexpression. They can also create novel transcription factor binding sites or disrupt repressor binding sites. 3. **Gene Amplification:** In some cases, amplification of the 3q27 region leads to increased *BCL6* copy number and expression. 4. **Epigenetic Dysregulation:** Alterations in DNA methylation and histone modifications at the *BCL6* promoter can lead to aberrant expression. ### 4.2 Specific Pathogenic Mutations While *BCL6* is not a classic tumor suppressor, mutations that disrupt its negative regulation or alter its function are oncogenic. Key mutations include: - **Promoter Mutations:** These are the most common mutations. They are clustered in the first intron and the 5' UTR, within the autoregulatory binding sites. These mutations prevent BCL6 from binding to its own promoter, leading to loss of autoregulation and constitutive expression. - **Missense Mutations in the BTB Domain:** These mutations can disrupt the corepressor binding groove, either abrogating or enhancing corepressor recruitment. Some mutations, such as those at the dimer interface, can affect dimerization and DNA binding. - **Missense Mutations in the Zinc Finger Domain:** These mutations can alter DNA binding specificity or affinity. Some mutations may create a dominant-negative protein that interferes with the function of the wild-type protein. - **Frameshift and Nonsense Mutations:** These are less common but can lead to truncated proteins that lack critical functional domains. ### 4.3 Clinical Differentials and Disease Associations BCL6 dysregulation is a defining feature of several lymphomas: - **Diffuse Large B-Cell Lymphoma (DLBCL):** BCL6 is overexpressed in 30-40% of DLBCL cases. It is particularly associated with the activated B-cell (ABC) subtype, which has a poorer prognosis. BCL6 expression is an independent prognostic marker in some studies. - **Follicular Lymphoma (FL):** BCL6 translocations are present in 5-15% of FL cases. BCL6 expression is a hallmark of the GC B-cell phenotype of FL. - **Burkitt Lymphoma (BL):** BCL6 is expressed in nearly all BL cases, reflecting its GC B-cell origin. - **Hodgkin Lymphoma (HL):** BCL6 is expressed in a subset of Hodgkin and Reed-Sternberg (HRS) cells. - **Other Cancers:** BCL6 is also overexpressed in some solid tumors, including breast cancer, lung cancer, and glioblastoma, where it may contribute to cell proliferation and survival. ### 4.4 BCL6 in Non-Malignant Diseases Beyond cancer, BCL6 is implicated in: - **Autoimmune Diseases:** BCL6 is required for the development of T follicular helper (Tfh) cells, which are critical for autoantibody production in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). BCL6 expression is elevated in Tfh cells from patients with these diseases. - **Inflammatory Diseases:** BCL6 is involved in the regulation of macrophage and T-cell inflammatory responses. It can repress the expression of pro-inflammatory cytokines. - **Metabolic Diseases:** BCL6 regulates genes involved in lipid and glucose metabolism. It is expressed in the liver and adipose tissue, where it can influence insulin sensitivity and energy expenditure. --- ## 5. Host-Pathogen & Viral Interactions ### 5.1 Viral Oncoproteins and BCL6 Several viruses that are associated with B-cell lymphomas have evolved mechanisms to manipulate BCL6 expression or function. - **Epstein-Barr Virus (EBV):** EBV is a gamma-herpesvirus that infects B cells and is associated with several lymphomas, including Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorders. EBV-encoded proteins, such as **EBNA2** and **LMP1**, can modulate BCL6 expression. LMP1, a constitutively active CD40 mimic, activates NF-κB, which represses *BCL6* transcription. However, in some contexts, EBV can promote BCL6 expression to maintain the GC phenotype and prevent apoptosis of infected B cells. The EBV-encoded small RNAs (EBERs) may also influence BCL6 expression. - **Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8):** KSHV is associated with primary effusion lymphoma (PEL), a rare B-cell lymphoma. KSHV encodes a viral homolog of the cellular BCL6 corepressor, **vIRF3** (viral interferon regulatory factor 3). vIRF3 can interact with BCL6 and modulate its transcriptional activity, potentially contributing to the pathogenesis of PEL. - **Human Immunodeficiency Virus (HIV):** HIV infection is associated with an increased risk of B-cell lymphomas. HIV can cause chronic B-cell activation and dysregulation of the GC reaction, which may indirectly affect BCL6 expression. ### 5.2 Bacterial Effectors and Immune Evasion While direct interactions between bacterial effectors and BCL6 are less well-characterized, certain bacterial infections can influence the GC reaction and BCL6 expression. - ***Helicobacter pylori*:** Chronic *H. pylori* infection is a risk factor for gastric MALT lymphoma. The chronic inflammation and B-cell activation associated with this infection can lead to the formation of tertiary lymphoid structures with GCs, where BCL6 is expressed. However, the direct effect of *H. pylori* effectors on BCL6 is not well-defined. - ***Salmonella* and other intracellular pathogens:** These pathogens can modulate host immune responses, potentially affecting Tfh cell differentiation and BCL6 expression. ### 5.3 BCL6 in Immune Evasion BCL6 plays a role in immune evasion by promoting the survival of GC B cells, which are prone to DNA damage. By repressing *TP53* and other pro-apoptotic genes, BCL6 allows B cells to survive the genotoxic stress of SHM. This survival function can be co-opted by viruses and cancer cells to evade immune surveillance. In the context of viral infection, BCL6 may help maintain a reservoir of infected B cells by preventing their differentiation into antibody-secreting plasma cells. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors ### 6.1 BCL6 as a Therapeutic Target Given its central role in lymphomagenesis and its well-defined structure, BCL6 is an attractive therapeutic target. The goal of BCL6-targeted therapy is to inhibit its transcriptional repressor function, thereby reactivating the expression of pro-apoptotic and cell cycle checkpoint genes, leading to lymphoma cell death. ### 6.2 Small-Molecule Inhibitors of the BTB Domain The most advanced class of BCL6 inhibitors targets the corepressor binding groove on the BTB domain. By blocking the interaction between BCL6 and NCOR1/SMRT/BCOR, these inhibitors abrogate BCL6's repressive function. - **RI-BPI (Retinoid Inhibitor of BCL6 - Peptide Inhibitor):** This is a cell-penetrating peptide that mimics the BCL6-binding domain (BBD) of corepressors. It binds to the BTB domain groove with high affinity and disrupts BCL6-corepressor interactions. In preclinical studies, RI-BPI induced apoptosis in DLBCL cell lines and inhibited tumor growth in xenograft models. - **FX1:** A small-molecule inhibitor identified through a structure-based virtual screen. FX1 binds to the BTB domain groove and inhibits BCL6-mediated repression. It has shown efficacy in preclinical models of DLBCL. - **79-6:** Another small-molecule inhibitor that targets the BTB domain. It has been shown to reactivate BCL6 target genes and induce cell death in lymphoma cells. - **BI-3802 and BI-3812:** These are potent, selective small-molecule degraders (PROTACs) that bind to the BTB domain and recruit an E3 ubiquitin ligase, leading to the proteasomal degradation of BCL6. These compounds have shown profound anti-tumor activity in preclinical models. ### 6.3 Inhibitors of the DNA-Binding Domain Another strategy is to inhibit BCL6's ability to bind to DNA. Small molecules that bind to the zinc finger domain and block DNA interaction are being explored, though this approach is more challenging due to the highly charged nature of the protein-DNA interface. ### 6.4 Other Therapeutic Approaches - **HDAC Inhibitors:** Since BCL6 recruits HDACs to repress transcription, HDAC inhibitors (e.g., vorinostat, romidepsin) can partially reverse BCL6-mediated repression. These drugs are FDA-approved for certain T-cell lymphomas and are being tested in combination with other agents for DLBCL. - **EZH2 Inhibitors:** BCL6 recruits PRC2 (via BCOR) to promote H3K27me3. EZH2 inhibitors (e.g., tazemetostat) are FDA-approved for epithelioid sarcoma and follicular lymphoma and may be effective in BCL6-driven lymphomas. - **Immunotherapy:** Monoclonal antibodies targeting B-cell surface markers (e.g., rituximab targeting CD20) are standard of care for B-cell lymphomas. These can be combined with BCL6 inhibitors. - **Gene Therapy:** While not yet in clinical trials for BCL6, gene therapy approaches using CRISPR/Cas9 to disrupt the *BCL6* gene or its regulatory elements are being explored in preclinical models. ### 6.5 Pharmacogenomics The response to BCL6-targeted therapy may be influenced by genetic variations in *BCL6* itself or in genes encoding its corepressors and downstream targets. For example, mutations in the BTB domain that alter the corepressor binding groove may affect the efficacy of BTB-targeting inhibitors. Similarly, mutations in the zinc finger domain may affect DNA binding and the response to DNA-binding inhibitors. Pharmacogenomic studies are needed to identify biomarkers that can predict response to BCL6-targeted therapies. --- ## 7. Bioinformatic Resources & Database Accessions | **Database** | **Accession / ID** | **Description** | | :--- | :--- | :--- | | **NCBI Gene** | 604 | Gene ID for BCL6 | | **Ensembl** | ENSG00000113916 | Ensembl Gene ID | | **UniProt** | P41182 | Primary protein accession | | **RCSB PDB** | 1R28, 2EN2, 3BIM, 4CP3, 5N2C | Representative structures (BTB domain, zinc fingers, etc.) | | **OMIM** | 109565 | Online Mendelian Inheritance in Man entry | | **ClinVar** | (Various) | Clinical variants associated with BCL6 | | **COSMIC** | (Various) | Catalogue of Somatic Mutations in Cancer | | **STRING** | 604 (Homo sapiens) | Protein-protein interaction network | | **BioGRID** | 10866 | Biological General Repository for Interaction Datasets | | **Gene Ontology (GO)** | GO:0000978, GO:0003714, GO:0000122 | RNA polymerase II cis-regulatory region sequence-specific DNA binding, transcription corepressor activity, negative regulation of transcription by RNA polymerase II | | **KEGG** | hsa:604 | KEGG Gene entry | | **Reactome** | R-HSA-... | Reactome pathways involving BCL6 | --- ## Related Clinical & Scientific Guides * [PIK3CA (PI3K Alpha): Helical and Kinase Domain Hotspot Mutations and Isoform-Specific Inhibition](/knowledge/bioinformatics/genes/cancer-genomics/pik3ca-gene-structure-function-pathway) * [ENTPD5 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/entpd5-gene-structure-function-pathway) * [PDGFB Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/cancer-genomics/pdgfb-gene-structure-function-pathway) ## References 1. 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