BCL6
BCL6 (B-cell lymphoma 6 protein) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Lung cancer, Myeloproliferative neoplasms and 3 more.
Overview
Transcriptional repressor mainly required for germinal centre (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors.
CIViC holds 2 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.63 (direct and indirect evidence; datatypes literature 0.99, animal model 0.29, genetic association 0.00, somatic mutation 0.98). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · BCL6 (B-cell lymphoma 6 protein) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Lung cancer, Myeloproliferative neoplasms and 3 more.
- 1 · What it is
BCL6 (B-cell lymphoma 6 protein) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Lung cancer, Myeloproliferative neoplasms and 3 more.
- 2 · What goes wrong in cancer
Transcriptional repressor mainly required for germinal centre (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.
- 3 · How drugs use it
No product in this corpus aims at BCL6 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Sources: HGNC HGNC:1001 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P41182 (protein name, function text, keywords and locations (REST API)); CIViC gene BCL6 (2 evidence items, 0 assertions, 2 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000113916 (association with cancer (MONDO_0004992) 0.63; per-cancer scores at or above 0.5: colorectal cancer 0.52, diffuse large B-cell lymphoma 0.60, non-Hodgkin lymphoma 0.66, skin cancer 0.52, myeloproliferative neoplasm 0.53, lung cancer 0.53 (GraphQL API, CC0)); IntOGen BCL6 (driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Transcriptional repressor mainly required for germinal centre (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunoglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Location: Nucleus (UniProt). Locus 3q27.3 (HGNC).
- Non-Hodgkin lymphoma: Open Targets association 0.66 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM)
- Lung cancer: Open Targets association 0.53 with lung cancer (MONDO_0008903)
- Myeloproliferative neoplasms: Open Targets association 0.53 with myeloproliferative neoplasm (MONDO_0020076)
- Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
- Diffuse large B-cell lymphoma: Open Targets association 0.60 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 2 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"BCL6" OR ABSTRACT:"BCL6" OR TITLE:"BCL6 transcription repressor" OR ABSTRACT:"BCL6 transcription repressor" OR TITLE:"B-cell lymphoma 6 protein" OR ABSTRACT:"B-cell lymphoma 6 protein" OR TITLE:"ZBTB27" OR ABSTRACT:"ZBTB27" OR TITLE:"LAZ3" OR ABSTRACT:"LAZ3" OR TITLE:"BCL5" OR ABSTRACT:"BCL5") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about BCL6, not a curated reading list.
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