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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BCL6
BCL6 transcription repressor
Chromosome 3 · 3q27.3
NCBI Gene: 604Ensembl: ENSG00000113916.18HGNC: HGNC:1001UniProt: B5B0A5
434PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneOncogeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of transcription by RNA polymerase IIreplication forktranscription corepressor bindingDNA-binding transcription repressor activity, RNA polymerase II-specificdiffuse large B-cell lymphomaneurodegenerative diseaselymphoid neoplasmlymphoma
✦AI Summary

BCL6 is a transcriptional repressor essential for germinal center (GC) formation and antibody affinity maturation 12. As the lineage-defining transcription factor for T follicular helper (Tfh) cells, BCL6 promotes Tfh differentiation while inhibiting Th1, Th2, and Th17 cell development 12. BCL6 functions by binding to DNA sequences and recruiting corepressors and histone deacetylases to silence target genes involved in differentiation, apoptosis, and cell cycle control, allowing GC B-cells to tolerate DNA damage from somatic hypermutation and class switch recombination 3. In GC B-cells, BCL6 represses anti-proliferative genes while indirectly promoting pro-GC reactions through microRNA suppression 3. BCL6 dysregulation is clinically significant in hematologic malignancies. BCL6 rearrangements occur frequently in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), making BCL6 alterations important diagnostic markers 453. In acute myeloid leukemia (AML), elevated BCL6 maintains leukemia-initiating cell capacity and chemotherapy resistance; BCL6 inhibition reduces AML repopulating cell function without suppressing normal hematopoietic stem cells 6. Additionally, dysregulated BCL6 expression contributes to systemic lupus erythematosus through enhanced Tfh responses 7. BCL6 inhibitors represent a promising therapeutic strategy across multiple malignancies and autoimmune conditions.

Sources cited
1
BCL6 is the lineage-defining transcription factor for Tfh cell differentiation and is essential for germinal center formation and B cell antibody affinity maturation
PMID: 31117010
2
BCL6 is critical for Tfh cell differentiation, germinal center formation, and development of high-affinity antibodies and memory B cells
PMID: 25367570
3
BCL6 is a transcriptional repressor regulating GC formation, GC B cells, Tfh cells, and immune memory; also has oncogenic roles in DLBCL and FL with roles in therapy resistance
PMID: 39456751
4
BCL6 rearrangements are clinically important diagnostic features in high-grade B-cell lymphoma classification
PMID: 39689165
5
BCL6 rearrangements are frequent in DLBCL and can be detected by next-generation sequencing for clinical diagnosis
PMID: 38937822
6
BCL6 maintains survival and self-renewal of primary AML cells and leukemia-initiating capacity; BCL6 inhibition sensitizes AML to chemotherapy without affecting normal hematopoietic stem cells
PMID: 32911532
7
Elevated BCL6 expression drives hyper Tfh cell responses in SLE through the ICOS-CBL ubiquitination axis; BCL6 blockade can prevent SLE development
PMID: 38761804
Disease Associationsⓘ20
diffuse large B-cell lymphomaOpen Targets
0.52Moderate
neurodegenerative diseaseOpen Targets
0.48Moderate
lymphoid neoplasmOpen Targets
0.42Moderate
lymphomaOpen Targets
0.40Weak
multiple myelomaOpen Targets
0.38Weak
lung carcinomaOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
hemangioblastomaOpen Targets
0.37Weak
myeloproliferative neoplasm, unclassifiableOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
chronic myelogenous leukemiaOpen Targets
0.30Weak
chronic lymphocytic leukemiaOpen Targets
0.30Weak
gliomaOpen Targets
0.30Weak
hepatocellular carcinomaOpen Targets
0.30Weak
head and neck squamous cell carcinomaOpen Targets
0.30Weak
urinary bladder carcinomaOpen Targets
0.29Weak
gastric carcinomaOpen Targets
0.29Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOXO1Protein interaction100%MTA3Protein interaction100%BCORProtein interaction100%CD5Protein interaction100%NCOR1Protein interaction100%HDAC1Protein interaction99%
Tissue Expression6 tissues
Lung
100%
Ovary
38%
Liver
36%
Bone Marrow
23%
Brain
19%
Heart
17%
Gene Interaction Network
Click a node to explore
BCL6FOXO1MTA3BCORCD5NCOR1HDAC1
PROTEIN STRUCTURE
Preparing viewer…
PDB7LWE · 1.17 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.22Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.12 [0.07–0.22]
RankingsWhere BCL6 stands among ~20K protein-coding genes
  • #642of 20,598
    Most Researched434 · top 5%
  • #567of 17,882
    Most Constrained (LOEUF)0.22 · top 5%
Genes detectedBCL6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
T Follicular Helper Cell Biology: A Decade of Discovery and Diseases.
PMID: 31117010
Immunity · 2019
1.00
2
How I diagnose high-grade B-cell lymphoma.
PMID: 39689165
Am J Clin Pathol · 2025
0.90
3
T follicular helper cell differentiation, function, and roles in disease.
PMID: 25367570
Immunity · 2014
0.80
4
Double-Hit Large B Cell Lymphoma.
PMID: 28952038
Curr Oncol Rep · 2017
0.76
5
Deficiency of CBL and CBLB ubiquitin ligases leads to hyper T follicular helper cell responses and lupus by reducing BCL6 degradation.
PMID: 38761804
Immunity · 2024
0.70