BCL6

Chr 3

BCL6 transcription repressor

Also known as: BCL5, BCL6A, LAZ3, ZBTB27, ZNF51

The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.33
Clinical SummaryBCL6
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
56 VUS of 97 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — BCL6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.33LOEUF
pLI 0.960
Z-score 4.17
OE 0.14 (0.070.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.25Z-score
OE missense 0.70 (0.640.77)
312 obs / 445.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.14 (0.070.33)
00.351.4
Missense OE?0.70 (0.640.77)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 4 / 27.7Missense obs/exp: 312 / 445.3Syn Z: -0.22

This gene — mechanism propensity

DN
0.4190th %ile
GOF
0.2796th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.33

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

97 submitted variants in ClinVar

Classification Summary

VUS56
Likely Benign6
Benign4
56
VUS
6
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
56
0
0
56
Likely Benign
0
2
2
2
6
Benign
0
0
1
3
4
Total0583566

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

40 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap BCL6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

BCL6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Burkitt LymphomaDouble-Expressor LymphomaHigh Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements

Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene

RECRUITING
NCT07069699Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2026-10-13
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Diffuse Large B Cell Lymphoma

Mixed Molecular Clinical Index (MMCI) in Diffuse Large B-cell Lymphoma (DLBCL)

RECRUITING
NCT04300101Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSStarted 2020-05-14
Prospective cohortRetrospective cohort
Diffuse Large B Cell LymphomaHigh-grade B-cell LymphomaHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Exploring the Clinical Impact of MYC Aberrations and Their Relationship With Microenvironment in Diffuse Large B Cell Lymphoma and High-Grade B Cell Lymphoma

RECRUITING
NCT06588205Fondazione Italiana Linfomi - ETSStarted 2025-05-05
Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypeRefractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type

Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT02443077Phase PHASE3National Cancer Institute (NCI)Started 2016-10-12
Autologous Bone Marrow TransplantationAutologous Hematopoietic Stem Cell TransplantationCarmustine
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveAcute Biphenotypic LeukemiaAcute Lymphoblastic Leukemia

Personalized NK Cell Therapy in CBT

RECRUITING
NCT02727803Phase PHASE2M.D. Anderson Cancer CenterStarted 2016-05-19
Allogeneic Natural Killer Cell Line NK-92Anti-Thymocyte GlobulinBusulfan
Insulin ResistanceObesity & OverweightEnergy Metabolism

Effects of Ketone Bodies on Insulin Sensitivity

RECRUITING
NCT07359625Phase NAUniversity of AarhusStarted 2025-12-02
Growth Hormone, HumanOral ketone supplement (KetoAid®, KE4)Saline infusion (placebo)
High-grade B-cell LymphomaBurkitt LymphomaLymphoma, B-Cell

Sepantronium Bromide for the Treatment of High-grade B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT05263583Phase PHASE2Cothera Bioscience, IncStarted 2022-12-09
Sepantronium Bromide
Bone Marrow Failure DisordersVEXAS SyndromeHemoglobinurea, Paroxysmal

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

ENROLLING BY INVITATION
NCT07102849National Heart, Lung, and Blood Institute (NHLBI)Started 2025-09-09
Diffuse Large B-Cell LymphomaDiffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedDouble-Expressor Lymphoma

Testing the Addition of a New Anti-cancer Drug, Venetoclax, to Usual Chemotherapy for High Grade B-cell Lymphomas

ACTIVE NOT RECRUITING
NCT03984448Phase PHASE2, PHASE3National Cancer Institute (NCI)Started 2019-10-22
Biospecimen CollectionBone Marrow BiopsyComputed Tomography
B-cell Non-Hodgkin's Lymphoma

A Phase 1/2 Study of CT120 in Patient With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

NOT YET RECRUITING
NCT05091541Phase PHASE1, PHASE2Nanjing IASO Biotechnology Co., Ltd.Started 2021-10-20
Fully Human Anti-CD19/CD22 Dual Target Chimeric Antigen Receptor Autologous T Cell Injection
Recurrent Diffuse Large B-Cell LymphomaRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Fecal Microbiome Transplant to Remodel Intestinal Microbiota for Patients With Relapsed or Refractory Lymphoma With Exposure to High-Risk Antibiotics Who Are Receiving Chimeric Antigen Receptor T Cells

RECRUITING
NCT07042438Phase PHASE2City of Hope Medical CenterStarted 2026-02-11
Axicabtagene CiloleucelBiospecimen CollectionChemotherapy
Diffuse Large B-Cell Lymphoma Associated With Chronic InflammationEBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedHigh Grade B-Cell Lymphoma, Not Otherwise Specified

Zanubrutinib and CAR T-cell Therapy for the Treatment of Recurrent or Refractory Aggressive B-cell Non-Hodgkin's Lymphoma or Transformed Indolent B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT05202782Phase PHASE2Northwestern UniversityStarted 2022-03-21
Chimeric Antigen Receptor T-Cell TherapyQuality-of-Life AssessmentQuestionnaire Administration