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GeneBe

BCL6

BCL6 transcription repressor, the group of Zinc fingers C2H2-type|BTB domain containing

Basic information

Region (hg38): 3:187721376-187745725

Previous symbols: [ "ZNF51" ]

Links

ENSG00000113916NCBI:604OMIM:109565HGNC:1001Uniprot:P41182AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCL6 gene.

  • Inborn genetic diseases (22 variants)
  • not specified (9 variants)
  • not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCL6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
3
clinvar
3
missense
22
clinvar
1
clinvar
23
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
2
1
3
non coding
0
Total 0 0 22 1 3

Variants in BCL6

This is a list of pathogenic ClinVar variants found in the BCL6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
3-187722497-T-C Benign (Dec 19, 2018)729093
3-187722593-C-A Inborn genetic diseases Uncertain significance (Jun 29, 2023)2607821
3-187725070-G-T Inborn genetic diseases Uncertain significance (Nov 12, 2021)2260739
3-187725085-G-A Likely benign (Dec 31, 2019)734312
3-187726810-G-T Inborn genetic diseases Uncertain significance (Mar 06, 2023)2458095
3-187726889-GC-AT not specified not provided (Sep 19, 2013)133668
3-187728423-C-T not specified not provided (Sep 19, 2013)133676
3-187728483-G-T Inborn genetic diseases Uncertain significance (Feb 07, 2023)2481684
3-187728525-G-A not specified not provided (Sep 19, 2013)133675
3-187728536-G-A not specified not provided (Sep 19, 2013)133674
3-187728547-A-G Likely benign (Dec 31, 2019)781975
3-187729072-G-A Inborn genetic diseases Uncertain significance (Apr 25, 2023)2540535
3-187729138-G-A Inborn genetic diseases Uncertain significance (May 15, 2023)2521673
3-187729156-G-C Inborn genetic diseases Uncertain significance (Aug 16, 2021)2245665
3-187729164-C-T Inborn genetic diseases Uncertain significance (Sep 12, 2023)2596525
3-187729179-G-A Inborn genetic diseases Uncertain significance (Aug 13, 2021)2228659
3-187729188-C-T Inborn genetic diseases Uncertain significance (Oct 20, 2021)2355053
3-187729200-C-T Likely benign (Dec 19, 2018)729094
3-187729201-G-A Inborn genetic diseases Uncertain significance (Feb 23, 2023)2461434
3-187729239-T-C not specified not provided (Sep 19, 2013)133670
3-187729296-G-T Inborn genetic diseases Uncertain significance (Jun 28, 2023)2606843
3-187729432-G-A Inborn genetic diseases Uncertain significance (Dec 15, 2022)2335230
3-187729443-G-A not specified not provided (Sep 19, 2013)133672
3-187729500-T-C not specified not provided (Sep 19, 2013)133671
3-187729671-G-A Inborn genetic diseases Uncertain significance (Feb 03, 2022)2375099

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BCL6protein_codingprotein_codingENST00000406870 824351
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9600.0396125744041257480.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.253124450.7010.00002734666
Missense in Polyphen51149.340.34151594
Synonymous-0.2191711671.020.000009661392
Loss of Function4.17427.70.1440.00000167305

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00009050.0000905
Ashkenazi Jewish0.00009920.0000992
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Transcriptional repressor mainly required for germinal center (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 immunglobulin 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. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53- dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH- dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation. {ECO:0000269|PubMed:10981963, ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:12414651, ECO:0000269|PubMed:12504096, ECO:0000269|PubMed:15454082, ECO:0000269|PubMed:15577913, ECO:0000269|PubMed:16142238, ECO:0000269|PubMed:17828269, ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:18280243, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23166356, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:9649500}.;
Disease
DISEASE: Note=Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain. Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region. Translocation t(3;6)(q27;p21) with Histone H4. Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1.; DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.; DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.;
Pathway
FoxO signaling pathway - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;B Cell Receptor Signaling Pathway;Vitamin D Receptor Pathway;MECP2 and Associated Rett Syndrome;TP53 Regulates Transcription of Cell Death Genes;Interleukin-4 and 13 signaling;DNA Damage Response (only ATM dependent);Gene expression (Transcription);Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;BCR;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;Signaling events mediated by HDAC Class II;Transcriptional Regulation by TP53;Direct p53 effectors;FoxO family signaling;IL4-mediated signaling events (Consensus)

Recessive Scores

pRec
0.517

Intolerance Scores

loftool
0.155
rvis_EVS
-0.46
rvis_percentile_EVS
23.57

Haploinsufficiency Scores

pHI
0.344
hipred
Y
hipred_score
0.783
ghis
0.497

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.976

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Bcl6
Phenotype
muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
bcl6aa
Affected structure
optic fissure
Phenotype tag
abnormal
Phenotype quality
open

Gene ontology

Biological process
obsolete protein import into nucleus, translocation;negative regulation of transcription by RNA polymerase II;cell morphogenesis;negative regulation of cell-matrix adhesion;germinal center formation;regulation of germinal center formation;negative regulation of B cell apoptotic process;inflammatory response;cellular response to DNA damage stimulus;Rho protein signal transduction;spermatogenesis;negative regulation of cell population proliferation;cytokine-mediated signaling pathway;actin cytoskeleton organization;B cell differentiation;negative regulation of cell growth;positive regulation of B cell proliferation;positive regulation of histone deacetylation;negative regulation of mast cell cytokine production;negative regulation of Rho protein signal transduction;type 2 immune response;regulation of cell population proliferation;regulation of apoptotic process;positive regulation of apoptotic process;regulation of GTPase activity;regulation of memory T cell differentiation;positive regulation of regulatory T cell differentiation;negative regulation of T-helper 2 cell differentiation;positive regulation of neuron differentiation;negative regulation of Notch signaling pathway;negative regulation of transcription, DNA-templated;negative regulation of isotype switching to IgE isotypes;erythrocyte development;regulation of inflammatory response;regulation of immune response;positive regulation of cellular component movement;negative regulation of mitotic cell cycle DNA replication;negative regulation of cellular senescence
Cellular component
nucleus;nucleoplasm;replication fork;Golgi apparatus
Molecular function
RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;intronic transcription regulatory region sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;chromatin DNA binding;identical protein binding;sequence-specific DNA binding;metal ion binding