BCL6
BCL6 transcription repressor, the group of Zinc fingers C2H2-type|BTB domain containing
Basic information
Region (hg38): 3:187721377-187745725
Previous symbols: [ "ZNF51" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
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 | |||||
| missense | 24 | 25 | ||||
| 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 | 24 | 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) | |||
| 3-187722593-C-A | not specified | Uncertain significance (Jun 29, 2023) | ||
| 3-187725070-G-T | not specified | Uncertain significance (Nov 12, 2021) | ||
| 3-187725085-G-A | Likely benign (Mar 01, 2024) | |||
| 3-187726810-G-T | not specified | Uncertain significance (Mar 06, 2023) | ||
| 3-187726889-GC-AT | not specified | not provided (Sep 19, 2013) | ||
| 3-187728423-C-T | not specified | not provided (Sep 19, 2013) | ||
| 3-187728483-G-T | not specified | Uncertain significance (Feb 07, 2023) | ||
| 3-187728525-G-A | not specified | not provided (Sep 19, 2013) | ||
| 3-187728528-G-A | not specified | Uncertain significance (Jan 12, 2024) | ||
| 3-187728536-G-A | not specified | not provided (Sep 19, 2013) | ||
| 3-187728547-A-G | Likely benign (Mar 01, 2024) | |||
| 3-187729072-G-A | not specified | Uncertain significance (Apr 25, 2023) | ||
| 3-187729103-G-T | not specified | Uncertain significance (Dec 08, 2023) | ||
| 3-187729138-G-A | not specified | Uncertain significance (May 15, 2023) | ||
| 3-187729156-G-C | not specified | Uncertain significance (Aug 16, 2021) | ||
| 3-187729164-C-T | not specified | Uncertain significance (Sep 12, 2023) | ||
| 3-187729179-G-A | not specified | Uncertain significance (Aug 13, 2021) | ||
| 3-187729188-C-T | not specified | Uncertain significance (Oct 20, 2021) | ||
| 3-187729200-C-T | Likely benign (Dec 19, 2018) | |||
| 3-187729201-G-A | not specified | Uncertain significance (Feb 23, 2023) | ||
| 3-187729239-T-C | not specified | not provided (Sep 19, 2013) | ||
| 3-187729296-G-T | not specified | Uncertain significance (Jun 28, 2023) | ||
| 3-187729432-G-A | not specified | Uncertain significance (Dec 15, 2022) | ||
| 3-187729443-G-A | not specified | not provided (Sep 19, 2013) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BCL6 | protein_coding | protein_coding | ENST00000406870 | 8 | 24351 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.960 | 0.0396 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.25 | 312 | 445 | 0.701 | 0.0000273 | 4666 |
| Missense in Polyphen | 51 | 149.34 | 0.3415 | 1594 | ||
| Synonymous | -0.219 | 171 | 167 | 1.02 | 0.00000966 | 1392 |
| Loss of Function | 4.17 | 4 | 27.7 | 0.144 | 0.00000167 | 305 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000905 | 0.0000905 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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