BCL3

protein-coding

BCL3 transcription coactivator, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes

Gene summary

This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional co-activator that activates through its association with NF-kappa B homodimers. The expression of this gene can be induced by NF-kappa B, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-kappa B. [provided by RefSeq, Jul 2008]

Previous symbols:

D19S37
BCL4

MANE transcript

NM_005178.5

Inheritance

—

ClinVar variants

U:67B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:44,747,705-44,760,044

External References & Databases

Ensembl (ENSG00000069399)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005178.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			61 clinvar		1 clinvar	62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	67	0	3	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005178.5	RefSeq	NP_005169.2	9	MANE Select
ENST00000164227.10	Ensembl	ENSP00000164227.5	9	MANE Select
ENST00000444487.1	Ensembl	ENSP00000393731.1	8	Standard
ENST00000987216.1	Ensembl	ENSP00000657033.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNF signaling pathway - Homo sapiens (human)
C-type lectin receptor signaling pathway - Homo sapiens (human)
Apoptosis-related network due to altered Notch3 in ovarian cancer
Photodynamic therapy-induced AP-1 survival signaling.
TNFalpha

Biological Process

obsolete protein import into nucleus, translocation
follicular dendritic cell differentiation
marginal zone B cell differentiation
humoral immune response mediated by circulating immunoglobulin
germinal center formation

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding
transcription factor binding
protein binding, bridging

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000164227
Coding exons: 9
Length: 12340
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	142	241	0.588	0.0000149	2808
Missense (PolyPhen)		20	66.222	0.30202		783
Synonymous	2.82	70	107	0.654	0.00000720	1040
Loss of Function	3.41	0	13.5	0.00	7.04e-7	165

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Contributes to the regulation of transcriptional activation of NF-kappa-B target genes. In the cytoplasm, inhibits the nuclear translocation of the NF-kappa-B p50 subunit. In the nucleus, acts as transcriptional activator that promotes transcription of NF-kappa-B target genes. Contributes to the regulation of cell proliferation (By similarity). {ECO:0000250, ECO:0000269|PubMed:8453667}.;
Disease: DISEASE: Note=A chromosomal aberration involving BCL3 may be a cause of B-cell chronic lymphocytic leukemia (B-CLL). Translocation t(14;19)(q32;q13.1) with immunoglobulin gene regions. {ECO:0000269|PubMed:2180580, ECO:0000269|PubMed:7896265}.;

Recessive Scores

pRec: 0.288

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium