BCL10 (B-cell CLL/lymphoma 10)
2009-01-01 Pei Lin AffiliationDepartment of Hematopathology, University of Texas-MD Anderson Cancer Center Houston, Texas, 77030 USA
Identity
HGNC
LOCATION
1p22.3
LOCUSID
ALIAS
CARMEN,CIPER,CLAP,IMD37,c-E10,mE10
FUSION GENES
DNA/RNA
Description
12,308 bases, 4 exons, Transcription: 4.2 kb.
Transcription
Transcription produces 4 alternatively spliced variants and 1 unspliced form with 2,974 bps or 2,819 bps.
Proteins
Description
233 amino acids with a molecular weight of 26252 Da.
Expression
BCL10 is expressed in all normal and malignant tissues. In the lymphoid tissue, it is highly expressed in the germinal center but low in the mantle zone, and intermediate in the marginal zone. BCL10 is likely to play a role in the normal development of the germinal center.
Localisation
BCL10 resides in the cytoplasm or perinuclear region of normal cells.
Function
BCL10 functions normally as a proapoptotic protein through caspase recruitment domain (CARD) at the animo terminal and activation of NF-kappaB pathway. This activity requires oligomerization via the CARD domain and interaction between BCL10 and other CARD domain containing proteins including CARD9, CARD10, CARD11 and CARD14.
Homology
Equine herpesvirus-2 E10 gene.
Implicated in
Entity name
1p rearrangement/Non-Hodgkin lymphoma
Disease
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).
Phenotype stem cell origin: Marginal zone B-cells.
Epidemiology: Commonly seen in MALT lymphoma involving stomach (approximately 4%) and lung (approximately 9%). Uncommon in MALT lymphoma involving other sites.
Evolution: MALT lymphoma may evolve to diffuse large B-cell lymphoma.
Prognosis
Generally indolent.
Cytogenetics
In t(1;14)(p22;q32). The gene on 14q32 is IgH. The breakpoint on 1p22 involves a recurrent breakpoint upstream of the promoter of BCL10.
Hybrid gene
BCL10-IgH.
The translocation t(1;14)(p22;q32) is associated with frameshift mutation of BCL10 and truncation of BCL10 protein distal to CARD. The mutant type of BCL10 enhances cell survival and proliferation through activation of NF-kappaB pathway. MALT lymphomas without BCL10 rearrangement may also carry BCL10 mutation however.
The translocation t(1;14)(p22;q32) is associated with frameshift mutation of BCL10 and truncation of BCL10 protein distal to CARD. The mutant type of BCL10 enhances cell survival and proliferation through activation of NF-kappaB pathway. MALT lymphomas without BCL10 rearrangement may also carry BCL10 mutation however.
MALT lymphoma expressing BCL10 (courtesy of Dr. Du M-Q).
Fusion protein
MALT lymphomas with t(1;14)(p22;q32) demonstrate strong nuclear BCL10 staining regardless of BCL10 mutation status. MALT lymphoma without t(1;14)(p22;q32) may also show strong nuclear staining.So a strong nuclear BCL10 staining is not always a presumptive evidence of t(1;14)(p22;q32). This pattern is different from the weak cytoplasmic expression observed in normal germinal center B-cells.
Oncogenesis
Loss of CARD domain through translocation and mutations lead to loss of proapoptotic activity. In addition, MALT1 and BCL10 may synergize in the activation of NF-kappaB leading to enhanced cell survival and downstream activation of anti-apoptotic/proliferative signals.
Entity name
Various Cancers
Disease
BCL10 mutations have also been described in follicular lymphoma, Sezary syndrome, malignant mesothelioma, germ cell tumor, and colon cancer.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18040143 | 2007 | MALT lymphoma : recent advances in aetiology and molecular genetics. | Du MQ et al |
| 10845924 | 2000 | BCL10 gene mutation in lymphoma. | Du MQ et al |
| 9989495 | 1999 | Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. | Willis TG et al |
| 10319863 | 1999 | Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). | Zhang Q et al |
Other Information
Locus ID:
NCBI: 8915
MIM: 603517
HGNC: 989
Ensembl: ENSG00000142867
Variants:
dbSNP: 8915
ClinVar: 8915
TCGA: ENSG00000142867
COSMIC: BCL10
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000142867 | ENST00000620248 | A0A087WWW9 |
| ENSG00000142867 | ENST00000648566 | O95999 |
| ENSG00000142867 | ENST00000649060 | A0A3B3ISX2 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34928543 | 2023 | BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma. | 1 |
| 36537036 | 2023 | A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification. | 1 |
| 37991197 | 2023 | Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1? | 1 |
| 34928543 | 2023 | BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma. | 1 |
| 36537036 | 2023 | A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification. | 1 |
| 37991197 | 2023 | Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1? | 1 |
| 35658124 | 2022 | BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL. | 4 |
| 35727133 | 2022 | A nucleation barrier spring-loads the CBM signalosome for binary activation. | 4 |
| 35750252 | 2022 | BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency. | 4 |
| 35658124 | 2022 | BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL. | 4 |
| 35727133 | 2022 | A nucleation barrier spring-loads the CBM signalosome for binary activation. | 4 |
| 35750252 | 2022 | BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency. | 4 |
| 33640899 | 2021 | TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO. | 13 |
| 33640899 | 2021 | TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO. | 13 |
| 32008135 | 2020 | Human BCL10 Deficiency due to Homozygosity for a Rare Allele. | 7 |
Citation
Pei Lin
BCL10 (B-cell CLL/lymphoma 10)
Atlas Genet Cytogenet Oncol Haematol. 2009-01-01
Online version: http://atlasgeneticsoncology.org/gene/222/bcl10
