BCL10 (B-cell CLL/lymphoma 10)

2009-01-01   Pei Lin  

Department of Hematopathology, University of Texas-MD Anderson Cancer Center Houston, Texas, 77030 USA

Identity

HGNC
BCL10
LOCATION
1p22.3
LOCUSID
8915
ALIAS
CARMEN,CIPER,CLAP,IMD37,c-E10,mE10
FUSION GENES
Show Gene Fusions

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.
    Atlas Image
    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 IDLast YearTitleAuthors
    180401432007MALT lymphoma : recent advances in aetiology and molecular genetics.Du MQ et al
    108459242000BCL10 gene mutation in lymphoma.Du MQ et al
    99894951999Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.Willis TG et al
    103198631999Inactivating 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 IDTranscript IDUniprot
    ENSG00000142867ENST00000620248A0A087WWW9
    ENSG00000142867ENST00000648566O95999
    ENSG00000142867ENST00000649060A0A3B3ISX2

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    T cell receptor signaling pathwayKEGGko04660
    B cell receptor signaling pathwayKEGGko04662
    T cell receptor signaling pathwayKEGGhsa04660
    B cell receptor signaling pathwayKEGGhsa04662
    TuberculosisKEGGko05152
    TuberculosisKEGGhsa05152
    NF-kappa B signaling pathwayKEGGhsa04064
    NF-kappa B signaling pathwayKEGGko04064
    Metabolism of proteinsREACTOMER-HSA-392499
    Post-translational protein modificationREACTOMER-HSA-597592
    Immune SystemREACTOMER-HSA-168256
    Adaptive Immune SystemREACTOMER-HSA-1280218
    TCR signalingREACTOMER-HSA-202403
    Downstream TCR signalingREACTOMER-HSA-202424
    Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
    Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
    Activation of NF-kappaB in B cellsREACTOMER-HSA-1169091
    Innate Immune SystemREACTOMER-HSA-168249
    Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
    FCERI mediated NF-kB activationREACTOMER-HSA-2871837
    C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
    CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
    Protein ubiquitinationREACTOMER-HSA-8852135
    E3 ubiquitin ligases ubiquitinate target proteinsREACTOMER-HSA-8866654

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    349285432023BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma.1
    365370362023A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification.1
    379911972023Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?1
    349285432023BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma.1
    365370362023A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification.1
    379911972023Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?1
    356581242022BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL.4
    357271332022A nucleation barrier spring-loads the CBM signalosome for binary activation.4
    357502522022BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency.4
    356581242022BCL10 Mutations Define Distinct Dependencies Guiding Precision Therapy for DLBCL.4
    357271332022A nucleation barrier spring-loads the CBM signalosome for binary activation.4
    357502522022BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency.4
    336408992021TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO.13
    336408992021TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO.13
    320081352020Human 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-(b-cell-cll-lymphoma-10)