BCL10

Chr 1AR

BCL10 immune signaling adaptor

Also known as: CARMEN, CIPER, CLAP, IMD37, c-E10, mE10

NCBI Gene: 8915 ENSG00000142867 UniProt: O95999 OMIM: 603517

The BCL10 protein bridges CARD domain-containing proteins to activate NF-kappaB and MAP kinase p38 pathways in adaptive and innate immune signaling, playing a key role in antifungal immunity and T-cell/B-cell receptor responses. Autosomal recessive mutations cause immunodeficiency 37, presenting with increased susceptibility to infections due to impaired immune signaling. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.73), consistent with recessive inheritance where one functional copy provides some protection.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. This protein is found to form a complex with MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and this protein are thought to synergize in the activation of NF-kappaB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Immunodeficiency 37MIM #616098

{Lymphoma, follicular, somatic}MIM #605027

{Male germ cell tumor, somatic}MIM #273300

{Mesothelioma, somatic}MIM #156240

{Sezary syndrome, somatic}

Lymphoma, MALT, somaticMIM #137245

UniProtLymphoma, mucosa-associated lymphoid type

Clinical highlights

Gene-disease validity (ClinGen)

immunodeficiency 37 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.73

LOEUF

GOF

Mechanism· predicted