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)

Definitive · immunodeficiency 37 · AR · ClinGen 2022

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: Error: Service overloaded

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in BCL10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

218 rare PASS variants

Rare truncating (LoF)

1 in 5,300

22 rare PASS variants

Rare synonymous (reference)

1 in 750

118 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCL10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 450	1 in 6,300
South Asian	~43k	1 in 240	1 in 3,800
Remaining (unassigned)	~30k	1 in 300	≈ 1 in 10,000
European (Finnish)	~27k	1 in 490	≈ 1 in 8,800
Admixed American	~22k	1 in 210	1 in 2,900
African / African American	~21k	1 in 630	1 in 2,500
East Asian	~20k	1 in 430	none seen
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	1 in 260	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓