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…

GOFmechanismARLOEUF 0.736 OMIM phenotypes

Clinical Summary— BCL10

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Gene-Disease Validity (ClinGen)

immunodeficiency 37 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

20 unique Pathogenic / Likely Pathogenic· 53 VUS of 146 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.337

Z-score 2.09

OE 0.23 (0.09–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.39Z-score

OE missense 0.65 (0.54–0.78)

80 obs / 123.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.09–0.73)

0≤0.351.4

Missense OE?0.65 (0.54–0.78)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 2 / 8.6Missense obs/exp: 80 / 123.5Syn Z: -0.82

This gene — mechanism propensity

0.4883th %ile

GOF

0.81top 10%

LOF

0.3551th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20

VUS53

Likely Benign55

Benign6

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	3	0	0	20
Likely Pathogenic	0	0	0	0	0
VUS	3	48	2	0	53
Likely Benign	0	2	11	42	55
Benign	0	0	5	1	6
Total	20	53	18	43	134

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap BCL10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →