BCL10

Chr 1AR

BCL10 immune signaling adaptor

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

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Immunodeficiency 37MIM #616098
AR
{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
0
Active trials
28
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.73
LOEUF
GOF
Mechanism· predicted
Clinical SummaryBCL10
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Gene-Disease Validity (ClinGen)
immunodeficiency 37 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.337
Z-score 2.09
OE 0.23 (0.090.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.39Z-score
OE missense 0.65 (0.540.78)
80 obs / 123.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.090.73)
00.351.4
Missense OE0.65 (0.540.78)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 2 / 8.6Missense obs/exp: 80 / 123.5Syn Z: -0.82
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BCL10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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