BCL10

Chr 1AR

BCL10 immune signaling adaptor

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

NCBI Gene: 8915ENSG00000142867UniProt: O95999OMIM: 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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
37 unique Pathogenic / Likely Pathogenic· 55 VUS of 166 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 OE0.23 (0.09–0.73)
0≤0.351.4
Missense OE0.65 (0.54–0.78)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
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

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic3
VUS55
Likely Benign55
Benign6
34
Pathogenic
3
Likely Pathogenic
55
VUS
55
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
3
14
0
34
Likely Pathogenic
0
0
3
0
3
VUS
3
48
4
0
55
Likely Benign
0
2
11
42
55
Benign
0
0
5
1
6
Total20533743153

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

View 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients