BCL10

BCL10 immune signaling adaptor, the group of CBM complex|Caspase recruitment domain containing

Basic information

Region (hg38): 1:85265776-85276632

Links

ENSG00000142867 ∙ NCBI:8915 ∙ OMIM:603517 ∙ HGNC:989 ∙ Uniprot:O95999 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 37 (Strong), mode of inheritance: AR
• immunodeficiency 37 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 37	AR	Allergy/Immunology/Infectious	Individuals have been described as susceptible to severe infections, and awareness may allow preventive measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious	25365219

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCL10 gene.

• Immunodeficiency 37 (3 variants)
• Male germ cell tumor, somatic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCL10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				31	1	32
missense			40		2	42
nonsense	2		1			3
start loss			1			1
frameshift	1		1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	5	2	8
non coding				4	2	6
Total	3	0	44	35	5

Variants in BCL10

This is a list of pathogenic ClinVar variants found in the BCL10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-85267630-T-C		Immunodeficiency 37	Likely benign (Dec 22, 2023)
1-85267634-C-T		Immunodeficiency 37	Uncertain significance (Oct 29, 2021)
1-85267635-G-A		Immunodeficiency 37 • Germ cell tumor of testis;Mucosa-associated lymphoma;Mesothelioma, malignant;Immunodeficiency 37;Lymphoma, non-Hodgkin, familial	Uncertain significance (Mar 18, 2022)
1-85267642-A-G		Immunodeficiency 37	Likely benign (Oct 13, 2023)
1-85267644-T-A		Immunodeficiency 37	Uncertain significance (Jun 03, 2022)
1-85267647-G-A		Immunodeficiency 37	Uncertain significance (Aug 23, 2022)
1-85267680-T-C		Immunodeficiency 37	Uncertain significance (Jan 23, 2020)
1-85267689-T-C		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
1-85267691-C-T		not specified • Immunodeficiency 37	Benign (Feb 01, 2024)
1-85267691-CCTT-C		Follicular lymphoma	Pathogenic (Jan 08, 1999)
1-85267705-C-G		Immunodeficiency 37	Uncertain significance (May 29, 2022)
1-85267708-T-C		Immunodeficiency 37	Likely benign (Sep 28, 2022)
1-85267732-C-T		Immunodeficiency 37	Likely benign (Feb 06, 2022)
1-85267741-C-T		Immunodeficiency 37	Likely benign (Jan 16, 2019)
1-85267751-G-A		Immunodeficiency 37	Uncertain significance (May 19, 2022)
1-85267761-T-C		Immunodeficiency 37	Uncertain significance (Jul 06, 2022)
1-85267777-A-G		Immunodeficiency 37	Likely benign (Jun 07, 2021)
1-85267787-CTGCCTACTTCTAGAACA-C		Follicular lymphoma	Pathogenic (Jan 08, 1999)
1-85267799-A-C		Immunodeficiency 37	Uncertain significance (Aug 27, 2021)
1-85267800-G-A		Immunodeficiency 37	Likely benign (Nov 17, 2018)
1-85267800-G-C		Immunodeficiency 37	Uncertain significance (Dec 04, 2019)
1-85267800-G-T		Immunodeficiency 37 • Inborn genetic diseases	Uncertain significance (Apr 25, 2024)
1-85267824-T-G		Immunodeficiency 37	Uncertain significance (Jan 04, 2022)
1-85267829-G-GA		Mucosa-associated lymphoma • Mesothelioma • Male germ cell tumor, somatic	Pathogenic (Jul 01, 1999)
1-85267840-C-T		Immunodeficiency 37 • BCL10-related disorder	Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCL10	protein_coding	protein_coding	ENST00000370580	3	10843

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.337	0.650	125736	0	3	125739	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	80	124	0.648	0.00000637	1495
Missense in Polyphen		14	30.934	0.45258		375
Synonymous	-0.818	52	45.0	1.16	0.00000216	473
Loss of Function	2.09	2	8.61	0.232	5.17e-7	109

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in adaptive immune response (PubMed:25365219). Promotes apoptosis, pro-caspase-9 maturation and activation of NF- kappa-B via NIK and IKK. May be an adapter protein between upstream TNFR1-TRADD-RIP complex and the downstream NIK-IKK-IKAP complex. Is a substrate for MALT1 (PubMed:18264101). {ECO:0000269|PubMed:18264101, ECO:0000269|PubMed:25365219}.
• Disease: DISEASE: Note=A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.; DISEASE: Immunodeficiency 37 (IMD37) [MIM:616098]: A form of primary combined immunodeficiency, a group of disorders characterized by severe recurrent infections, with normal numbers or an absence of T and B lymphocytes, and impaired cellular and humoral immunity. IMD37 is characterized by hypogammaglobulinemia without lymphopenia, but with profoundly reduced memory B cells and memory T cells, and increased numbers of circulating naive lymphocytes. Inheritance is autosomal recessive. {ECO:0000269|PubMed:25365219}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lymphoma, mucosa-associated lymphoid type (MALTOMA) [MIM:137245]: A subtype of non-Hodgkin lymphoma, originating in mucosa-associated lymphoid tissue. MALT lymphomas occur most commonly in the gastro-intestinal tract but have been described in a variety of extranodal sites including the ocular adnexa, salivary gland, thyroid, lung, thymus, and breast. Histologically, they are characterized by an infiltrate of small to medium-sized lymphocytes with abundant cytoplasm and irregularly shaped nuclei. Scattered transformed blasts (large cells) also are present. Non- malignant reactive follicles are observed frequently. A pivotal feature is the presence of lymphoepithelial lesions, with invasion and partial destruction of mucosal glands and crypts by aggregates of tumor cells. {ECO:0000269|PubMed:9989495}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);B Cell Receptor Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;T-Cell antigen Receptor (TCR) Signaling Pathway;B cell receptor signaling;Downstream TCR signaling;TCR signaling;Post-translational protein modification;Activation of NF-kappaB in B cells;Metabolism of proteins;Signaling by the B Cell Receptor (BCR);CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);BCR;BCR signaling pathway;Protein ubiquitination;FCERI mediated NF-kB activation;Canonical NF-kappaB pathway;TCR signaling in naïve CD8+ T cells;E3 ubiquitin ligases ubiquitinate target proteins;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.266

Intolerance Scores

• loftool: 0.289
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.08

Haploinsufficiency Scores

• pHI: 0.759
• hipred: N
• hipred_score: 0.499
• ghis: 0.480

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bcl10
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: B cell apoptotic process;neural tube closure;stimulatory C-type lectin receptor signaling pathway;toll-like receptor signaling pathway;response to molecule of bacterial origin;adaptive immune response;negative regulation of mature B cell apoptotic process;cellular defense response;I-kappaB kinase/NF-kappaB signaling;cell death;response to fungus;immunoglobulin mediated immune response;protein ubiquitination;positive regulation of protein ubiquitination;lipopolysaccharide-mediated signaling pathway;response to food;positive regulation of mast cell cytokine production;positive regulation of kinase activity;Fc-epsilon receptor signaling pathway;lymphotoxin A biosynthetic process;interleukin-6 biosynthetic process;positive regulation of phosphorylation;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;innate immune response;positive regulation of interleukin-8 biosynthetic process;positive regulation of transcription, DNA-templated;T cell receptor signaling pathway;regulation of T cell receptor signaling pathway;positive regulation of T cell activation;positive regulation of NF-kappaB transcription factor activity;protein complex oligomerization;protein homooligomerization;protein heterooligomerization;T cell apoptotic process;cellular response to mechanical stimulus;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: immunological synapse;nucleus;cytoplasm;lysosome;cytosol;cytoplasmic microtubule;CBM complex;protein-containing complex;membrane raft;perinuclear region of cytoplasm
• Molecular function: protease binding;transcription coactivator activity;protein binding;protein C-terminus binding;transcription factor binding;kinase activator activity;enzyme binding;kinase binding;protein kinase binding;ubiquitin protein ligase binding;identical protein binding;protein kinase B binding;protein self-association;CARD domain binding;NF-kappaB binding