BCL10

Summary

BCL10 (BCL10 immune signaling adaptor, HGNC:989) is a protein-coding gene on chromosome 1p22.3, encoding B-cell lymphoma/leukemia 10 (O95999). Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

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.

Source: NCBI Gene 8915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 37 (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 145 total — 20 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 38
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_003921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:989
Approved symbol	BCL10
Name	BCL10 immune signaling adaptor
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	CARMEN, CIPER, mE10, c-E10, CLAP
Ensembl gene	ENSG00000142867
Ensembl biotype	protein_coding
OMIM	603517
Entrez	8915

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000620248, ENST00000648566, ENST00000649060, ENST00000649434, ENST00000650582, ENST00000913809

RefSeq mRNA: 2 — MANE Select: NM_003921 NM_001320715, NM_003921

CCDS: CCDS704, CCDS90994

Canonical transcript exons

ENST00000648566 — 3 exons

Exon	Start	End
ENSE00000956833	85270618	85270906
ENSE00001427973	85265776	85267982
ENSE00003838709	85276296	85276632

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0149 / max 460.4234, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13027	28.4322	1811
13024	4.4665	1507
13026	3.7562	1549
13025	0.3600	168

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	97.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.97	gold quality
squamous epithelium	UBERON:0006914	96.86	gold quality
oocyte	CL:0000023	96.75	gold quality
colonic mucosa	UBERON:0000317	96.63	gold quality
gingival epithelium	UBERON:0001949	96.50	gold quality
secondary oocyte	CL:0000655	96.43	gold quality
epithelium of nasopharynx	UBERON:0001951	96.31	gold quality
epithelium of esophagus	UBERON:0001976	95.63	gold quality
cervix squamous epithelium	UBERON:0006922	95.27	gold quality
palpebral conjunctiva	UBERON:0001812	94.81	gold quality
germinal epithelium of ovary	UBERON:0001304	94.71	gold quality
amniotic fluid	UBERON:0000173	94.69	gold quality
gingiva	UBERON:0001828	94.34	gold quality
tibia	UBERON:0000979	93.39	gold quality
jejunal mucosa	UBERON:0000399	93.22	gold quality
oral cavity	UBERON:0000167	92.85	gold quality
tongue squamous epithelium	UBERON:0006919	92.69	gold quality
visceral pleura	UBERON:0002401	92.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.37	gold quality
upper leg skin	UBERON:0004262	92.18	gold quality
endothelial cell	CL:0000115	91.96	gold quality
rectum	UBERON:0001052	91.87	gold quality
pancreatic ductal cell	CL:0002079	91.29	gold quality
pleura	UBERON:0000977	91.25	gold quality
parietal pleura	UBERON:0002400	91.14	gold quality
calcaneal tendon	UBERON:0003701	91.13	gold quality
hair follicle	UBERON:0002073	90.83	gold quality
cervix epithelium	UBERON:0004801	90.82	gold quality
nephron tubule	UBERON:0001231	90.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	10.76
E-ENAD-27	yes	6.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, RELA, RELB, STAT5A

miRNA regulators (miRDB)

91 targeting BCL10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 40)

• vimplicated in apoptosis, and it has been suggested that mutated forms gain oncogenic activity. The occurrence of genomic BCL10 mutations in gastric MALT-type lymphomas was investigated. (PMID:11830492)
• Mutations, relatively common in lymphomas, are extremely rare in malignant cartilaginous tumors. (PMID:11836626)
• REVIEW: Genetic alterations involving BCL10 underlying the pathogenesis of MALT lymphoma (PMID:11960389)
• There is a lack of BCL10 mRNA mutation in lymphold malignancies. (PMID:12017308)
• association of mutations with aberrant BCL10 localization in the nucleus in nasal NK/T-cell lymphomas (PMID:14523480)
• Bcl10 is post-translationally modified by Rip2 and has a role in T-cell signaling (PMID:14638696)
• Nuclear expression of BCL10 is unlikely to correlate with the API2-MALT1 fusion gene in ocular adnexal MALT lymphoma. (PMID:14674990)
• Bcl10 targets NEMO for lysine-63-linked ubiquitination (PMID:14695475)
• Together, these findings suggest that Bcl10 nuclear expression may modulate gene expression and Bcl10 is a potential transcriptional activator apart from its traditional roles that have been found. (PMID:15207693)
• BinCard inhibits BCL10-mediated activation of NF-kappa B. (PMID:15637807)
• The ability of Bcl10 expression to prevent B-cell antigen receptor-induced growth arrest and apoptosis of WEHI-231 cells was dependent on NF-kappaB activation. (PMID:15878976)
• nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor kappaB (NF-kappaB) pathway but also in other biologic functions in lymphocytes (PMID:16123224)
• Accumulation of BCL10 at the perinuclear region is required for the BCL10-mediated NF-kappa B activation. (PMID:16127295)
• TNFalpha up-regulates the expression of Bcl10 and induces a fraction of Bcl10 nuclear translocation in human breast cancer cells: Akt1, activated by TNFalpha, phosphorylates Bcl10 at Ser218 and Ser231 which complexes with Bcl3 to enter the nucleus (PMID:16280327)
• BCL10 immunohistochemistry is a simple technique to identify those MALT lymphoma cases with an underlying genetic aberration. (PMID:16341151)
• results reveal a physiological function of cellular inhibitor of apoptosis 2, identify Bcl10 upregulation as a unifying molecular mechanism for mucosa-associated lymphoid tissue lymphomas. (PMID:16775419)
• Heterogeneous BCL10 gene amplification in diffuse large B cell lymphoma cells. (PMID:16785131)
• Data show that IRAK-1 acts as the essential upstream adaptor that recruits BCL10 to the TLR4 signaling complex and mediates signaling to NF-kappaB through the BCL10-MALT1-TRAF6-TAK1 cascade. (PMID:16831874)
• CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in hepatocytes. (PMID:17101977)
• Bcl10 is a key signaling component mediating NF-kappaB activation induced by GPCRs in nonlymphoid cells. (PMID:17179215)
• BCL10 nuclear expression was present in four of 17 cases od MALT lymphoma. (PMID:17199743)
• Mutants of Bcl10 in the IKK phosphorylation site are resistant to degradation (PMID:17213322)
• These results point to a key role of Bcl10 in F-actin-dependent immune responses of T cells and monocytes/macrophages. (PMID:17371994)
• These findings demonstrate that phosphorylation of Bcl10 at S138 down-regulates Bcl10 protein levels and thus negatively regulates T-cell receptor-mediated NF-kappaB activation. (PMID:17502353)
• Identify Bcl10 as a mediator of LPS-induced activation of NK-kappaB and IL-8. (PMID:17540779)
• Epo has a role in reducing expression of apoptosis-related proteins Bcl-2 and Bcl-10 in ovarian cancer cells (PMID:17893875)
• BCL10 and MALT1 might not only reflect the lymphocytic origin of H-RS cells, but autonomous activity of this crippled antigen receptor pathway might confer NFB activity and apoptosis resistance 9 at least in those cases of HL expressing wild-type IB. (PMID:18231929)
• Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan (PMID:18252714)
• The regulated ubiquitination of Bcl10 and its recognition by NEMO are a critical link between the Carma1-Bcl10-MALT1 complex, IkappaB kinase recruitment, and NF-kappaB activation. (PMID:18287044)
• A novel mutation of Bc1-10 gene in ocular adnexal MALT lymphoma was detected in Chinese patients. (PMID:18307945)
• The bcl-10 staining was most intense in MALT lymphoma of ocular adnexa (PMID:18346354)
• results further define the molecular mechanisms that control activation of NF-kappaB and reveal a function for A20 in the regulation of CARMA and BCL10 activity in lymphoid and non-lymphoid cells (PMID:18349075)
• Data show that the protein kinase C-responsive inhibitory domain of CARD11 functions in NF-kappaB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association. (PMID:18625728)
• analysis of protein domains that mediate interaction between Bcl10 and MALT1 (PMID:18806265)
• BCL10 nuclear expression and t(11;18)(q21;q21)-positive gastric MALT lymphomas are likely to be related to a failure to respond to H. pylori eradication in Chinese patients. (PMID:18949449)
• BCL10 nuclear expression is common in ocular adnexal mucosa-associated lymphoid tissue lymphomas. (PMID:19035248)
• components of the CBM complex, Carma3, Bcl10, and Malt1 are key mediators of the CXCL8/IL8-induced NFkappaB activation and VEGF up-regulation. (PMID:19112107)
• data suggest that this inherent instability of MALT1-API2 prevents its accumulation and renders a potential effect on MALT lymphoma development via destabilization of BCL10 unlikely (PMID:19279678)
• Bcl-10 is expressed in peripheral T-cell lymphomas, correlates with PKC theta and Pp65(Ser536) expression and seems to be associated with better survival. (PMID:19309400)
• T-cell activation triggers the recruitment of the COP9 signalosome (CSN) to the Carma1-Bcl10-Malt1 (CBM) complex, and CSN downregulation impairs TCR-induced IKK activation. (PMID:19444310)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bcl10	ENSMUSG00000028191
rattus_norvegicus	Bcl10	ENSRNOG00000042389

Protein

Protein identifiers

B-cell lymphoma/leukemia 10 — O95999 (reviewed: O95999)

Alternative names: B-cell CLL/lymphoma 10, CARD-containing molecule enhancing NF-kappa-B, CARD-like apoptotic protein, CED-3/ICH-1 prodomain homologous E10-like regulator, Cellular homolog of vCARMEN, Cellular-E10, Mammalian CARD-containing adapter molecule E10

All UniProt accessions (3): O95999, A0A087WWW9, A0A3B3ISX2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation. Acts by channeling adaptive and innate immune signaling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Recruited by activated CARD domain-containing proteins: homooligomerized CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex. This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity. Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK.

Subunit / interactions. Homomultimer; homooligomerized following recruitment by CARD domain-containing proteins that form a nucleating helical template that recruits BCL10 via CARD-CARD interaction. Self-associates by CARD-CARD interaction and interacts with other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14. Forms a complex with CARD14 and MALT1; resulting in the formation of a CBM (CARD14-BCL10-MALT1) complex. Forms a complex with CARD11 and MALT1; resulting in the formation of a CBM (CARD11-BCL10-MALT1) complex. Forms a complex with CARD9 and MALT1; resulting in the formation of a CBM (CARD9-BCL10-MALT1) complex. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Binds caspase-9 with its C-terminal domain. Interacts with TRAF2 and BIRC2/c-IAP2. Interacts with PELI2 and SOCS3; these interactions may be mutually exclusive.

Subcellular location. Cytoplasm. Perinuclear region. Membrane raft.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated. Phosphorylation results in dissociation from TRAF2 and binding to BIRC2/c-IAP2. Phosphorylated by IKBKB/IKKB. Ubiquitinated via both ‘Lys-63’-linked and linear (‘Met-1’-linked) polyubiquitin chains in response to T-cell receptor (TCR) activation. Ubiquitination is recognized by IKBKG/NEMO, the regulatory subunit of I-kappa-B kinase (IKK), and is required for TCR-induced NF-kappa-B activation. Linear ubiquitination at Lys-17, Lys-31 and Lys-63 is mediated by RNF31/HOIP; linear ubiquitination is recognized with much higher affinity than ‘Lys-63’-linked ubiquitin by IKBKG/NEMO. CARD11 is required for linear ubiquitination by HOIP by promoting the targeting of BCL10 to RNF31/HOIP. Proteolytically cleaved by MALT1; required for T-cell activation.

Disease relevance. 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. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001307644, NP_003912* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001315	CARD	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR033238	BCL10/E10	Family
IPR042143	CARD_BCL10	Domain

Pfam: PF00619

UniProt features (63 total): sequence variant 20, mutagenesis site 20, helix 8, turn 3, cross-link 3, modified residue 2, strand 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6BZE	ELECTRON MICROSCOPY	4
8CZO	ELECTRON MICROSCOPY	4.3
8CZD	ELECTRON MICROSCOPY	4.6
6GK2	ELECTRON MICROSCOPY	4.9
2MB9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95999-F1	70.43	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 228–229 (cleavage; by malt1)

Post-translational modifications (5): 1, 138, 17, 31, 63

Mutagenesis-validated functional residues (20):

Position	Phenotype
17	decreased linear ubiquitination and impaired ability to activate nf-kappa-b; when associated with r-31 and r-63.
28	abolishes cell death-inducing capability.
31	decreased ubiquitination and ability to bind nemo; when associated with 63-r–r-67. decreased ubiquitination and ability
36	abolished homomultimerization and formation of a cbm complex, abolished ability to activate nf-kappa-b.
41	abolishes cell death-inducing capability.
41	abolishes nf-kappa-b activation and homo/heterodimerization.
46	abolishes cell death-inducing capability.
47	abolishes cell death-inducing capability.
50–51	abolished homomultimerization and formation of a cbm complex.
50	abolished homomultimerization and formation of a cbm complex, abolished ability to activate nf-kappa-b.
53	abolishes cell death-inducing capability.
53	abolished homomultimerization and formation of a cbm complex, abolished ability to activate nf-kappa-b.
55	abolishes cell death-inducing capability.
63–67	decreased ubiquitination and ability to bind nemo; when associated with r-31.
63	decreased ubiquitination and ability to bind nemo, impaired ability to activate nf-kappa-b; when associated with r-31. d
78	abolishes nf-kappa-b activation.
81–85	complete loss of ikbkb/ikkb-mediated phosphorylation.
105–115	does not affect ubiquitination and ability to bind nemo.
228	abolishes malt1-mediated cleavage.
231	promotes nf-kappa-b activation.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-202403	TCR signaling
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-392499	Metabolism of proteins
R-HSA-5621481	C-type lectin receptors (CLRs)
R-HSA-597592	Post-translational protein modification
R-HSA-8852135	Protein ubiquitination
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 471 (showing top): PID_BCR_5PATHWAY, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_B_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION

GO Biological Process (40): B cell apoptotic process (GO:0001783), neural tube closure (GO:0001843), toll-like receptor signaling pathway (GO:0002224), adaptive immune response (GO:0002250), negative regulation of mature B cell apoptotic process (GO:0002906), cellular defense response (GO:0006968), programmed cell death (GO:0012501), immunoglobulin mediated immune response (GO:0016064), quinolinate biosynthetic process (GO:0019805), positive regulation of protein ubiquitination (GO:0031398), lipopolysaccharide-mediated signaling pathway (GO:0031663), response to food (GO:0032094), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of lymphotoxin A production (GO:0032761), positive regulation of mast cell cytokine production (GO:0032765), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of phosphorylation (GO:0042327), positive regulation of apoptotic process (GO:0043065), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of DNA-templated transcription (GO:0045893), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell receptor signaling pathway (GO:0050862), positive regulation of T cell activation (GO:0050870), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein homooligomerization (GO:0051260), antifungal innate immune response (GO:0061760), T cell apoptotic process (GO:0070231), cellular response to lipopolysaccharide (GO:0071222), cellular response to mechanical stimulus (GO:0071260), apoptotic signaling pathway (GO:0097190), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), positive regulation of cytokine production (GO:0001819), immune system process (GO:0002376), apoptotic process (GO:0006915), response to fungus (GO:0009620), response to lipopolysaccharide (GO:0032496), regulation of apoptotic process (GO:0042981), regulation of T cell receptor signaling pathway (GO:0050856)

GO Molecular Function (13): protease binding (GO:0002020), transcription coactivator activity (GO:0003713), protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein kinase B binding (GO:0043422), protein-containing complex binding (GO:0044877), CARD domain binding (GO:0050700), NF-kappaB binding (GO:0051059), general transcription initiation factor binding (GO:0140296), protein binding (GO:0005515), kinase activator activity (GO:0019209)

GO Cellular Component (13): immunological synapse (GO:0001772), polkadots (GO:0002096), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosome (GO:0005764), cytosol (GO:0005829), cytoplasmic microtubule (GO:0005881), CBM complex (GO:0032449), protein-containing complex (GO:0032991), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	2
Innate Immune System	2
Downstream signaling events of B Cell Receptor (BCR)	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
C-type lectin receptors (CLRs)	1
Protein ubiquitination	1
Signaling by the B Cell Receptor (BCR)	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	4
positive regulation of cytokine production	2
protein binding	2
binding	2
lymphocyte apoptotic process	1
primary neural tube formation	1
tube closure	1
pattern recognition receptor signaling pathway	1
immune response	1
mature B cell apoptotic process	1
negative regulation of B cell apoptotic process	1
regulation of mature B cell apoptotic process	1
defense response	1
signal transduction	1
cell death	1
B cell mediated immunity	1
dicarboxylic acid biosynthetic process	1
quinolinate metabolic process	1
pyridine-containing compound biosynthetic process	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
response to nutrient levels	1
response to chemical	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
lymphotoxin A production	1
regulation of lymphotoxin A production	1
positive regulation of protein metabolic process	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
mast cell cytokine production	1
regulation of mast cell cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
intracellular signaling cassette	1
phosphorylation	1

Protein interactions and networks

STRING

1528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCL10	CARD11	Q9BXL7	999
BCL10	MALT1	Q9UDY8	999
BCL10	CARD9	Q9H257	998
BCL10	CARD10	Q9BWT7	998
BCL10	TRAF6	Q9Y4K3	994
BCL10	CASP8	Q14790	984
BCL10	IKBKG	Q9Y6K9	981
BCL10	CARD14	Q9BXL6	977
BCL10	MIB2	Q96AX9	916
BCL10	PRKCQ	Q04759	902
BCL10	RIGI	O95786	893
BCL10	IKBKB	O14920	876
BCL10	SYK	P43405	868
BCL10	NFKB1	P19838	848
BCL10	CHUK	O15111	843

IntAct

121 interactions, top by confidence:

A	B	Type	Score
MALT1	BCL10	psi-mi:“MI:0914”(association)	0.950
BCL10	MALT1	psi-mi:“MI:0915”(physical association)	0.950
MALT1	BCL10	psi-mi:“MI:0915”(physical association)	0.950
CARD11	BCL10	psi-mi:“MI:0915”(physical association)	0.860
BCL10	CARD11	psi-mi:“MI:0914”(association)	0.860
BCL10	CARD11	psi-mi:“MI:0915”(physical association)	0.860
CARD11	BCL10	psi-mi:“MI:0914”(association)	0.860
TRAF2	BCL10	psi-mi:“MI:0915”(physical association)	0.850
BCL10	TRAF2	psi-mi:“MI:0915”(physical association)	0.850
BCL10	TRAF2	psi-mi:“MI:0914”(association)	0.850
BCL10	IKBKG	psi-mi:“MI:0915”(physical association)	0.790

BioGRID (224): MALT1 (Affinity Capture-Western), MALT1 (Reconstituted Complex), UBE2V2 (Reconstituted Complex), IKBKG (Reconstituted Complex), CHUK (Reconstituted Complex), IKBKB (Reconstituted Complex), UBE2N (Reconstituted Complex), BCL10 (Two-hybrid), BCL10 (Two-hybrid), BCL10 (Proximity Label-MS), BCL10 (Affinity Capture-MS), BCL10 (Affinity Capture-MS), CARD11 (Affinity Capture-Western), MALT1 (Affinity Capture-Western), BCL10 (Affinity Capture-Western)

ESM2 similar proteins: A7YWH3, E1BP74, E2RK09, F1SRY5, G3X8Y1, O15151, O95999, P86174, P97432, Q00IB7, Q13023, Q17RG1, Q3UFT3, Q501R9, Q562E2, Q5PQN5, Q5RC94, Q5SUE8, Q5SXH7, Q5XIN1, Q6AI12, Q6NRE4, Q6ZPF3, Q6ZU67, Q7TP65, Q7ZVU1, Q810L3, Q86T82, Q86XL3, Q8BFU3, Q8BJ34, Q8BSV3, Q8C0R0, Q8IVF5, Q8IW35, Q8N7W2, Q8ND24, Q8NDB2, Q8TEW8, Q8VIG2

Diamond homologs: O95999, Q66677, Q9QYN5, Q9Z0H7

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
BCL10	up-regulates	IKBKG	binding
CARD9	“up-regulates quantity by stabilization”	BCL10	binding
ITCH	“down-regulates quantity by destabilization”	BCL10	ubiquitination
BCL10	“up-regulates quantity by expression”	NFKB1	“transcriptional regulation”
IKBKG	“up-regulates activity”	BCL10	ubiquitination
IKBKB	“up-regulates activity”	BCL10	phosphorylation
BCL10	“form complex”	CBM	binding
ATM	“up-regulates activity”	BCL10	phosphorylation
RNF8	“up-regulates quantity by stabilization”	BCL10	ubiquitination
CARD11	up-regulates	BCL10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NOD1/2 Signaling Pathway	5	45.3×	1e-05
C-type lectin receptors (CLRs)	6	40.8×	1e-06
Regulation of TNFR1 signaling	5	32.0×	3e-05
CLEC7A (Dectin-1) signaling	7	28.6×	1e-06
FCERI mediated NF-kB activation	5	22.4×	1e-04
Downstream TCR signaling	6	22.0×	2e-05
Innate Immune System	8	5.8×	1e-03
Viral Infection Pathways	6	5.3×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	7	57.0×	8e-09
positive regulation of interleukin-2 production	5	52.0×	8e-06
obsolete positive regulation of NF-kappaB transcription factor activity	9	41.1×	3e-10
negative regulation of canonical NF-kappaB signal transduction	6	22.9×	4e-05
positive regulation of canonical NF-kappaB signal transduction	13	21.0×	2e-11
regulation of apoptotic process	7	13.0×	1e-04
positive regulation of ERK1 and ERK2 cascade	5	9.5×	7e-03
negative regulation of apoptotic process	8	6.2×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — DLBCLNOS, MLYM.

Clinical variants and AI predictions

ClinVar

145 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	1
Uncertain significance	54
Likely benign	50
Benign	6

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
160347	NM_003921.5(BCL10):c.57+1G>A	Pathogenic
1968159	NM_003921.5(BCL10):c.14dup (p.Pro6fs)	Pathogenic
2086361	NM_003921.5(BCL10):c.217C>T (p.Gln73Ter)	Pathogenic
30361	NM_003921.5(BCL10):c.488C>T (p.Thr163Met)	Pathogenic
3651130	NM_003921.5(BCL10):c.207dup (p.Asp70fs)	Pathogenic
4691162	NM_003921.5(BCL10):c.262C>T (p.Arg88Ter)	Pathogenic
6250	NM_003921.5(BCL10):c.499dup (p.Ser167fs)	Pathogenic
6251	NM_003921.5(BCL10):c.163dup (p.Ile55fs)	Pathogenic
6252	NM_003921.5(BCL10):c.345del (p.Gly116fs)	Pathogenic
6253	NM_003921.5(BCL10):c.427_428dup (p.Glu145fs)	Pathogenic
6254	NM_003921.5(BCL10):c.231dup (p.Gly78fs)	Pathogenic
6255	NM_003921.5(BCL10):c.525_541del (p.Val176fs)	Pathogenic
6256	NM_003921.5(BCL10):c.410del (p.Asn137fs)	Pathogenic
6257	NM_003921.5(BCL10):c.398dup (p.Ser134fs)	Pathogenic
6258	NM_003921.5(BCL10):c.629AAG[2] (p.Glu212del)	Pathogenic
6259	NM_003921.5(BCL10):c.136dup (p.Ile46fs)	Pathogenic
6260	NM_003921.5(BCL10):c.428del (p.Phe143fs)	Pathogenic
6263	NM_003921.5(BCL10):c.136del (p.Ile46fs)	Pathogenic
6265	NM_003921.5(BCL10):c.172C>G (p.Arg58Gly)	Pathogenic
6266	NM_003921.5(BCL10):c.172C>T (p.Arg58Ter)	Pathogenic
1807732	GRCh37/hg19 1p22.3(chr1:85667594-85875622)x3	Likely pathogenic

SpliceAI

460 predictions. Top by Δscore:

Variant	Effect	Δscore
1:85270612:TCTTA:T	donor_loss	1.0000
1:85270613:CTTA:C	donor_loss	1.0000
1:85270614:TTAC:T	donor_loss	1.0000
1:85270615:TACC:T	donor_loss	1.0000
1:85270616:A:AC	donor_gain	1.0000
1:85270616:A:AT	donor_loss	1.0000
1:85270617:C:CC	donor_gain	1.0000
1:85270617:CCTTT:C	donor_gain	1.0000
1:85270907:C:CG	acceptor_loss	1.0000
1:85276294:A:AC	donor_gain	1.0000
1:85276294:ACGT:A	donor_gain	1.0000
1:85276295:C:CC	donor_gain	1.0000
1:85276295:CGTC:C	donor_gain	1.0000
1:85276297:T:TA	donor_gain	1.0000
1:85270616:AC:A	donor_gain	0.9900
1:85270617:CC:C	donor_gain	0.9900
1:85270903:AGGC:A	acceptor_gain	0.9900
1:85270903:AGGCC:A	acceptor_gain	0.9900
1:85270904:GGC:G	acceptor_gain	0.9900
1:85270904:GGCCT:G	acceptor_gain	0.9900
1:85270905:GC:G	acceptor_gain	0.9900
1:85270905:GCC:G	acceptor_gain	0.9900
1:85270906:CC:C	acceptor_gain	0.9900
1:85270906:CCT:C	acceptor_gain	0.9900
1:85270907:C:CC	acceptor_gain	0.9900
1:85270907:CT:C	acceptor_gain	0.9900
1:85270908:T:A	acceptor_gain	0.9900
1:85276295:CGT:C	donor_gain	0.9900
1:85270659:T:TA	donor_gain	0.9800
1:85276294:ACGTC:A	donor_gain	0.9800

AlphaMissense

1502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:85270682:G:C	F94L	0.999
1:85270682:G:T	F94L	0.999
1:85270684:A:G	F94L	0.999
1:85270711:A:G	S85P	0.999
1:85270719:A:G	L82P	0.999
1:85270732:C:G	G78R	0.999
1:85270758:A:G	L69S	0.999
1:85270761:A:G	L68S	0.999
1:85270824:A:G	L47P	0.999
1:85270824:A:T	L47H	0.999
1:85270840:G:T	R42S	0.999
1:85270842:A:G	L41P	0.999
1:85270842:A:T	L41Q	0.999
1:85270863:G:T	A34D	0.999
1:85270668:A:C	I99S	0.998
1:85270707:A:T	I86N	0.998
1:85270710:G:A	S85F	0.998
1:85270719:A:T	L82H	0.998
1:85270749:A:G	L72S	0.998
1:85270854:T:C	H37R	0.998
1:85270856:T:A	R36S	0.998
1:85270856:T:G	R36S	0.998
1:85270881:A:G	L28P	0.998
1:85270881:A:T	L28Q	0.998
1:85276302:C:A	K17N	0.998
1:85276302:C:G	K17N	0.998
1:85270668:A:G	I99T	0.997
1:85270668:A:T	I99N	0.997
1:85270683:A:G	F94S	0.997
1:85270728:A:G	L79P	0.997

dbSNP variants (sampled 300 via entrez): RS1000224153 (1:85265605 A>G), RS1000355808 (1:85268360 G>A), RS1000383283 (1:85275929 G>A,C), RS1000664692 (1:85277909 A>C,G), RS1000718516 (1:85276707 G>C,T), RS1000749528 (1:85276582 C>G,T), RS1000780363 (1:85277591 C>T), RS1000997882 (1:85270099 T>A), RS1001940315 (1:85277018 A>G), RS1002365480 (1:85271680 C>T), RS1002651998 (1:85273162 T>C), RS1002655078 (1:85274593 C>T), RS1002791293 (1:85278550 C>G,T), RS1002920263 (1:85273532 T>A), RS1003033629 (1:85274879 T>C)

Disease associations

OMIM: gene MIM:603517 | disease phenotypes: MIM:616098, MIM:615546, MIM:137245, MIM:156240, MIM:273300, MIM:605027

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 37	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 37	Definitive	AR

Mondo (12): immunodeficiency 37 (MONDO:0014491), testicular cancer (MONDO:0005447), van Maldergem syndrome 2 (MONDO:0014242), mesothelioma (MONDO:0005065), MALT lymphoma (MONDO:0007650), follicular lymphoma (MONDO:0018906), colon carcinoma (MONDO:0002032), T-cell acute lymphoblastic leukemia (MONDO:0004963), Sezary syndrome (MONDO:0017844), malignant mesothelioma (MONDO:0006292), testicular germ cell tumor (MONDO:0010108), lymphoma, non-Hodgkin, familial (MONDO:0011508)

Orphanet (6): Cerebrofacioarticular syndrome (Orphanet:314679), MALT lymphoma (Orphanet:52417), Follicular lymphoma (Orphanet:545), Sézary syndrome (Orphanet:3162), Germ cell tumor of testis (Orphanet:363504), Pleural mesothelioma (Orphanet:50251)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000505	Visual impairment
HP:0000614	Abnormal nasolacrimal system morphology
HP:0000820	Abnormality of the thyroid gland
HP:0000975	Hyperhidrosis
HP:0001250	Seizure
HP:0001442	Typified by somatic mosaicism
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001945	Fever
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002113	Pulmonary infiltrates
HP:0002133	Status epilepticus
HP:0002205	Recurrent respiratory infections
HP:0002383	Infectious encephalitis
HP:0002583	Colitis
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0002898	Embryonal neoplasm
HP:0003581	Adult onset
HP:0003593	Infantile onset
HP:0003745	Sporadic
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0006254	Elevated circulating alpha-fetoprotein concentration
HP:0009792	Teratoma

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005531_27	Multiple sclerosis	1.000000e-20
GCST009391_1534	Metabolite levels	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010510	NG-monomethyl-arginine measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008224	Lymphoma, Follicular	C04.557.386.480.350; C15.604.515.569.480.350; C20.683.515.761.480.350
D008654	Mesothelioma	C04.557.470.035.510; C04.557.470.660.510
D012751	Sezary Syndrome	C04.557.386.480.750.800.775; C15.604.515.569.480.750.800.775; C15.604.515.841; C20.683.515.761.480.750.800.775; C20.683.515.920
D013736	Testicular Neoplasms	C04.588.322.762; C04.588.945.440.915; C12.100.500.260.937; C12.200.294.260.937; C12.200.758.409.937; C12.900.619.937; C19.344.762; C19.391.829.782
C563236	Testicular Germ Cell Tumor (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
Arsenic	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cyclosporine	increases expression	2
Gold Compounds	decreases expression, increases methylation, affects cotreatment, increases expression	2
Genistein	decreases reaction, increases expression	2
2-anisidine	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
VX-agent	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
usnic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
EKB 569	decreases expression	1
abrine	increases expression	1
3,5-bis(2-fluorobenzylidene)piperidin-4-one	increases expression, decreases reaction	1
jinfukang	decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Aripiprazole	increases expression, affects cotreatment	1
Resveratrol	decreases reaction, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Capsaicin	increases expression	1
Carmustine	increases expression	1

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1L4	Abcam HeLa BCL10 KO	Cancer cell line	Female
CVCL_B8BU	Abcam HCT 116 BCL10 KO	Cancer cell line	Male
CVCL_B8ST	Abcam MCF-7 BCL10 KO	Cancer cell line	Female
CVCL_B9DY	Abcam A-549 BCL10 KO	Cancer cell line	Male
CVCL_E1RZ	HAP1 BCL10 (-) 1	Cancer cell line	Male
CVCL_E1S0	HAP1 BCL10 (-) 2	Cancer cell line	Male
CVCL_E1S1	HAP1 BCL10 (-) 3	Cancer cell line	Male
CVCL_E1S2	HAP1 BCL10 (-) 4	Cancer cell line	Male
CVCL_F1R5	HyCyte Jurkat KO-hBCL10	Cancer cell line	Male

Clinical trials (associated diseases)

297 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01641172	PHASE4	COMPLETED	Taste, Smell and Chemotherapy (TASTY)
NCT03655821	PHASE4	TERMINATED	Dose Individualization of Pemetrexed - IMPROVE-II
NCT03655834	PHASE4	COMPLETED	Dose Individualization of Pemetrexed - IMPROVE-III
NCT03656549	PHASE4	COMPLETED	Dose Individualization of Pemetrexed - IMPROVE-I
NCT06010277	PHASE4	UNKNOWN	Folinic Acid for Prevention of Pemetrexed-induced Toxicity
NCT06593665	PHASE3	RECRUITING	Intrathecal Morphine Versus Intravenous Methadone for Postoperative Analgesia Following Retroperitoneal Lymph Node Dissection.
NCT00128102	PHASE3	COMPLETED	Suberoylanilide Hydroxamic Acid (Vorinostat, MK-0683) Versus Placebo in Advanced Malignant Pleural Mesothelioma (MK-0683-014)
NCT00190762	PHASE3	COMPLETED	A Study Comparing Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Alone in the Treatment of Mesothelioma
NCT01604005	PHASE3	TERMINATED	PIT: Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma
NCT02511600	PHASE3	WITHDRAWN	Comparison of Progel Sealant to Standard of Care (SOC) for Patients Undergoing Decortication
NCT02899299	PHASE3	COMPLETED	Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients
NCT03063450	PHASE3	COMPLETED	CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma
NCT04334759	PHASE3	COMPLETED	DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
NCT00183820	PHASE2	COMPLETED	Study of Gemcitabine, Oxaliplatin, and Paclitaxel in Patients With Refractory Germ Cell Carcinoma
NCT00531687	PHASE2	TERMINATED	Trial of Paclitaxel, Gemcitabine and Cisplatin in Patients With Relapsing Germ Cell Cancer
NCT00587964	PHASE2	COMPLETED	Phase II Trial of Stereotactic Radiosurgery Boost Following Surgical Resection for Brain Metastases
NCT00772694	PHASE2	UNKNOWN	Sorafenib Monotherapy in Inoperable/Recurrent Germ Cell Carcinoma Refractory to Chemotherapy
NCT00936936	PHASE2	COMPLETED	High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors
NCT00957905	PHASE2	COMPLETED	Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
NCT01242631	PHASE2	COMPLETED	Everolimus for Patients With Relapsed/Refractory Germ Cell Cancer
NCT01684098	PHASE2	COMPLETED	Safety and Efficacy of FalateScan (Technetium Tc 99m EC20) in Patients With Known Suspected Recurrent or Metastatic Cancer From a Solid Tumor
NCT02478502	PHASE2	TERMINATED	Testis CAB: Cabazitaxel as Salvage Treatment for Cisplatin-resistant Germ Cell Cancer
NCT02689219	PHASE2	TERMINATED	Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
NCT02860819	PHASE2	COMPLETED	Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer
NCT03339635	PHASE2	COMPLETED	Short-term Testosterone Replacement in Testicular Cancer Survivors
NCT03937843	PHASE2	ACTIVE_NOT_RECRUITING	Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma
NCT04150848	PHASE2	UNKNOWN	A Biobehavioral Intervention for Young Men With Testicular Cancer
NCT05969860	PHASE2	RECRUITING	At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
NCT06684327	PHASE2	RECRUITING	Multi-cohort, Single-arm Phase II Study of Albumin-paclitaxel, Ifosfamide, and Cisplatin in the Treatment of Rare Advanced Tumors
NCT06866964	PHASE2	RECRUITING	A Single-arm, Phase II Clinical Trial of ASPIRin to prEvent Venous Thromboembolism in Patients With Advanced Germ Cell Tumors Receiving Chemotherapy
NCT06932458	PHASE2	RECRUITING	A Clinical Trial of Primary Retroperitoneal Lymph Node Dissection in Patients With Testicular Seminoma With Limited Retroperitoneal Metastases
NCT07568444	PHASE2	COMPLETED	Enhancing Readability of Lay Abstracts and Summaries for Medical Knowledge Using Generative Artificial Intelligence (BRIDGE AI 3)
NCT00004547	PHASE2	COMPLETED	Treatment of Peritoneal Cancer With Surgery, Perfused Heated Cisplatin and Chemotherapy
NCT00061477	PHASE2	COMPLETED	Pemetrexed Plus Gemcitabine as Front-Line Chemotherapy for Patients With Malignant Pleural or Peritoneal Mesothelioma
NCT00101283	PHASE2	COMPLETED	Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma
NCT00137826	PHASE2	COMPLETED	Bevacizumab (Avastin) and Erlotinib (Tarceva) in Previously Treated Mesothelioma
NCT00295503	PHASE2	COMPLETED	Cisplatin, Pemetrexed and Bevacizumab for Untreated Malignant Mesothelioma
NCT00316225	PHASE2	COMPLETED	Study of Pemetrexed in Mesothelioma and Lung Cancer Patients With Fluid Around the Lungs or Abdomen
NCT00407459	PHASE2	COMPLETED	Phase II Study of Bevacizumab, Pemetrexed and Carboplatin as First-Line Therapy in Malignant Pleural Mesothelioma
NCT00454519	PHASE2	UNKNOWN	Surgery Plus Intraoperative Peritoneal Hyperthermic Chemotherapy (IPHC) to Treat Peritoneal Carcinomatosis