MALT1

Summary

MALT1 (MALT1 paracaspase, HGNC:6819) is a protein-coding gene on chromosome 18q21.32, encoding Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Q9UDY8). Protease that enhances BCL10-induced activation: acts via formation of CBM complexes that channel adaptive and innate immune signaling downstream of CARD domain-containing proteins (CARD9, CARD11 and CARD14) to activate NF-kappa-B and MAP kinase p38 pathways which stimulate expr….

This gene encodes a caspase-like protease that plays a role in BCL10-induced activation of NF-kappaB. The protein is a component of the CARMA1-BCL10-MALT1 (CBM) signalosome that triggers NF-kappaB signaling and lymphoctye activation following antigen-receptor stimulation. Mutations in this gene result in immunodeficiency 12 (IMD12). This gene has been found to be recurrently rearranged in chromosomal translocations with other genes in mucosa-associated lymphoid tissue lymphomas, including a t(11;18)(q21;q21) translocation with the baculoviral IAP repeat-containing protein 3 (also known as apoptosis inhibitor 2) locus [BIRC3(API2)-MALT1], and a t(14;18)(q32;q21) translocation with the immunoglobulin heavy chain locus (IGH-MALT1). Alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 10892 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency due to MALT1 deficiency (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 454 total — 16 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006785

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6819
Approved symbol	MALT1
Name	MALT1 paracaspase
Location	18q21.32
Locus type	gene with protein product
Status	Approved
Aliases	PCASP1
Ensembl gene	ENSG00000172175
Ensembl biotype	protein_coding
OMIM	604860
Entrez	10892

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 13 protein_coding, 10 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000345724, ENST00000587438, ENST00000589873, ENST00000591792, ENST00000648670, ENST00000649125, ENST00000649202, ENST00000649217, ENST00000649756, ENST00000650045, ENST00000650355, ENST00000697044, ENST00000697045, ENST00000697046, ENST00000697098, ENST00000697099, ENST00000851939, ENST00000851940, ENST00000851941, ENST00000968608, ENST00000968609, ENST00000968610, ENST00000968611, ENST00000968612, ENST00000968613, ENST00000968614

RefSeq mRNA: 2 — MANE Select: NM_006785 NM_006785, NM_173844

CCDS: CCDS11967, CCDS11968

Canonical transcript exons

ENST00000649217 — 17 exons

Exon	Start	End
ENSE00001144898	58696366	58696487
ENSE00001159625	58734307	58734381
ENSE00001159634	58733397	58733574
ENSE00001159640	58723048	58723251
ENSE00001159645	58715935	58715967
ENSE00001159649	58714083	58714109
ENSE00001159656	58710921	58710953
ENSE00001159661	58709976	58710072
ENSE00001159666	58709378	58709556
ENSE00001159671	58700441	58700591
ENSE00001331691	58747405	58754477
ENSE00003504195	58745666	58745791
ENSE00003611933	58681170	58681336
ENSE00003656071	58744338	58744495
ENSE00003685940	58741865	58742014
ENSE00003690943	58735202	58735329
ENSE00003837623	58671465	58671852

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 91.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2860 / max 554.2359, expressed in 1705 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170431	6.6654	1571
170429	6.3889	1398
170430	1.1868	506
170427	0.5716	335
170428	0.4306	210
170426	0.0427	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	91.81	gold quality
tonsil	UBERON:0002372	91.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.51	gold quality
calcaneal tendon	UBERON:0003701	90.43	gold quality
monocyte	CL:0000576	89.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.43	gold quality
mononuclear cell	CL:0000842	89.41	gold quality
leukocyte	CL:0000738	89.33	gold quality
lymph node	UBERON:0000029	88.95	gold quality
buccal mucosa cell	CL:0002336	88.25	gold quality
vermiform appendix	UBERON:0001154	88.17	gold quality
stromal cell of endometrium	CL:0002255	87.93	gold quality
prostate gland	UBERON:0002367	87.92	gold quality
lower esophagus mucosa	UBERON:0035834	87.31	gold quality
esophagus mucosa	UBERON:0002469	87.30	gold quality
metanephros cortex	UBERON:0010533	86.93	gold quality
cervix squamous epithelium	UBERON:0006922	86.51	gold quality
parotid gland	UBERON:0001831	86.04	gold quality
bone marrow cell	CL:0002092	85.77	gold quality
gastrocnemius	UBERON:0001388	85.55	gold quality
vagina	UBERON:0000996	85.20	gold quality
oral cavity	UBERON:0000167	85.18	gold quality
tendon	UBERON:0000043	85.11	gold quality
granulocyte	CL:0000094	84.80	gold quality
muscle of leg	UBERON:0001383	84.78	gold quality
zone of skin	UBERON:0000014	84.76	gold quality
rectum	UBERON:0001052	84.72	gold quality
skin of abdomen	UBERON:0001416	84.70	gold quality
skin of leg	UBERON:0001511	84.68	gold quality
gall bladder	UBERON:0002110	84.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	390.12
E-MTAB-6142	no	93.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

102 targeting MALT1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-LET-7A-3P	100.00	74.03	3932
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1297	99.91	73.41	3162

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• REVIEW: Genetic alterations involving MALT1 underlying the pathogenesis of MALT lymphoma (PMID:11960389)
• Fuses with API2 and defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. (PMID:12651604)
• translocations t(11;18)(q21;q21) and t(14;18)(q21;q32) represent the main structural aberrations involving MLT/MALT1 in MALT lymphomas, whereas true amplifications of MLT/MALT1 occur rarely in MZBCL (PMID:12931213)
• copy numbers of API2-MALT1 do not reflect tumor cell proportions, and that the number of copies of API2-MALT1 in a tumor cell is different for each clinical sample. (PMID:14562112)
• MALT1 chromosome rearrangements have a role in MALT gastric lymphomas in patients with Sjogren’s syndrome (PMID:14760068)
• Translocation breakpoint never exceeded 2.5% in B-cell lymphoma (PMID:15191563)
• Detection of API2-MALT1 fusion transcripts is useful for evaluating the prognosis and clinical behavior of the MALT lymphoma. (PMID:15363040)
• NF-kappa B signaling, once activated in a CD40-dependent immune response, is maintained and enhanced through deregulation of MALT1 or formation of an API2-MALT1 fusion. (PMID:15598810)
• API2-MALT1 transcript was confirmed to be associated with the levels of apoptosis and API2 of MALT lymphoma. (PMID:15696476)
• Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas. (PMID:15982633)
• 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)
• Study further supports the close interaction between the MALT1 and BCL10 proteins in the pathogenesis of MALT lymphomas. (PMID:16341151)
• Common translocation in MALT lymphoma results in a fusion of the cIAP2 region on chromosome 11q21 with the MALT1 gene on chromosome 18q21. (PMID:16395399)
• Chromosomal translocations leads to upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. (PMID:16395405)
• This study demonstrates that translocations involving MALT1, including IGH/MALT1, are uncommon in cutaneous MALT lymphomas and primary cutaneous DLBCL. (PMID:16630178)
• MALT1-MAP4 fusion does not result in activation of NF-kappa B as with other MALT1-associated translocations. (PMID:16804917)
• the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB independently of TRAF1 AND TRAF2 and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity (PMID:16891304)
• CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in hepatocytes. (PMID:17101977)
• In vivo data indicate an effect of API2-MALT1 expression on the normal immune response of transgenic mice. (PMID:17145608)
• Our results suggest that MALT1-specific translocations and FOXP1 rearrangements are not commonly involved in pathogenesis. (PMID:17199743)
• careful observation for development of gastric carcinoma and disease progression is essential during follow-up of API2-MALT1-positive MALT lymphoma when patients decline second-line treatment. (PMID:17894851)
• Upon T-cell activation, Malt1 is ubiquitinated, which is critical for the engagement of Carma1-Bcl10-Malt1 and IKK complexes, thereby directing T cell receptor signals to the NF-kappaB pathway. (PMID:17948050)
• 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)
• chromosome region 18q21 gain including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma (PMID:18367485)
• 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)
• Caspase-8 undergoes limited activation upon antigenic stimulation, and this activation is dependent on the paracaspase MALT1. (PMID:18691973)
• analysis of protein domains that mediate interaction between Bcl10 and MALT1 (PMID:18806265)
• Methylation and API2/MALT1 fusion in colorectal extranodal marginal zone lymphoma. (PMID:19060847)
• 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)
• TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes and resistance to apoptosis. (PMID:19234489)
• 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)
• data does not support the hypothesis that germline variations of MALT1 may play a role as genetic risk factors in the development of primary gastric lymphoma. (PMID:19394813)
• 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)
• A20 functions as a Malt1 deubiquitinating enzyme and proteasomal degradation and de novo synthesis of A20 contributes to balance T cell receptor/CD28-induced IKK/NF-kappaB signaling (PMID:19494296)
• These results indicate a growth-promoting role for MALT1 paracaspase activity in activated B cell like-diffuse large B cell lymphoma. (PMID:19841089)
• Results demonstrate a key role for MALT1 in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy. (PMID:19897720)
• The molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)-positive mucosa-associated lymphoid tissue lymphomas, is reported. (PMID:19965626)
• API2-MALT1 fusion gene is a distinctive genetic aberration in MALT lymphomas, and is not present in diffuse large B cell lymphoma. (PMID:20079017)
• activation of NF-kappaB by CXCR4 occurs through Carma3/Bcl10/Malt1 (CBM) complex in OSCC. loss of components of CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha. (PMID:20695076)
• A20 is cleaved by MALT1 with the realease of the hA20p50 and hA20p37 fragments. (PMID:20804738)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	malt1	ENSDARG00000077768
mus_musculus	Malt1	ENSMUSG00000032688
rattus_norvegicus	Malt1	ENSRNOG00000017181
caenorhabditis_elegans		WBGENE00017702

Protein

Protein identifiers

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 — Q9UDY8 (reviewed: Q9UDY8)

Alternative names: MALT lymphoma-associated translocation, Paracaspase

All UniProt accessions (4): Q9UDY8, A0A3B3IS32, A0A3B3IS82, K7EP42

UniProt curated annotations — full annotation on UniProt →

Function. Protease that enhances BCL10-induced activation: acts via formation of CBM complexes that channel adaptive and innate immune signaling downstream of CARD domain-containing proteins (CARD9, CARD11 and CARD14) to activate NF-kappa-B and MAP kinase p38 pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines. Mediates BCL10 cleavage: MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion. Involved in the induction of T helper 17 cells (Th17) differentiation. Cleaves RC3H1 and ZC3H12A in response to T-cell receptor (TCR) stimulation which releases their cooperatively repressed targets to promote Th17 cell differentiation. Also mediates cleavage of N4BP1 in T-cells following TCR-mediated activation, leading to N4BP1 inactivation. May also have ubiquitin ligase activity: binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity.

Subunit / interactions. Homooligomer; forms oligomers which bind to TRAF6. 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.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus.

Tissue specificity. Highly expressed in peripheral blood mononuclear cells. Detected at lower levels in bone marrow, thymus and lymph node, and at very low levels in colon and lung.

Disease relevance. Immunodeficiency 12 (IMD12) [MIM:615468] A primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations include mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Levels of absolute lymphocytes and serum immunoglobulins are normal, but specific antibody titers are low despite immunization, and T-cells show impaired proliferative responses to mitogens. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Similarity. Belongs to the peptidase C14B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UDY8-1	1	yes
Q9UDY8-2	2

RefSeq proteins (2): NP_006776, NP_776216 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001309	Pept_C14_p20	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR011600	Pept_C14_caspase	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR029030	Caspase-like_dom_sf	Homologous_superfamily
IPR033540	MALT1_IG-like_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR037940	MALT1_Death	Domain
IPR041077	MALT1_Ig	Domain
IPR052039	Caspase-related_regulators	Family

Pfam: PF00656, PF13895, PF13927, PF18703

UniProt features (95 total): strand 39, helix 25, site 5, turn 5, domain 3, mutagenesis site 3, active site 2, modified residue 2, disulfide bond 2, sequence variant 2, region of interest 2, initiator methionine 1, chain 1, splice variant 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
3BFO	X-RAY DIFFRACTION	1.15
3UOA	X-RAY DIFFRACTION	1.75
3V55	X-RAY DIFFRACTION	1.81
3UO8	X-RAY DIFFRACTION	1.9
9BP2	X-RAY DIFFRACTION	2.01
3V4O	X-RAY DIFFRACTION	2.1
8J5I	X-RAY DIFFRACTION	2.1
7A41	X-RAY DIFFRACTION	2.13
7PAW	X-RAY DIFFRACTION	2.19
7PAV	X-RAY DIFFRACTION	2.2
7AK0	X-RAY DIFFRACTION	2.32
9MKE	X-RAY DIFFRACTION	2.34
4I1P	X-RAY DIFFRACTION	2.4
6F7I	X-RAY DIFFRACTION	2.43
9MKD	X-RAY DIFFRACTION	2.45
8V4X	X-RAY DIFFRACTION	2.49
7AK1	X-RAY DIFFRACTION	2.51
6YN9	X-RAY DIFFRACTION	2.56
6H4A	X-RAY DIFFRACTION	2.65
2G7R	X-RAY DIFFRACTION	2.7
4I1R	X-RAY DIFFRACTION	2.7
3K0W	X-RAY DIFFRACTION	2.8
9MKC	X-RAY DIFFRACTION	2.8
6YN8	X-RAY DIFFRACTION	3.05
8CZO	ELECTRON MICROSCOPY	4.3
6GK2	ELECTRON MICROSCOPY	4.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDY8-F1	80.09	0.56

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 (7): 464; 126–127 (breakpoint for translocation to form birc2-malt1); 216–217 (breakpoint for translocation to form birc2-malt1); 320–321 (breakpoint for translocation to form birc2-malt1); 323–324 (breakpoint for translocation to form birc2-malt1); 329–330 (breakpoint for translocation to form birc2-malt1); 415

Post-translational modifications (2): 2, 135

Disulfide bonds (2): 147–190, 248–290

Mutagenesis-validated functional residues (3):

Position	Phenotype
464	slight decrease in nf-kappa-b activation.
653	abolishes binding to traf6.
806	abolishes binding to traf6.

Function

Pathways and Gene Ontology

Reactome pathways

13 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-5660668	CLEC7A/inflammasome pathway
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-5621481	C-type lectin receptors (CLRs)
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 477 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (27): B-1 B cell differentiation (GO:0001923), positive regulation of T cell cytokine production (GO:0002726), proteolysis (GO:0006508), defense response (GO:0006952), response to fungus (GO:0009620), positive regulation of protein ubiquitination (GO:0031398), lipopolysaccharide-mediated signaling pathway (GO:0031663), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-2 production (GO:0032743), T cell proliferation (GO:0042098), B cell activation (GO:0042113), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), T cell receptor signaling pathway (GO:0050852), regulation of T cell receptor signaling pathway (GO:0050856), nuclear export (GO:0051168), obsolete proteolysis involved in protein catabolic process (GO:0051603), positive regulation of T-helper 17 cell differentiation (GO:2000321), immune system process (GO:0002376), positive regulation of immune effector process (GO:0002699), positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains (GO:0002824), regulation of signal transduction (GO:0009966), positive regulation of T cell activation (GO:0050870), positive regulation of multicellular organismal process (GO:0051240), cellular response to lipopolysaccharide (GO:0071222)

GO Molecular Function (11): protease binding (GO:0002020), endopeptidase activity (GO:0004175), cysteine-type endopeptidase activity (GO:0004197), ubiquitin-protein transferase activity (GO:0004842), peptidase activity (GO:0008233), small molecule binding (GO:0036094), identical protein binding (GO:0042802), endopeptidase activator activity (GO:0061133), protein binding (GO:0005515), hydrolase activity (GO:0016787), kinase activator activity (GO:0019209)

GO Cellular Component (8): fibrillar center (GO:0001650), polkadots (GO:0002096), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), CBM complex (GO:0032449), protein-containing complex (GO:0032991), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-9 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
CLEC7A (Dectin-1) signaling	1
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
apoptotic process	2
endopeptidase activity	2
binding	2
mature B cell differentiation	1
T cell cytokine production	1
positive regulation of T cell mediated immunity	1
positive regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
protein metabolic process	1
response to stress	1
response to other organism	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
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
positive regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
T cell activation	1
lymphocyte proliferation	1
lymphocyte activation	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
antigen receptor-mediated signaling pathway	1
T cell receptor signaling pathway	1
regulation of antigen receptor-mediated signaling pathway	1
nucleocytoplasmic transport	1
intercellular transport	1

Protein interactions and networks

STRING

1606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MALT1	CARD11	Q9BXL7	999
MALT1	BCL10	O95999	999
MALT1	CARD9	Q9H257	997
MALT1	CARD10	Q9BWT7	996
MALT1	TRAF6	Q9Y4K3	994
MALT1	CASP8	Q14790	974
MALT1	IKBKG	Q9Y6K9	952
MALT1	CARD14	Q9BXL6	853
MALT1	BIRC3	Q13489	829
MALT1	CLEC7A	Q9BXN2	797
MALT1	SYK	P43405	773
MALT1	IKBKB	O14920	772
MALT1	PRKCQ	Q04759	769
MALT1	REL	Q04864	719
MALT1	TNFAIP3	P21580	716

IntAct

90 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
BCL10	CARD11	psi-mi:“MI:0914”(association)	0.860
BCL10	TRAF2	psi-mi:“MI:0914”(association)	0.850
MALT1	TRAF6	psi-mi:“MI:0915”(physical association)	0.690
TRAF6	MALT1	psi-mi:“MI:0915”(physical association)	0.690
IKBKG	MALT1	psi-mi:“MI:0915”(physical association)	0.660
MALT1	IKBKG	psi-mi:“MI:0915”(physical association)	0.660
TRIB1	DET1	psi-mi:“MI:0914”(association)	0.640
CARD11	MALT1	psi-mi:“MI:0915”(physical association)	0.590
MALT1	MALT1	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (156): MALT1 (Affinity Capture-Western), MALT1 (Reconstituted Complex), UBE2V2 (Reconstituted Complex), UBE2N (Reconstituted Complex), MALT1 (Affinity Capture-MS), MALT1 (Affinity Capture-Western), CARD11 (Affinity Capture-Western), BCL10 (Affinity Capture-Western), IKBKG (Affinity Capture-Western), MAP3K7 (Affinity Capture-Western), TAB2 (Affinity Capture-Western), BCL10 (Affinity Capture-MS), TRAF6 (Affinity Capture-MS), MALT1 (Affinity Capture-Western), RBCK1 (Biochemical Activity)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A2AWP8, A2RRH5, C9J798, O43374, O70277, O95294, P04629, P59926, Q0GA42, Q13368, Q14318, Q16512, Q29RM4, Q2HY40, Q2T9P3, Q2TBA3, Q5BIM1, Q5M7W1, Q5R5M3, Q5R811, Q5T7P8, Q5XIS9, Q62746, Q6PFQ7, Q6PFY8, Q7TNM2, Q7TP90, Q7Z4K8, Q8BG60, Q8BHT7, Q8BQC3, Q8C6N3, Q8CIW5, Q8IZ69, Q8NCT1, Q920N2, Q92546, Q925B4

Diamond homologs: B0BNK7, B4MR28, D2HFT7, D4A1J9, D4ABX8, O60229, O60500, O97394, P0C5E3, P56974, Q08E66, Q14982, Q149C3, Q1RMS4, Q3UH53, Q3UQ28, Q3URE9, Q460M5, Q58EX2, Q5IS61, Q5STE3, Q60ZN5, Q62718, Q63HQ2, Q68FQ2, Q696W0, Q6NUX0, Q6PGX3, Q6PJG9, Q6UY18, Q6V4S5, Q7Z5N4, Q80TG9, Q80XU8, Q8AV57, Q8AV58, Q8BLY3, Q8BXA0, Q8N475, Q8WX93

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MALT1	up-regulates	TAB2	binding
TRAF6	up-regulates	MALT1	ubiquitination
CARD11	up-regulates	MALT1	binding
HECTD3	“up-regulates quantity by stabilization”	MALT1	polyubiquitination
MALT1	“form complex”	CBM	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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
Regulation of NF-kappa B signaling	6	90.6×	2e-09
TCR signaling	6	70.9×	9e-09
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	61.8×	5e-07
NOD1/2 Signaling Pathway	8	60.4×	8e-11
TNF signaling	6	60.4×	2e-08
activated TAK1 mediates p38 MAPK activation	5	59.1×	6e-07
TNFR1-induced NF-kappa-B signaling pathway	7	56.0×	2e-09
C-type lectin receptors (CLRs)	9	51.0×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	7	54.6×	7e-09
positive regulation of interleukin-2 production	5	49.8×	5e-06
obsolete positive regulation of NF-kappaB transcription factor activity	9	39.4×	3e-10
tumor necrosis factor-mediated signaling pathway	5	35.1×	2e-05
positive regulation of canonical NF-kappaB signal transduction	12	18.6×	3e-10
negative regulation of canonical NF-kappaB signal transduction	5	18.3×	3e-04
T cell receptor signaling pathway	5	16.1×	6e-04
defense response to bacterium	5	11.5×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	10
Uncertain significance	180
Likely benign	202
Benign	21

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1068658	NM_006785.4(MALT1):c.1356del (p.Glu453fs)	Pathogenic
127139	NM_006785.4(MALT1):c.1739G>C (p.Trp580Ser)	Pathogenic
1417195	NM_006785.4(MALT1):c.1318_1321del (p.Leu440fs)	Pathogenic
1454020	NM_006785.4(MALT1):c.818del (p.Lys273fs)	Pathogenic
1458444	NM_006785.4(MALT1):c.1661_1662insTTTTTTTTTTTTTTTTTNNNNNNNNNNGGCAGGGAGGTTGCAGTGAGCCGAGATGGCAGCAGTACAGTCCAGCTTCGGCTCCGCATGAGAGGGAGACCGTGGGGAGAGGGAGACAGAGCTCGAAGTAGTTT (p.Leu554delinsPhePhePhePhePhePheXaaXaaXaaXaaAlaGlyArgLeuGlnTer)	Pathogenic
1459602	NC_000018.9:g.(?56338876)(56339104_?)del	Pathogenic
2091535	NM_006785.4(MALT1):c.1504C>T (p.Gln502Ter)	Pathogenic
2571019	NM_006785.4(MALT1):c.1651C>T (p.Arg551Ter)	Pathogenic
2853331	NM_006785.4(MALT1):c.594del (p.Phe198fs)	Pathogenic
2863299	NM_006785.4(MALT1):c.1551_1554del (p.Arg518fs)	Pathogenic
3723656	NM_006785.4(MALT1):c.305_306del (p.Thr102fs)	Pathogenic
66089	NM_006785.4(MALT1):c.266G>T (p.Ser89Ile)	Pathogenic
662739	NM_006785.4(MALT1):c.611dup (p.Gln205fs)	Pathogenic
831577	NC_000018.10:g.(?58671624)(58747862_?)del	Pathogenic
935699	NM_006785.4(MALT1):c.1321del (p.Cys441fs)	Pathogenic
971304	NM_006785.4(MALT1):c.596_599dup (p.Phe200fs)	Pathogenic
1067741	NM_006785.4(MALT1):c.986-1G>C	Likely pathogenic
1331495	NM_006785.4(MALT1):c.1612_1615del (p.Lys538fs)	Likely pathogenic
1466078	NM_006785.4(MALT1):c.1475+1G>A	Likely pathogenic
1497535	NM_006785.4(MALT1):c.926-1G>A	Likely pathogenic
1526198	NM_006785.4(MALT1):c.1950del (p.Pro651fs)	Likely pathogenic
242617	NM_006785.3(MALT1):c.1019-2A>G	Likely pathogenic
2797070	NM_006785.4(MALT1):c.1911+1G>T	Likely pathogenic
3255329	NM_006785.4(MALT1):c.550G>T (p.Asp184Tyr)	Likely pathogenic
3583378	NM_006785.4(MALT1):c.886C>T (p.Arg296Ter)	Likely pathogenic
4735873	NM_006785.4(MALT1):c.949_958+73del	Likely pathogenic

SpliceAI

3305 predictions. Top by Δscore:

Variant	Effect	Δscore
18:58671853:G:A	donor_loss	1.0000
18:58681168:A:AG	acceptor_gain	1.0000
18:58681169:G:GA	acceptor_gain	1.0000
18:58681169:GT:G	acceptor_gain	1.0000
18:58681332:CCCAG:C	donor_loss	1.0000
18:58681333:CCAG:C	donor_loss	1.0000
18:58681334:CAG:C	donor_loss	1.0000
18:58681335:AG:A	donor_loss	1.0000
18:58681336:GGT:G	donor_loss	1.0000
18:58681337:G:GA	donor_loss	1.0000
18:58681338:T:G	donor_loss	1.0000
18:58696364:A:AG	acceptor_gain	1.0000
18:58696364:AG:A	acceptor_gain	1.0000
18:58696365:G:GA	acceptor_gain	1.0000
18:58696365:GG:G	acceptor_gain	1.0000
18:58696365:GGA:G	acceptor_gain	1.0000
18:58696485:G:GT	donor_gain	1.0000
18:58696485:GAG:G	donor_gain	1.0000
18:58696485:GAGG:G	donor_loss	1.0000
18:58696487:GGTAA:G	donor_loss	1.0000
18:58696488:G:A	donor_loss	1.0000
18:58696489:T:G	donor_loss	1.0000
18:58700587:CCAGA:C	donor_gain	1.0000
18:58700590:GA:G	donor_gain	1.0000
18:58700592:G:GG	donor_gain	1.0000
18:58700593:TA:T	donor_loss	1.0000
18:58700594:AA:A	donor_loss	1.0000
18:58710912:T:A	acceptor_gain	1.0000
18:58715932:T:G	acceptor_gain	1.0000
18:58723044:A:AG	acceptor_gain	1.0000

AlphaMissense

5423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:58696467:T:A	W160R	1.000
18:58696467:T:C	W160R	1.000
18:58696469:G:C	W160C	1.000
18:58696469:G:T	W160C	1.000
18:58700510:T:C	C190R	1.000
18:58700512:T:G	C190W	1.000
18:58700514:G:C	R191P	1.000
18:58700517:T:A	V192D	1.000
18:58700543:A:C	S201R	1.000
18:58700545:C:A	S201R	1.000
18:58700545:C:G	S201R	1.000
18:58723066:T:C	L346P	1.000
18:58733414:G:A	G414R	1.000
18:58733414:G:C	G414R	1.000
18:58733415:G:A	G414E	1.000
18:58733415:G:T	G414V	1.000
18:58733420:G:C	G416R	1.000
18:58733421:G:A	G416D	1.000
18:58733421:G:T	G416V	1.000
18:58733559:A:C	D462A	1.000
18:58733559:A:T	D462V	1.000
18:58733564:T:C	C464R	1.000
18:58733566:T:G	C464W	1.000
18:58733568:G:C	R465T	1.000
18:58733568:G:T	R465M	1.000
18:58733569:G:C	R465S	1.000
18:58733569:G:T	R465S	1.000
18:58734372:G:A	G489E	1.000
18:58734378:C:A	A491D	1.000
18:58735252:G:A	G509E	1.000

dbSNP variants (sampled 300 via entrez): RS1000021443 (18:58718776 A>G), RS1000033680 (18:58674499 G>C,T), RS1000093679 (18:58676704 A>G), RS1000120878 (18:58703673 G>C), RS1000122933 (18:58713830 T>C), RS1000208925 (18:58742145 C>T), RS1000231018 (18:58736755 G>C,T), RS1000265417 (18:58736483 C>G), RS1000290868 (18:58682131 T>G), RS1000331466 (18:58706420 T>C,G), RS1000350713 (18:58753502 C>T), RS1000354024 (18:58749200 A>G), RS1000354722 (18:58682855 G>A), RS1000380881 (18:58704427 T>A,C), RS1000424206 (18:58753938 T>C,G)

Disease associations

OMIM: gene MIM:604860 | disease phenotypes: MIM:615468

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency due to MALT1 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
combined immunodeficiency due to MALT1 deficiency	Definitive	AR

Mondo (2): combined immunodeficiency due to MALT1 deficiency (MONDO:0014197), severe combined immunodeficiency (MONDO:0015974)

Orphanet (2): Combined immunodeficiency due to MALT1 deficiency (Orphanet:397964), Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000265	Mastoiditis
HP:0000505	Visual impairment
HP:0000614	Abnormal nasolacrimal system morphology
HP:0000820	Abnormality of the thyroid gland
HP:0000939	Osteoporosis
HP:0000975	Hyperhidrosis
HP:0000988	Skin rash
HP:0001217	Clubbing
HP:0001510	Growth delay
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001945	Fever
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002043	Esophageal stricture
HP:0002110	Bronchiectasis
HP:0002113	Pulmonary infiltrates
HP:0002205	Recurrent respiratory infections
HP:0002716	Lymphadenopathy
HP:0002718	Recurrent bacterial infections
HP:0002721	Immunodeficiency
HP:0002750	Delayed skeletal maturation
HP:0002783	Recurrent lower respiratory tract infections
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004325	Decreased body weight
HP:0004429	Recurrent viral infections
HP:0011107	Recurrent aphthous stomatitis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001198_28	Multiple sclerosis	3.000000e-09
GCST009391_1619	Metabolite levels	2.000000e-06
GCST009597_331	Multiple sclerosis	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010379	phosphatidylcholine 36:1 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3632452 (SINGLE PROTEIN), CHEMBL3885522 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 32,903 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL395110	MEPAZINE	4	615
CHEMBL479	THIORIDAZINE	4	21,859
CHEMBL564	PROMAZINE	4	9,707
CHEMBL15192	LAPACHONE	2	589
CHEMBL5095244	SAFIMALTIB	2	133

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — C14: Caspase

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
SGR-1505	Inhibition	8.0	pIC50
JNJ-67856633	Inhibition	7.13	pIC50
safimaltib	Inhibition	7.13	pIC50
pecazine	Inhibition	6.29	pIC50
compound 20c [PMID: 34181850]	Inhibition	5.28	pIC50

Binding affinities (BindingDB)

238 measured of 388 human assays (455 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-1-(5-chloro-6- (difluoromethoxy) pyridin-3-yl)-3-(2- chloro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)urea	IC50	0.001 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- methoxypyridin-3- yl)-3-(2-chloro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-methyl 3-chloro- 5-(3-(2-chloro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)ureido)benzoate	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1- methylcyclopropyl)py- razolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1-methoxy- 2- methylpropyl)pyra- zolo[1,5-a]pyrimidin- 6-yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(2- (methoxymethyl)tetra- hydrofuran-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(6-(2H-1,2,3- triazol-2-yl)-5- (trifluoromethyl)pyri- din-3-yl)-3-(2-fluoro- 7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- fluoro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- methyl-7-(2- methyltetrahydrofuran- 2-yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	IC50	0.002 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(2- methoxypropan-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6- methoxypyridin-3- yl)-3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6-yl)-3- (3-cyano-4-(3- methyl-1H-1,2,4- triazol-1- yl)phenyl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(3-chloro-4-(2H- 1,2,3-triazol-2- yl)phenyl)-3-(2- chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6-yl)-3- (3,5-dichloro-4-(2H- 1,2,3-triazol-2- yl)phenyl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(7-(sec-butyl)-2- chloropyrazolo[1,5- a]pyrimidin-6-yl)-3- (5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1-(2- methoxyethoxy)ethyl) pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(R)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1- methoxypropan-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7- (methoxy(phenyl)meth- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- methyl-7-(1- methylcyclopropyl) pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(2-chloro-7-(1- methoxyethyl)pyrazo- lo[1,5-a]pyrimidin-6- yl)-3-(5- (difluoromethyl)-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (difluoromethoxy)py- ridin-3-yl)-3-(2- chloro-7-(1-(2- methoxyethoxy)ethyl) pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-((S)-1-(((S)- tetrahydrofuran-3- yl)methoxy)ethyl)pyra- zolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(R)-1-(6-(2H-1,2,3- triazol-2-yl)-5- (trifluoromethyl)pyri- din-3-yl)-3-(2-chloro- 7-(1- methoxypropan-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.003 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(2-chloro-7-(1-methoxyethyl)pyrazolo[1,5-a]pyrimidin-6-yl)-3-(2-(trifluoromethyl)pyridin-4-yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(4- methyl-2H-1,2,3- triazol-2-yl)pyridin-3- yl)-3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(4-(2- aminopyrimidin-4- yl)-3-chlorophenyl)- 3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(7-(tert-butyl)-2- chloropyrazolo[1,5- a]pyrimidin-6-yl)-3- (5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1- methoxypropan-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(2- methoxyphenyl)pyra- zolo[1,5-a]pyrimidin- 6-yl)urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-[2-chloro-7-(oxolan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	IC50	0.004 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(R)-1-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-3-(2-chloro-7-(1-methoxy-2-methylpropyl)pyrazolo[1,5-a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(2-chloro-7-(2- methoxypropan-2- yl)pyrazolo[1,5- a]pyrimidin-6-yl)-3- (2- (trifluoromethyl)pyridin- 4-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-1- methyl-6-oxo-2-(1H- pyrazol-1-yl)-1,6- dihydropyridin-3-yl)- 3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6- ethoxypyridin-3-yl)- 3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-bromopyridin-3- yl)-3-(2-chloro-7- isopropylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7- cyclobutylpyrazolo[1, 5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(4-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7- cyclopropylpyrazolo [1,5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(4- methyltetrahydro- 2H-pyran-4- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1,2- dimethoxyethyl)pyra- zolo[1,5-a]pyrimidin- 6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(5-chloro-6- (2H-1,2,3-triazol-2- yl)pyridin-3-yl)-3-(7- (1-methoxyethyl)-2- methylpyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(S)-1-(2-chloro-7-(1- methoxy-2- methylpropyl)pyra- zolo[1,5-a]pyrimidin- 6-yl)-3-(2- (trifluoromethyl)pyri- din-4-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-(1,2- dimethoxypropan-2- y)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-((S)-1-((R)- 2- methoxypropoxy)eth- yl)pyrazolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-((1R,2R)- 1,2- dimethoxypropyl)py- razolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-((S)-1-(((S)- tetrahydrofuran-3- yl)oxy)ethyl)pyrazolo [1,5-a]pyrimidin-6- yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
1-(5-chloro-6-(2H- 1,2,3-triazol-2- yl)pyridin-3-yl)-3-(2- chloro-7-((S)-1-(((R)- tetrahydrofuran-3- yl)methoxy)ethyl)pyra- zolo[1,5- a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors
(R)-1-(5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-3-(2-chloro-7-(1,2-dimethoxyethyl)pyrazolo[1,5-a]pyrimidin-6-yl)urea	IC50	0.005 nM	US-9815842: Pyrazolo pyrimidine derivatives and their use as MALT1 inhibitors

ChEMBL bioactivities

1212 potent at pChembl≥5 of 1287 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3806279
11.00	IC50	0.01	nM	CHEMBL6053196
11.00	IC50	0.01	nM	CHEMBL5918941
10.96	IC50	0.011	nM	CHEMBL5958499
10.96	IC50	0.011	nM	CHEMBL5745794
10.96	IC50	0.011	nM	CHEMBL5985777
10.96	IC50	0.011	nM	CHEMBL5978166
10.92	IC50	0.012	nM	CHEMBL5921519
10.92	IC50	0.012	nM	CHEMBL5837541
10.92	IC50	0.012	nM	CHEMBL5880742
10.89	IC50	0.013	nM	CHEMBL4787356
10.89	IC50	0.013	nM	CHEMBL5902912
10.89	IC50	0.013	nM	CHEMBL5821969
10.85	IC50	0.014	nM	CHEMBL5923187
10.85	IC50	0.014	nM	CHEMBL5859900
10.85	IC50	0.014	nM	CHEMBL5756085
10.85	IC50	0.014	nM	CHEMBL6046542
10.80	IC50	0.016	nM	CHEMBL5989735
10.74	IC50	0.018	nM	CHEMBL5977744
10.74	IC50	0.018	nM	CHEMBL5871497
10.72	IC50	0.019	nM	CHEMBL5974027
10.72	IC50	0.019	nM	CHEMBL6015225
10.72	IC50	0.019	nM	CHEMBL5971417
10.72	IC50	0.019	nM	CHEMBL4795308
10.72	IC50	0.019	nM	CHEMBL5852586
10.72	IC50	0.019	nM	CHEMBL5881012
10.72	IC50	0.019	nM	CHEMBL5807473
10.70	IC50	0.02	nM	CHEMBL5807334
10.70	IC50	0.02	nM	CHEMBL5741277
10.68	IC50	0.021	nM	CHEMBL5914076
10.68	IC50	0.021	nM	CHEMBL5772943
10.68	IC50	0.021	nM	CHEMBL6037936
10.68	IC50	0.021	nM	CHEMBL5785297
10.64	IC50	0.023	nM	CHEMBL3806155
10.62	IC50	0.024	nM	CHEMBL5922506
10.59	IC50	0.026	nM	CHEMBL5938299
10.55	IC50	0.028	nM	CHEMBL3805390
10.55	IC50	0.028	nM	CHEMBL5754450
10.54	IC50	0.029	nM	CHEMBL5995628
10.52	IC50	0.03	nM	CHEMBL5936437
10.52	IC50	0.03	nM	CHEMBL5996888
10.51	IC50	0.031	nM	CHEMBL3806155
10.47	IC50	0.034	nM	CHEMBL5846492
10.46	IC50	0.035	nM	CHEMBL5860799
10.41	IC50	0.039	nM	CHEMBL6013917
10.39	IC50	0.041	nM	CHEMBL5806906
10.38	IC50	0.042	nM	CHEMBL5955106
10.38	IC50	0.042	nM	CHEMBL5840365
10.35	IC50	0.045	nM	CHEMBL6037287
10.28	IC50	0.052	nM	CHEMBL3806279

PubChem BioAssay actives

426 with measured affinity, of 765 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-[4-[4-(aminomethyl)pyrazol-1-yl]-3-chlorophenyl]-3-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-[2-chloro-7-(oxolan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-[7-[(1S)-1-methoxyethyl]-2-methylpyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-(trifluoromethyl)-3-pyridinyl]urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)-3-[6-(1,1-dioxo-1,2-thiazolidin-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-[2-chloro-7-(1-cyclopropyl-2-methoxyethyl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1299812: Inhibition of MALT1 C domain (329 to 824 residues) (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg-Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence lifetime-based microtitre plate reader analysis	ic50	<0.0001	uM
1-(6-chloro-4-cyclopropylquinolin-3-yl)-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0020	uM
1-(5-chloro-6-methoxy-3-pyridinyl)-3-[6-cyano-4-[methyl(oxan-4-yl)amino]quinolin-3-yl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0020	uM
1-[2-chloro-7-(3,3-dimethylmorpholin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-(5-chloro-6-methoxy-3-pyridinyl)urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0020	uM
1-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0030	uM
1-[2-chloro-7-[(2R)-1-methoxypropan-2-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0030	uM
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0030	uM
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0040	uM
1-[2-chloro-7-[(2S)-1-methoxypropan-2-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0040	uM
1-(3-chloro-2-pyridinyl)-N-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]piperidine-4-carboxamide	1496189: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg’Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0040	uM
1-(2-chloro-7-cyclopropylpyrazolo[1,5-a]pyrimidin-6-yl)-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0050	uM
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(pyrrolidine-1-carbonyl)-3-pyridinyl]urea	1811030: Inhibition of MALT1 (329-824 residues) (unknown origin) using PT14 as substrate incubated for 60 mins by fluorescence based assay	ic50	0.0050	uM
1-(5-chloro-6-methoxy-3-pyridinyl)-3-[6-cyano-4-[(3S)-3-methylmorpholin-4-yl]quinolin-3-yl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0050	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-(4-cyclopropyl-6-fluoroquinolin-3-yl)urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0060	uM
1-[2-chloro-7-[(3S,5S)-3,5-dimethylmorpholin-4-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-(5-chloro-6-methoxy-3-pyridinyl)urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0060	uM
1-(3-chloro-4-methoxyphenyl)-3-[6-cyano-4-[(3S)-3-methylmorpholin-4-yl]quinolin-3-yl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0060	uM
1-[2-chloro-7-(3,3-dimethylmorpholin-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0060	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-[6-fluoro-4-(1-hydroxyethyl)quinolin-3-yl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0070	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-(4-cyclopropylquinolin-3-yl)urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0070	uM
1-(3-amino-2-pyridinyl)-N-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]piperidine-4-carboxamide	1496189: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg’Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0070	uM
1-(3-chloro-4-methoxyphenyl)-3-[6-cyano-4-[methyl(oxan-4-yl)amino]quinolin-3-yl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0080	uM
1-[2-chloro-7-[(3S,5S)-3,5-dimethylmorpholin-4-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0090	uM
(2R,4R)-1-(3-bromo-2-pyridinyl)-N-(3-chloro-4-methoxyphenyl)-2-methylpiperidine-4-carboxamide	1566347: Non-competitive inhibition of strep-tagged and His-tagged full length MALT1 protease (1 to 824 residues) (unknown origin) expressed in baculovirus infected insect cells assessed as inhibitory constant using AMC-coupled tetrapeptide LRSR as substrate incubated for 50 mins followed by substrate addition and measured after 4 hrs by fluorescence based assay	ki	0.0096	uM
1-[2-chloro-7-(oxan-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0100	uM
(2S)-1-[(2S)-2-[(4-bromobenzoyl)amino]-3-methylbutanoyl]-N-[(3S)-6-(diaminomethylideneamino)-1-fluoro-2-oxohexan-3-yl]pyrrolidine-2-carboxamide	1810957: Inhibition of MALT1 (340 to 789 residues) (unknown origin) using Ac-LRSR-AMC as substrate by fluorescence based analysis	ic50	0.0100	uM
1-[2-chloro-7-[(1R)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0130	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-(4-cyclopropyl-6-methoxyquinolin-3-yl)urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0130	uM
N-(5-chloro-6-methoxy-3-pyridinyl)-1-(3-chloro-2-pyridinyl)piperidine-4-carboxamide	1496189: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg’Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0130	uM
1-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)-3-[2-(trifluoromethyl)-4-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0150	uM
benzyl N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-[[6-(diaminomethylideneamino)-1-fluoro-2-oxohexan-3-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate	1575300: Inhibition of full-length human GST-tagged MALT1 isoform A (824 residues) expressed in Escherichia coli using Ac-LRSR-MCA as substrate after 1 hr by fluorescence assay	ic50	0.0160	uM
1-[2-bromo-7-[(3S)-3-methylmorpholin-4-yl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-(5-chloro-6-methoxy-3-pyridinyl)urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0170	uM
1-[2-chloro-7-(methoxymethyl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1701100: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg^Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0180	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-[6-fluoro-4-(1-methoxyethyl)quinolin-3-yl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0180	uM
1-(3-bromo-2-pyridinyl)-N-(3-chloro-4-methoxyphenyl)-2-methylpiperidine-4-carboxamide	1566351: Inhibition of MALT1-mediated T cell activation in human Jurkat cells assessed in decrease in PMA/ionomycin-induced IL2 production	ic50	0.0200	uM
N-(8-chloro-3-oxo-4H-1,4-benzoxazin-6-yl)-1-(3-chloro-2-pyridinyl)piperidine-4-carboxamide	1566338: Inhibition of strep-tagged and His-tagged full length MALT1 protease (1 to 824 residues) (unknown origin) expressed in baculovirus infected insect cells using AMC-coupled tetrapeptide LRSR as substrate incubated for 50 mins followed by substrate addition and measured after 4 hrs by fluorescence based assay	ic50	0.0200	uM
1-[[1,5-bis(4-chlorophenyl)pyrazol-3-yl]methyl]-2-[(3-chlorophenyl)methyl]-3-methylsulfonylguanidine	1940657: Inhibition of MALT1 (unknown origin)	ic50	0.0200	uM
N-[3-chloro-4-[3-(methylcarbamoyl)-1,2,4-triazol-1-yl]phenyl]-1-(3-chloro-2-pyridinyl)piperidine-4-carboxamide	1496189: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg’Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0210	uM
1-[(3R)-6-bromo-3,4-dihydro-2H-chromen-3-yl]-3-[3-chloro-4-(1,2,4-triazol-1-yl)phenyl]urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0260	uM
2-[[1,5-bis(4-chlorophenyl)pyrazol-3-yl]methyl]-1-methylsulfonyl-3-(thiophen-2-ylmethyl)guanidine	1940657: Inhibition of MALT1 (unknown origin)	ic50	0.0260	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-[4-(1-ethoxyethyl)-6-fluoroquinolin-3-yl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0270	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-[4-(1-hydroxyethyl)quinolin-3-yl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0280	uM
N-(3-chloro-4-fluorophenyl)-1-(3-chloro-2-pyridinyl)piperidine-4-carboxamide	1496189: Inhibition of MALT1 (unknown origin) using Ac-Trp-Leu-Arg-Ser-Arg’Cys(PT14)-NH2 as substrate preincubated for 60 mins followed by substrate addition measured after 60 mins by fluorescence assay	ic50	0.0280	uM
1-(6-bromo-4-chloroquinolin-3-yl)-3-(3-chloro-4-methoxyphenyl)urea	1683594: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay	ic50	0.0290	uM
1-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]-3-[7-(1-methoxyethyl)-2-methyl-[1,3]thiazolo[5,4-b]pyridin-6-yl]urea	1673253: Inhibition of MALT1 (unknown origin) by Glosensor reporter gene assay	ic50	0.0300	uM
1-(3-bromo-2-pyridinyl)-N-(5-chloro-6-methoxy-3-pyridinyl)piperidine-4-carboxamide	1566338: Inhibition of strep-tagged and His-tagged full length MALT1 protease (1 to 824 residues) (unknown origin) expressed in baculovirus infected insect cells using AMC-coupled tetrapeptide LRSR as substrate incubated for 50 mins followed by substrate addition and measured after 4 hrs by fluorescence based assay	ic50	0.0300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Arsenic	affects cotreatment, increases abundance, affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Fluorouracil	increases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	decreases expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2-anisidine	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases activity	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1

ChEMBL screening assays

130 unique, capped per target: 128 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3635348	Binding	Inhibition of MALT1 in human Jurkat cell lysate preincubated for 2 hrs followed by addition of 25 uM Ac-LRSR-AMC substrate for 3 hrs by fluorescence based assay	Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma. — J Med Chem
CHEMBL5210029	Functional	Affinity Phenotypic Cellular interaction (Jurkat IL-2 (IL2-RGA PMA + anti-CD28)) EUB0000239b MALT1	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WE	Abcam HeLa MALT1 KO	Cancer cell line	Female
CVCL_B8JY	Abcam HCT 116 MALT1 KO	Cancer cell line	Male
CVCL_B8YF	Abcam MCF-7 MALT1 KO	Cancer cell line	Female
CVCL_B9M7	Abcam A-549 MALT1 KO	Cancer cell line	Male
CVCL_D7U0	Ubigene A-549 MALT1 KO	Cancer cell line	Male
CVCL_D8PP	Ubigene HCT 116 MALT1 KO	Cancer cell line	Male
CVCL_D9J1	Ubigene HEK293 MALT1 KO	Transformed cell line	Female
CVCL_E0GX	Ubigene HeLa MALT1 KO	Cancer cell line	Female
CVCL_E2BT	HAP1 MALT1 (-)	Cancer cell line	Male
CVCL_ZE82	BMA19	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts