MALT1
MALT1 Paracaspase: A Key Regulator of NF-κB Signaling and Immune Homeostasis
Gene Information Card
| Symbol | MALT1 |
|---|---|
| Full Name | MALT1 paracaspase |
| Gene Type | Protein coding |
| Chromosomal Location | 18q21.32 |
| NCBI Gene ID | 10892 ncbi.nlm.nih.gov/gene/10892 |
| Ensembl ID | ENSG00000172156 |
| UniProt ID | Q9UDY8 |
| OMIM ID | 604860 |
| HGNC ID | 6819 |
| Aliases | MLT, IMD12, paracaspase, PCASP1 |
Description
The MALT1 gene encodes a paracaspase protein that functions as a key scaffold and protease in the CARD11-BCL10-MALT1 (CBM) complex, essential for NF-κB activation downstream of antigen receptors in lymphocytes. MALT1 mediates both T cell and B cell activation, proliferation, and survival. Mutations in MALT1 are associated with combined immunodeficiency (IMD12) and are recurrently implicated in B-cell lymphomas, particularly MALT lymphoma, through chromosomal translocations and gain-of-function alterations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucosa-associated lymphoid tissue (MALT) lymphoma | Chromosomal translocations (e.g., t(11;18)(q21;q21) involving BIRC3) lead to constitutive NF-κB activation via MALT1 paracaspase activity. | COSMIC, OMIM #604860 |
| Combined immunodeficiency (IMD12) | Loss-of-function mutations impair CBM complex assembly and NF-κB signaling, resulting in defective T and B cell responses. | ClinVar, OMIM #615468 |
| Diffuse large B-cell lymphoma (DLBCL) | Gain-of-function mutations in MALT1 (e.g., R149W) enhance paracaspase activity and promote NF-κB-driven lymphomagenesis. | COSMIC, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 32.5 | High |
| Spleen | 28.1 | High |
| Bone marrow | 18.7 | Medium |
| Lung | 8.3 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (Burkitt lymphoma) | 45.2 | B-cell line, high expression |
| Jurkat (T-cell leukemia) | 38.9 | T-cell line, high expression |
| HEK293 (embryonic kidney) | 12.4 | Non-immune cell line, moderate expression |
| K562 (chronic myeloid leukemia) | 6.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R149W | Missense | 0.5% in DLBCL | Gain-of-function; enhances paracaspase activity and NF-κB signaling |
| c.1690C>T (p.R564*) | Nonsense | Rare in IMD12 | Loss-of-function; truncation, impaired CBM complex |
| t(11;18)(q21;q21) BIRC3-MALT1 | Chromosomal translocation | ~50% of MALT lymphoma | Fusion protein with constitutive paracaspase activity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) in MALT1 impair CBM complex formation and NF-κB activation, leading to combined immunodeficiency (IMD12) with defective T and B cell responses.
Gain of Function (GOF)
Gain-of-function mutations (e.g., R149W) increase paracaspase activity, enhancing NF-κB signaling and promoting lymphomagenesis, particularly in DLBCL and MALT lymphoma.
Dominant Negative (DN)
Dominant-negative effects have been reported for certain MALT1 mutations that disrupt CBM complex assembly without complete loss of protein, leading to partial NF-κB inhibition and immune dysregulation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-kappaB signaling pathway (KEGG hsa04064)
• T cell receptor signaling pathway (KEGG hsa04660)
• B cell receptor signaling pathway (KEGG hsa04662)
• CBM complex signaling (Reactome R-HSA-445989)
Protein Summary
MALT1 (paracaspase) is a 824-amino acid protein containing an N-terminal death domain, three immunoglobulin-like domains, and a C-terminal caspase-like domain with proteolytic activity. It functions as a scaffold and protease within the CBM complex, cleaving substrates such as A20, CYLD, and BCL10 to positively regulate NF-κB signaling. MALT1 is essential for lymphocyte activation and immune responses. Its dysregulation through mutations or translocations contributes to immunodeficiency and lymphoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MALT1 Knockout HEK293 Cell Line | EDJ-KQ576 | Human | 10892 | Details Get a Quote |
| MALT1 Knockout A-549 Cell Line | EDJ-KQ18972 | Human | 10892 | Details Get a Quote |
| MALT1 Knockout HCT 116 Cell Line | EDJ-KQ18973 | Human | 10892 | Details Get a Quote |
| MALT1 Knockout HeLa Cell Line | EDJ-KQ18974 | Human | 10892 | Details Get a Quote |
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