MALT1

Chr 18AR

MALT1 paracaspase

Also known as: IMD12, MLT, MLT1, PCASP1

NCBI Gene: 10892 ENSG00000172175 UniProt: Q9UDY8 OMIM: 604860

This gene encodes a caspase-like protease that forms CBM signaling complexes to activate NF-κB and p38 MAP kinase pathways, promoting expression of pro-inflammatory cytokines and mediating T-cell receptor signaling and lymphocyte activation. Mutations cause immunodeficiency 12, an autosomal recessive primary immunodeficiency affecting adaptive and innate immune responses. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.3), indicating that biallelic mutations causing severe protein disruption are likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, May 2018]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 12MIM #615468

Clinical highlights

Gene-disease validity (ClinGen)

combined immunodeficiency due to MALT1 deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

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Mechanism