MALT1

MALT1 paracaspase, the group of Immunoglobulin like domain containing|CBM complex

Basic information

Region (hg38): 18:58671465-58754477

Previous symbols: [ "MLT" ]

Links

ENSG00000172175

∙ NCBI:10892 ∙ OMIM:604860 ∙ HGNC:6819 ∙ Uniprot:Q9UDY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined immunodeficiency due to MALT1 deficiency (Moderate), mode of inheritance: AR
combined immunodeficiency due to MALT1 deficiency (Strong), mode of inheritance: AR
combined immunodeficiency due to MALT1 deficiency (Supportive), mode of inheritance: AR
combined immunodeficiency due to MALT1 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 12	AR	Allergy/Immunology/Infectious	Individuals have been described as suffering from primary immunodeficiency including infantile-onset recurrent bacterial and candidal infections, and awareness may allow prophylaxis and early and aggressive treatment of infections	Allergy/Immunology/Infectious	23727036; 24332264

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MALT1 gene.

Combined_immunodeficiency_due_to_MALT1_deficiency (396 variants)
Inborn_genetic_diseases (56 variants)
not_provided (33 variants)
MALT1-related_disorder (9 variants)
not_specified (2 variants)
Severe_combined_immunodeficiency_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MALT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006785.4. Only rare variants are included in the table.

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

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

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				109 clinvar	3 clinvar	112
missense	2 clinvar	1 clinvar	173 clinvar	6 clinvar	1 clinvar	183
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss						0
frameshift	10 clinvar	3 clinvar	3 clinvar			16
splice donor/acceptor (+/-2bp)		5 clinvar				5
Total	15	11	177	115	4

Highest pathogenic variant AF is 0.000015162773

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MALT1	protein_coding	protein_coding	ENST00000348428	17	78754

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0135	125727	0	18	125745	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.84	229	386	0.593	0.0000185	5400
Missense in Polyphen		49	155.79	0.31453		2121
Synonymous	1.35	118	138	0.854	0.00000670	1549
Loss of Function	4.94	6	39.5	0.152	0.00000203	533

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000244	0.000243
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000991	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000329	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Enhances BCL10-induced activation of NF-kappa-B. Involved in nuclear export of BCL10. Binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity. Has ubiquitin ligase activity. 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 (By similarity). {ECO:0000250|UniProtKB:Q2TBA3, ECO:0000269|PubMed:11262391, ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:18264101}.;
Disease: DISEASE: Note=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. {ECO:0000269|PubMed:10339464, ECO:0000269|PubMed:10523859, ECO:0000269|PubMed:10702396, ECO:0000269|PubMed:11090634}.;
Pathway: T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);B Cell Receptor Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;T-Cell antigen Receptor (TCR) Signaling Pathway;B cell receptor signaling;Downstream TCR signaling;TCR signaling;Activation of NF-kappaB in B cells;Signaling by the B Cell Receptor (BCR);CLEC7A/inflammasome pathway;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);BCR;BCR signaling pathway;FCERI mediated NF-kB activation;Canonical NF-kappaB pathway;TCR signaling in naïve CD8+ T cells;TCR signaling in naïve CD4+ T cells;CD4 T cell receptor signaling-NFkB cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

pRec: 0.166

Intolerance Scores

loftool: 0.492
rvis_EVS: -0.14
rvis_percentile_EVS: 43.77

Haploinsufficiency Scores

pHI: 0.142
hipred: Y
hipred_score: 0.853
ghis: 0.598

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.627

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Malt1
Phenotype: hematopoietic system phenotype; immune system phenotype;

Gene ontology

Biological process: B-1 B cell differentiation;stimulatory C-type lectin receptor signaling pathway;positive regulation of T cell cytokine production;proteolysis;defense response;activation of NF-kappaB-inducing kinase activity;response to fungus;protein ubiquitination;positive regulation of protein ubiquitination;lipopolysaccharide-mediated signaling pathway;positive regulation of interleukin-2 production;Fc-epsilon receptor signaling pathway;T cell proliferation;B cell activation;regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;T cell receptor signaling pathway;regulation of T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;nuclear export;protein complex oligomerization;positive regulation of T-helper 17 cell differentiation
Cellular component: fibrillar center;nucleus;nucleolus;cytoplasm;cytosol;CBM complex;protein-containing complex;perinuclear region of cytoplasm
Molecular function: protease binding;cysteine-type endopeptidase activity;ubiquitin-protein transferase activity;protein binding;peptidase activity;kinase activator activity;identical protein binding;protein self-association