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 (9 variants)
• not provided (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				94	2	96
missense			153	4	2	159
nonsense	2	1	1			4
start loss						0
frameshift	8	3	2			13
inframe indel			6			6
splice donor/acceptor (+/-2bp)		4				4
splice region			8	19	8	35
non coding			2	53	7	62
Total	10	8	164	151	11

Highest pathogenic variant AF is 0.00000657

Variants in MALT1

This is a list of pathogenic ClinVar variants found in the MALT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-58671560-G-A		not specified	Benign (Mar 29, 2016)
18-58671609-G-A		not specified	Uncertain significance (Mar 29, 2016)
18-58671652-G-T		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Jan 31, 2024)
18-58671666-T-C		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Aug 04, 2022)
18-58671668-C-G		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Dec 23, 2021)
18-58671669-A-G		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Aug 15, 2020)
18-58671671-G-A		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Aug 31, 2021)
18-58671673-C-T			Likely benign (Jun 01, 2022)
18-58671679-G-T		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Jan 21, 2021)
18-58671681-C-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (May 26, 2021)
18-58671684-C-G		Combined immunodeficiency due to MALT1 deficiency • Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
18-58671684-C-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Jul 14, 2022)
18-58671685-G-A		Combined immunodeficiency due to MALT1 deficiency • MALT1-related disorder	Likely benign (Oct 05, 2022)
18-58671685-G-C		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Feb 04, 2022)
18-58671688-C-T		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Nov 01, 2022)
18-58671692-C-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Feb 03, 2022)
18-58671696-C-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Oct 26, 2019)
18-58671697-G-C		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Jan 22, 2024)
18-58671699-G-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (May 08, 2023)
18-58671703-G-A		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Jun 10, 2021)
18-58671706-G-C		Combined immunodeficiency due to MALT1 deficiency	Likely benign (May 15, 2020)
18-58671710-G-A		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Jan 21, 2023)
18-58671714-C-T		Combined immunodeficiency due to MALT1 deficiency	Uncertain significance (Mar 26, 2021)
18-58671718-G-A		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Dec 27, 2022)
18-58671721-C-T		Combined immunodeficiency due to MALT1 deficiency	Likely benign (Jan 29, 2024)

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