MALT1

Chr 18AR

MALT1 paracaspase

Also known as: IMD12, MLT, MLT1, PCASP1

NCBI Gene: 10892ENSG00000172175UniProt: Q9UDY8

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Immunodeficiency 12MIM #615468
AR
2
Active trials
58
Pubs (1 yr)
24
P/LP submissions
5%
P/LP missense
0.30
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— MALT1
🧬
Gene-Disease Validity (ClinGen)
combined immunodeficiency due to MALT1 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 83 VUS of 300 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.987
Z-score 4.94
OE 0.15 (0.08–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.84Z-score
OE missense 0.59 (0.53–0.66)
229 obs / 385.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.08–0.30)
0≤0.351.4
Missense OE0.59 (0.53–0.66)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 6 / 39.5Missense obs/exp: 229 / 385.9Syn Z: 1.35

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic6
VUS83
Likely Benign169
Benign12
15
Pathogenic
6
Likely Pathogenic
83
VUS
169
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
12
0
15
Likely Pathogenic
2
1
3
0
6
VUS
1
77
5
0
83
Likely Benign
0
0
77
92
169
Benign
0
0
12
0
12
Total67810992285

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MALT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Therapeutic targeting of MALT1 in oncology: Mechanism, inhibitor development, and clinical prospects.
Cao X et al.·J Cell Commun Signal
2026Open AccessFunctional
Novel Compounds as MALT1 Inhibitors for Treating Cancer.
Sabnis RW.·ACS Med Chem Lett
2026
MALT1 Knockdown Alleviates Multiorgan Injury and Inflammation Through Inhibiting TAK1/NF-κB Signaling Pathway-Mediated T-Helper 1 and 17 Differentiations in LPS-induced Inflammation.
Huang Q et al.·Inflammation
2026Open Access
Decoding Allosteric Inhibition in MALT1: The Hidden Role of Conformational Plasticity in Metastable States via Biased MD and Deep Learning.
Santos RM et al.·J Phys Chem B
2026Open Access
Succinate-mediated activation of the GPR91/MALT1/NF-κB/CCL2 pathway in macrophages contributes to pulmonary fibrosis.
Zhang X et al.·Int Immunopharmacol
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients