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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NLRP4
NLR family pyrin domain containing 4
Chromosome 19 · 19q13.43
NCBI Gene: 147945Ensembl: ENSG00000160505.16HGNC: HGNC:22943UniProt: B2RCA1
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
molecular adaptor activitynegative regulation of innate immune responsecytoplasmregulation of inflammatory responsemacular degenerationRespiratory insufficiencydiabetic ketoacidosisneoplasm
✦AI Summary

NLRP4 is a member of the nucleotide-binding and leucine-rich repeat (NLR) family that functions as a multifaceted regulator of immune and cellular processes. NLRP4 serves as a negative regulator of autophagy by directly interacting with Beclin1, an essential autophagy regulator, through its NACHT domain 1. The protein also associates with the class C vacuolar protein-sorting complex to negatively regulate autophagosome maturation 1. In xenophagy, NLRP4 acts as a pattern recognition sensor that binds ARHGDIA to regulate Rho GTPase signaling and facilitate actin-mediated formation of autophagosome-like vacuoles for bacterial elimination 2. NLRP4 negatively regulates type I interferon responses through the cGAS-STING-IRF3/IRF7 pathway 3. The protein shows clinical significance in cancer contexts: elevated NLRP4 expression correlates with olaparib resistance in pancreatic cancer by enhancing DNA repair capacity and promoting ROS-induced autophagy 4, while NLRP4 mutations in non-small-cell lung cancer patients are associated with improved responses to anti-PD-1 therapy and longer progression-free survival 3. Additionally, NLRP4 upregulation characterizes macrophage activation syndrome in adult-onset Still's disease 5.

Sources cited
1
NLRP4 negatively regulates autophagy by interacting with Beclin1 and the class C vacuolar protein-sorting complex
PMID: 21209283
2
NLRP4 functions as a pattern recognition sensor that regulates Rho GTPase signaling for xenophagy
PMID: 29099277
3
NLRP4 negatively regulates type I interferon responses and mutations correlate with improved anti-PD-1 therapy outcomes
PMID: 34927309
4
NLRP4 promotes olaparib resistance in pancreatic cancer through DNA repair enhancement and autophagy induction
PMID: 39187531
5
NLRP4 hyperexpression characterizes macrophage activation syndrome in adult-onset Still's disease
PMID: 35467709
Disease Associationsⓘ20
macular degenerationOpen Targets
0.27Weak
Respiratory insufficiencyOpen Targets
0.27Weak
diabetic ketoacidosisOpen Targets
0.10Weak
neoplasmOpen Targets
0.09Suggestive
Down syndromeOpen Targets
0.06Suggestive
colorectal adenocarcinomaOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
adult-onset Still's diseaseOpen Targets
0.02Suggestive
diffuse large B-cell lymphomaOpen Targets
0.02Suggestive
Crohn's diseaseOpen Targets
0.02Suggestive
macrophage activation syndromeOpen Targets
0.01Suggestive
Carcinoma, Lewis LungOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
central nervous system cancerOpen Targets
0.01Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
bacterial diseaseOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DTX4Protein interaction100%NLRP7Protein interaction91%BECN1Protein interaction89%TBK1Protein interaction85%CASP1Protein interaction77%MEFVProtein interaction77%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
0%
Lung
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
NLRP4DTX4NLRP7BECN1TBK1CASP1MEFV
PROTEIN STRUCTURE
Preparing viewer…
PDB4EWI · 2.28 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.65LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.50 [0.39–0.65]
RankingsWhere NLRP4 stands among ~20K protein-coding genes
  • #11,756of 20,598
    Most Researched31
  • #4,642of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedNLRP4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NLRP4 renders pancreatic cancer resistant to olaparib through promotion of the DNA damage response and ROS-induced autophagy.
PMID: 39187531
Cell Death Dis · 2024
1.00
2
Characterization of inflammasome-related genes in urine sediments of patients receiving intravesical BCG therapy.
PMID: 28888400
Urol Oncol · 2017
0.90
3
Structural and functional analysis of the NLRP4 pyrin domain.
PMID: 22928810
Biochemistry · 2012
0.80
4
Epigenetic Mechanisms of Inflammasome Regulation.
PMID: 32796686
Int J Mol Sci · 2020
0.70
5
NLRP4 negatively regulates autophagic processes through an association with beclin1.
PMID: 21209283
J Immunol · 2011
0.60