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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NLRP3
NLR family pyrin domain containing 3
Chromosome 1 Β· 1q44
NCBI Gene: 114548Ensembl: ENSG00000162711.19HGNC: HGNC:16400UniProt: A0A7I2PJH0
1,292PubMed Papers
25Diseases
0Drugs
64Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
molecular condensate scaffold activityATP bindingATP hydrolysis activityprotein-macromolecule adaptor activityCINCA syndromeMuckle-Wells syndromefamilial cold autoinflammatory syndrome 1keratitis fugax hereditaria
✦AI Summary

NLRP3 (NLR family pyrin domain containing 3) is a cytosolic pattern recognition receptor that forms the NLRP3 inflammasome, a multiprotein complex crucial for innate immune responses. The primary function of NLRP3 is to activate caspase-1, leading to maturation of pro-inflammatory cytokines IL-1Ξ² and IL-18 and induction of pyroptosis 12. The NLRP3 inflammasome can be activated by diverse stimuli through a common mechanism involving disassembly of the trans-Golgi network (TGN), where NLRP3 is recruited to dispersed TGN via ionic bonding with phosphatidylinositol-4-phosphate, serving as a scaffold for NLRP3 aggregation and ASC polymerization 3. Activation is regulated by multiple post-translational modifications, including palmitoylation at Cys126 by ZDHHC7 4 and SUMOylation by TRIM28, which stabilizes NLRP3 protein levels 5. Mitochondrial dysfunction positively regulates NLRP3 activation through ROS generation, while autophagy and mitophagy negatively regulate the inflammasome 67. Dysregulation of NLRP3 is associated with various autoinflammatory diseases and has been linked to M1 macrophage polarization in inflammatory conditions 8, making it a promising therapeutic target for inflammatory disorders 1.

Sources cited
1
NLRP3 inflammasome triggers caspase activation and IL-1Ξ² maturation, linked to autoinflammatory diseases
PMID: 26549800
2
NLRP3 inflammasome activates caspase-1, leading to IL-1Ξ²/IL-18 maturation and pyroptosis
PMID: 27669650
3
NLRP3 activation involves recruitment to dispersed trans-Golgi network via PtdIns4P binding
PMID: 30487600
4
NLRP3 Cys126 palmitoylation by ZDHHC7 promotes inflammasome activation
PMID: 38583156
5
TRIM28 SUMOylates NLRP3, stabilizing protein levels and facilitating inflammasome activation
PMID: 34373456
6
Mitochondrial dysfunction and ROS generation positively regulate NLRP3 activation
PMID: 21124315
7
Autophagy and mitophagy negatively regulate NLRP3 inflammasome activation
PMID: 39417249
8
NLRP3 inflammasome mediates M1 macrophage polarization and IL-1Ξ² production
PMID: 31976565
Disease Associationsβ“˜25
CINCA syndromeOpen Targets
0.84Strong
Muckle-Wells syndromeOpen Targets
0.80Strong
familial cold autoinflammatory syndrome 1Open Targets
0.80Strong
keratitis fugax hereditariaOpen Targets
0.69Moderate
Familial cold urticariaOpen Targets
0.69Moderate
autosomal dominant nonsyndromic hearing lossOpen Targets
0.67Moderate
cryopyrin-associated periodic syndromeOpen Targets
0.58Moderate
autoinflammatory syndromeOpen Targets
0.52Moderate
severe acute respiratory syndromeOpen Targets
0.47Moderate
familial cold autoinflammatory syndromeOpen Targets
0.41Moderate
COVID-19Open Targets
0.40Weak
genetic disorderOpen Targets
0.34Weak
Cerebral arteriovenous malformationOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.31Weak
FeverOpen Targets
0.26Weak
Pleural effusionOpen Targets
0.26Weak
pericardial effusionOpen Targets
0.26Weak
response to antihypertensive drugOpen Targets
0.26Weak
Tietze syndromeOpen Targets
0.26Weak
Ischemic strokeOpen Targets
0.23Weak
Chronic infantile neurologic cutaneous and articular syndromeUniProt
Deafness, autosomal dominant, 34, with or without inflammationUniProt
Familial cold autoinflammatory syndrome 1UniProt
Keratoendothelitis fugax hereditariaUniProt
Muckle-Wells syndromeUniProt
Pathogenic Variants64
NM_001243133.2(NLRP3):c.1058T>C (p.Leu353Pro)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|not specified|Cryopyrin associated periodic syndrome|Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria|NLRP3-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 353
NM_001243133.2(NLRP3):c.1043C>T (p.Thr348Met)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Familial amyloid nephropathy with urticaria AND deafness|Cryopyrin associated periodic syndrome|Autoinflammatory syndrome|Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness
β˜…β˜…β˜†β˜†2025β†’ Residue 348
NM_001243133.2(NLRP3):c.1316C>T (p.Ala439Val)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome|Autoinflammatory syndrome|Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria
β˜…β˜…β˜†β˜†2025β†’ Residue 439
NM_001243133.2(NLRP3):c.1699G>A (p.Glu567Lys)Pathogenic
Familial cold autoinflammatory syndrome 1|Cryopyrin associated periodic syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 567
NM_001243133.2(NLRP3):c.902G>A (p.Gly301Asp)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 301
NM_001243133.2(NLRP3):c.778C>T (p.Arg260Ter)Pathogenic
Familial amyloid nephropathy with urticaria AND deafness|Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome|Autoinflammatory syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 260
NM_001243133.2(NLRP3):c.778_780delinsTGG (p.Arg260Trp)Pathogenic
not provided|Chronic infantile neurological, cutaneous and articular syndrome|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 260
NM_001243133.2(NLRP3):c.907G>A (p.Asp303Asn)Pathogenic
Familial amyloid nephropathy with urticaria AND deafness|Chronic infantile neurological, cutaneous and articular syndrome|Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 303
NM_001243133.2(NLRP3):c.1307C>T (p.Thr436Ile)Pathogenic
Familial cold autoinflammatory syndrome 1|Cryopyrin associated periodic syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 436
NM_001243133.2(NLRP3):c.2575T>C (p.Tyr859His)Pathogenic
not provided|Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria|Cryopyrin associated periodic syndrome|NLRP3-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 859
NM_001243133.2(NLRP3):c.2576A>G (p.Tyr859Cys)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria|Familial amyloid nephropathy with urticaria AND deafness
β˜…β˜…β˜†β˜†2024β†’ Residue 859
NM_001243133.2(NLRP3):c.931G>A (p.Glu311Lys)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Familial amyloid nephropathy with urticaria AND deafness|Cryopyrin associated periodic syndrome|Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria
β˜…β˜…β˜†β˜†2024β†’ Residue 311
NM_001243133.2(NLRP3):c.1315G>A (p.Ala439Thr)Pathogenic
Familial cold autoinflammatory syndrome 1|Cryopyrin associated periodic syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 439
NM_001243133.2(NLRP3):c.1217T>C (p.Met406Thr)Pathogenic
Cryopyrin associated periodic syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 406
NM_001243133.2(NLRP3):c.1054G>A (p.Ala352Thr)Likely pathogenic
Familial cold autoinflammatory syndrome 1|Cryopyrin associated periodic syndrome|Chronic infantile neurological, cutaneous and articular syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 352
NM_001243133.2(NLRP3):c.910G>A (p.Glu304Lys)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2022β†’ Residue 304
NM_001243133.2(NLRP3):c.1213A>C (p.Thr405Pro)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 405
NM_001243133.2(NLRP3):c.914T>C (p.Leu305Pro)Pathogenic
Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome|Autoinflammatory syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 305
NM_001243133.2(NLRP3):c.1055C>T (p.Ala352Val)Pathogenic
Familial amyloid nephropathy with urticaria AND deafness|Familial cold autoinflammatory syndrome 1|not provided|Cryopyrin associated periodic syndrome
β˜…β˜…β˜†β˜†2020β†’ Residue 352
NM_001243133.2(NLRP3):c.1695A>C (p.Lys565Asn)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 565
View on ClinVar β†—
Related Genes
RELAProtein interaction100%DDX3XProtein interaction100%DHX33Protein interaction100%MAVSProtein interaction100%CASP5Protein interaction100%IFI16Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
6%
Brain
2%
Heart
1%
Liver
1%
Ovary
1%
Gene Interaction Network
Click a node to explore
NLRP3RELADDX3XDHX33MAVSCASP5IFI16
PROTEIN STRUCTURE
Preparing viewer…
PDB3QF2 Β· 1.70 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.64LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.50 [0.40–0.64]
RankingsWhere NLRP3 stands among ~20K protein-coding genes
  • #108of 20,598
    Most Researched1,292 Β· top 1%
  • #1,114of 5,498
    Most Pathogenic Variants64 Β· top quartile
  • #4,557of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedNLRP3
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Molecular mechanisms regulating NLRP3 inflammasome activation.
PMID: 26549800
Cell Mol Immunol Β· 2016
1.00
2
Mechanism and Regulation of NLRP3 Inflammasome Activation.
PMID: 27669650
Trends Biochem Sci Β· 2016
0.90
3
STAT3 promotes NLRP3 inflammasome activation by mediating NLRP3 mitochondrial translocation.
PMID: 39218978
Exp Mol Med Β· 2024
0.82
4
A role for mitochondria in NLRP3 inflammasome activation.
PMID: 21124315
Nature Β· 2011
0.80
5
The Role of the NLRP3 Inflammasome and Programmed Cell Death in Acute Liver Injury.
PMID: 36834481
Int J Mol Sci Β· 2023
0.78