Summary of NLRP3
The gene codes for a protein, NLR family pyrin domain containing 3. Mutations are linked to familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID) [R].
The Function of NLRP3
As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, beta-amyloid fibers, environmental or industrial particles and nanoparticles, etc. However, it is unclear what constitutes the direct NLRP3 activator. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF.
Protein names
Recommended name:
NACHT, LRR and PYD domains-containing protein 3Short name:
CLR1.1Alternative name(s):
Angiotensin/vasopressin receptor AII/AVP-likeCaterpiller protein 1.1
Cold-induced autoinflammatory syndrome 1 protein
Cryopyrin
PYRIN-containing APAF1-like protein 1
- RS10157379 (NLRP3) ??
- RS10754558 (NLRP3) ??
- RS10925015 (NLRP3) ??
- RS12239046 (NLRP3) ??
- RS1539019 (NLRP3) ??
- RS35829419 (NLRP3) ??
- RS3806268 (NLRP3) ??
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Top Gene-Substance Interactions
NLRP3 Interacts with These Diseases
| Disease | Score |
Substances That Increase NLRP3
| Substances | Interaction | Organism | Category |
Substances That Decrease NLRP3
| Substances | Interaction | Organism | Category |
Advanced Summary
familial cold autoinflammatory syndrome Several mutations in the NLRP3 gene have been identified in people with familial cold autoinflammatory syndrome. These mutations are in a region of the gene known as exon 3. Researchers believe that the mutations cause cryopyrin to be hyperactive, leading to episodes of fever and inflammation that are usually triggered by exposure to cold. Muckle-Wells syndrome At least 10 mutations in exon 3 of the NLRP3 gene have been identified in people with Muckle-Wells syndrome. These mutations are believed to cause hyperactive cryopyrin, resulting in episodes of fever and inflammation, as well as the hearing loss and kidney problems that occur in Muckle-Wells syndrome. neonatal onset multisystem inflammatory disease About 30 mutations in the NLRP3 gene have been identified in people with neonatal onset multisystem inflammatory disease (NOMID). Almost all of these mutations are found in exon 3. The mutations likely cause cryopyrin to be hyperactive, leading to an inappropriate inflammatory response that results in episodes of fever and widespread inflammatory damage to the body's cells and tissues. It is unclear why some mutations in exon 3 cause the severe symptoms of NOMID, some cause the less serious familial cold autoinflammatory syndrome, and others cause Muckle-Wells syndrome, which is intermediate in severity.
The NLRP3 gene (also known as CIAS1) provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins, which are found in the fluid inside cells (cytoplasm). Cryopyrin is found mainly in white blood cells and in cartilage-forming cells (chondrocytes). NLR proteins are involved in the immune system, helping to start and regulate the immune system's response to injury, toxins, or invasion by microorganisms. These proteins recognize specific molecules, become activated, and respond by helping to engage components of the immune system. Cryopyrin recognizes bacterial particles; chemicals such as asbestos, silica, and uric acid crystals; and compounds released by injured cells. Once activated, groups of cryopyrin molecules assemble themselves along with other proteins into structures called inflammasomes, which are involved in the process of inflammation. Inflammation occurs when the immune system sends signaling molecules as well as white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Predominantly expressed in macrophages. Also expressed in dendritic cells, B- and T-cells (at protein level) (PubMed:11786556) (PubMed:17164409). Expressed in LPS-treated granulocytes, but not in resting cells (at protein level) (PubMed:17164409). Expression in monocytes is very weak (at protein level) (PubMed:17164409). Expressed in stratified non-keratinizing squamous epithelium, including oral, esophageal and ectocervical mucosa and in the Hassall's corpuscles in the thymus. Also, detected in the stratified epithelium covering the bladder and ureter (transitional mucosa) (at protein level) (PubMed:17164409). Expressed in chondrocytes (PubMed:12032915). Expressed at low levels in resting osteoblasts (PubMed:17907925).
Gene Pathways:
Induction:
By activators of Toll-like receptors, such as lipoteichoic acid (LTA) (TLR2), polyinosine-polycytidylic acid (poly(I:C), a synthetic analog of dsRNA) (TLR3) and bacterial lipopolysaccharides (LPS) (TLR4), and by TNF (PubMed:14662828). Up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level) (PubMed:17907925).
Molecular Function:
Biological Processes:
- Activation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Apoptotic Process
- Cellular Response To Lipopolysaccharide
- Defense Response
- Defense Response To Virus
- Detection Of Biotic Stimulus
- Inflammatory Response
- Innate Immune Response
- Interleukin-18 Production
- Interleukin-1 Beta Production
- Interleukin-1 Secretion
- Negative Regulation Of Acute Inflammatory Response
- Negative Regulation Of Inflammatory Response
- Negative Regulation Of Interleukin-1 Beta Secretion
- Negative Regulation Of Nf-Kappab Import Into Nucleus
- Negative Regulation Of Nf-Kappab Transcription Factor Activity
- Nlrp3 Inflammasome Complex Assembly
- Positive Regulation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Positive Regulation Of Interleukin-13 Production
- Positive Regulation Of Interleukin-1 Beta Secretion
- Positive Regulation Of Interleukin-4 Production
- Positive Regulation Of Interleukin-5 Production
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of T-Helper 17 Cell Differentiation
- Positive Regulation Of T-Helper 2 Cell Cytokine Production
- Positive Regulation Of T-Helper 2 Cell Differentiation
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Type 2 Immune Response
- Protein Oligomerization
- Signal Transduction
- Transcription, Dna-Templated