UniProt functional annotation for Q96P20



	UniProt functional annotation for Q96P20

UniProt code: Q96P20.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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 (PubMed:28847925). 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, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209). 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 (By similarity). {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:28847925, ECO:0000305|PubMed:23305783}.

Subunit: Sensor component of NLRP3 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1 and, possibly, CASP4 and CASP5). Within the complex, NLRP3 and PYCARD interact via their respective DAPIN/pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process (PubMed:24630722). NLRP3 localizes at the end of each PYCARD filament (PubMed:24630722). Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization (PubMed:24630722). CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. Reconstituted ternary inflammasomes show star-shaped structures, in which multiple filaments, containing CASP1, protrude radially from a single central hub, containing the sensor protein and PYCARD (PubMed:24630722). In this complex, the sensor protein is sub- stoichiometric to PYCARD, and PYCARD is further substoichiometric to CASP1, suggesting amplifications of signal transduction from the sensor, via the adapter, to the effector (PubMed:24630722). Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422) (PubMed:26347139). Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli (PubMed:22801494). Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (PubMed:23430110). Directly interacts with IRF4 (via the LRR domain); this interaction is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (By similarity). Interacts (via NACHT domain) with DHX33 (via DEAH box) (PubMed:23871209). Interacts with PYDC5 (PubMed:24531343). Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (By similarity) Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs) (PubMed:23809162). Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome (PubMed:24517500). {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:17431422, ECO:0000269|PubMed:21880711, ECO:0000269|PubMed:22461501, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23430110, ECO:0000269|PubMed:23809162, ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:24517500, ECO:0000269|PubMed:24531343, ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:26347139, ECO:0000305|PubMed:23305783, ECO:0000305|PubMed:25354325}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:14662828, ECO:0000269|PubMed:17164409}. Inflammasome {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:14662828, ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:23871209}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q8R4B8}. Secreted {ECO:0000269|PubMed:24952504}. Nucleus {ECO:0000250|UniProtKB:Q8R4B8}. Note=In macrophages, under resting conditions, mainly located in the cytosol, on the endoplasmic reticulum. After stimulation with inducers of the NLRP3 inflammasome, mitochondria redistribute in the vicinity of the endoplasmic reticulum in the perinuclear region, which results in colocalization of NLRP3 on the endoplasmic reticulum and PYCARD on mitochondria, allowing the activation of inflammasome assembly. After the induction of pyroptosis, inflammasome specks are released into the extracellular space where they can further promote IL1B processing and where they can be engulfed by macrophages. Phagocytosis induces lysosomal damage and inflammasome activation in the recipient cells (PubMed:24952504). In the Th2 subset of CD4(+) helper T-cells, mainly located in the nucleus. Nuclear localization depends upon KPNA2. In the Th1 subset of CD4(+) helper T-cells, mainly cytoplasmic (By similarity). {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:24952504}.

Subcellular location: Golgi apparatus membrane. Note=(Microbial infection) Upon HRSV infection, the protein is mainly located in lipid rafts in the Golgi membrane. {ECO:0000269|PubMed:23229815}.

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 lung epithelial cells (at protein level) (PubMed:23229815). Expressed in chondrocytes (PubMed:12032915). Expressed at low levels in resting osteoblasts (PubMed:17907925). {ECO:0000269|PubMed:11786556, ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:17164409, ECO:0000269|PubMed:17907925, ECO:0000269|PubMed:23229815}.

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). In macrophages, up-regulated by endocannabinoid anandamide/AEA (PubMed:23955712). {ECO:0000269|PubMed:14662828, ECO:0000269|PubMed:17907925, ECO:0000269|PubMed:23955712}.

Domain: The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD-binding. {ECO:0000269|PubMed:24630722}.

Domain: The LRR domain mediates the interaction with IRF4 and PML. {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:23430110}.

Domain: Intramolecular interactions between NACHT and leucine-rich repeat (LRR) domains may be important for autoinhibition in the absence of activating signal. {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000305|PubMed:11786556}.

Ptm: The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation. {ECO:0000305|PubMed:21880711}.

Ptm: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ubiquitination does not lead to degradation, but inhibits inflammasome activation (By similarity). Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly. This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP. {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:22948162}.

Disease: Familial cold autoinflammatory syndrome 1 (FCAS1) [MIM:120100]: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:12522564, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:17284928, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Muckle-Wells syndrome (MWS) [MIM:191900]: A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Chronic infantile neurologic cutaneous and articular syndrome (CINCA) [MIM:607115]: Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. {ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:12483741, ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15231984, ECO:0000269|PubMed:15334500, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Keratoendothelitis fugax hereditaria (KEFH) [MIM:148200]: An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. {ECO:0000269|PubMed:29366613}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Deafness, autosomal dominant, 34, with or without inflammation (DFNA34) [MIM:617772]: A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. {ECO:0000269|PubMed:28847925}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the NLRP family. {ECO:0000305}.

Sequence caution: Sequence=AAC39910.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL12497.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL12498.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL33908.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL65136.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD92128.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG37494.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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 (PubMed:28847925). 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, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209). 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 (By similarity). {ECO:0000250\|UniProtKB:Q8R4B8, ECO:0000269\|PubMed:22801494, ECO:0000269\|PubMed:23871209, ECO:0000269\|PubMed:28847925, ECO:0000305\|PubMed:23305783}.


Subunit:		Sensor component of NLRP3 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1 and, possibly, CASP4 and CASP5). Within the complex, NLRP3 and PYCARD interact via their respective DAPIN/pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process (PubMed:24630722). NLRP3 localizes at the end of each PYCARD filament (PubMed:24630722). Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization (PubMed:24630722). CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. Reconstituted ternary inflammasomes show star-shaped structures, in which multiple filaments, containing CASP1, protrude radially from a single central hub, containing the sensor protein and PYCARD (PubMed:24630722). In this complex, the sensor protein is sub- stoichiometric to PYCARD, and PYCARD is further substoichiometric to CASP1, suggesting amplifications of signal transduction from the sensor, via the adapter, to the effector (PubMed:24630722). Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422) (PubMed:26347139). Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli (PubMed:22801494). Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (PubMed:23430110). Directly interacts with IRF4 (via the LRR domain); this interaction is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (By similarity). Interacts (via NACHT domain) with DHX33 (via DEAH box) (PubMed:23871209). Interacts with PYDC5 (PubMed:24531343). Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (By similarity) Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs) (PubMed:23809162). Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome (PubMed:24517500). {ECO:0000250\|UniProtKB:Q8R4B8, ECO:0000269\|PubMed:11786556, ECO:0000269\|PubMed:15030775, ECO:0000269\|PubMed:17431422, ECO:0000269\|PubMed:21880711, ECO:0000269\|PubMed:22461501, ECO:0000269\|PubMed:22801494, ECO:0000269\|PubMed:23430110, ECO:0000269\|PubMed:23809162, ECO:0000269\|PubMed:23871209, ECO:0000269\|PubMed:24517500, ECO:0000269\|PubMed:24531343, ECO:0000269\|PubMed:24630722, ECO:0000269\|PubMed:26347139, ECO:0000305\|PubMed:23305783, ECO:0000305\|PubMed:25354325}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:11786556, ECO:0000269\|PubMed:14662828, ECO:0000269\|PubMed:17164409}. Inflammasome {ECO:0000269\|PubMed:11786556, ECO:0000269\|PubMed:14662828, ECO:0000269\|PubMed:17164409, ECO:0000269\|PubMed:23871209}. Endoplasmic reticulum {ECO:0000250\|UniProtKB:Q8R4B8}. Secreted {ECO:0000269\|PubMed:24952504}. Nucleus {ECO:0000250\|UniProtKB:Q8R4B8}. Note=In macrophages, under resting conditions, mainly located in the cytosol, on the endoplasmic reticulum. After stimulation with inducers of the NLRP3 inflammasome, mitochondria redistribute in the vicinity of the endoplasmic reticulum in the perinuclear region, which results in colocalization of NLRP3 on the endoplasmic reticulum and PYCARD on mitochondria, allowing the activation of inflammasome assembly. After the induction of pyroptosis, inflammasome specks are released into the extracellular space where they can further promote IL1B processing and where they can be engulfed by macrophages. Phagocytosis induces lysosomal damage and inflammasome activation in the recipient cells (PubMed:24952504). In the Th2 subset of CD4(+) helper T-cells, mainly located in the nucleus. Nuclear localization depends upon KPNA2. In the Th1 subset of CD4(+) helper T-cells, mainly cytoplasmic (By similarity). {ECO:0000250\|UniProtKB:Q8R4B8, ECO:0000269\|PubMed:24952504}.
Subcellular location:		Golgi apparatus membrane. Note=(Microbial infection) Upon HRSV infection, the protein is mainly located in lipid rafts in the Golgi membrane. {ECO:0000269\|PubMed:23229815}.
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 lung epithelial cells (at protein level) (PubMed:23229815). Expressed in chondrocytes (PubMed:12032915). Expressed at low levels in resting osteoblasts (PubMed:17907925). {ECO:0000269\|PubMed:11786556, ECO:0000269\|PubMed:12032915, ECO:0000269\|PubMed:17164409, ECO:0000269\|PubMed:17907925, ECO:0000269\|PubMed:23229815}.
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). In macrophages, up-regulated by endocannabinoid anandamide/AEA (PubMed:23955712). {ECO:0000269\|PubMed:14662828, ECO:0000269\|PubMed:17907925, ECO:0000269\|PubMed:23955712}.
Domain:		The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD-binding. {ECO:0000269\|PubMed:24630722}.
Domain:		The LRR domain mediates the interaction with IRF4 and PML. {ECO:0000250\|UniProtKB:Q8R4B8, ECO:0000269\|PubMed:23430110}.
Domain:		Intramolecular interactions between NACHT and leucine-rich repeat (LRR) domains may be important for autoinhibition in the absence of activating signal. {ECO:0000250\|UniProtKB:Q9EPB4, ECO:0000305\|PubMed:11786556}.
Ptm:		The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation. {ECO:0000305\|PubMed:21880711}.
Ptm:		Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ubiquitination does not lead to degradation, but inhibits inflammasome activation (By similarity). Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly. This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP. {ECO:0000250\|UniProtKB:Q8R4B8, ECO:0000269\|PubMed:22948162}.
Disease:		Familial cold autoinflammatory syndrome 1 (FCAS1) [MIM:120100]: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. {ECO:0000269\|PubMed:11687797, ECO:0000269\|PubMed:11992256, ECO:0000269\|PubMed:12355493, ECO:0000269\|PubMed:12522564, ECO:0000269\|PubMed:15593220, ECO:0000269\|PubMed:17284928, ECO:0000269\|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Muckle-Wells syndrome (MWS) [MIM:191900]: A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. {ECO:0000269\|PubMed:11687797, ECO:0000269\|PubMed:11992256, ECO:0000269\|PubMed:12355493, ECO:0000269\|PubMed:15593220, ECO:0000269\|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Chronic infantile neurologic cutaneous and articular syndrome (CINCA) [MIM:607115]: Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. {ECO:0000269\|PubMed:12032915, ECO:0000269\|PubMed:12483741, ECO:0000269\|PubMed:14630794, ECO:0000269\|PubMed:15231984, ECO:0000269\|PubMed:15334500, ECO:0000269\|PubMed:15593220, ECO:0000269\|PubMed:24952504}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Keratoendothelitis fugax hereditaria (KEFH) [MIM:148200]: An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. {ECO:0000269\|PubMed:29366613}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Deafness, autosomal dominant, 34, with or without inflammation (DFNA34) [MIM:617772]: A form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. {ECO:0000269\|PubMed:28847925}. Note=The disease may be caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the NLRP family. {ECO:0000305}.
Sequence caution:		Sequence=AAC39910.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL12497.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL12498.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL33908.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL65136.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAD92128.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAG37494.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};