NLRP3

NLR family pyrin domain containing 3, the group of NLR family|Pyrin domain containing

Basic information

Region (hg38): 1:247416155-247449108

Previous symbols: [ "C1orf7", "CIAS1", "DFNA34" ]

Links

ENSG00000162711 ∙ NCBI:114548 ∙ OMIM:606416 ∙ HGNC:16400 ∙ Uniprot:Q96P20 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• CINCA syndrome (Strong), mode of inheritance: AD
• keratitis fugax hereditaria (Limited), mode of inheritance: AD
• Muckle-Wells syndrome (Supportive), mode of inheritance: AD
• CINCA syndrome (Supportive), mode of inheritance: AD
• familial cold autoinflammatory syndrome (Supportive), mode of inheritance: AD
• CINCA syndrome (Definitive), mode of inheritance: AD
• familial cold autoinflammatory syndrome 1 (Strong), mode of inheritance: AD
• cryopyrin-associated periodic syndrome (Definitive), mode of inheritance: AD
• CINCA syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chronic Infantile Neurologic Cutaneous Articular (CINCA) syndrome; Deafness, autosomal dominant, 34, with or without inflammation; Muckle-Wells syndrome; Neonatal Onset Multisystem Inflammatory Disease (NOMID); Familial cold-induced autoinflammatory syndrome 1	AD	Allergy/Immunology/Infectious	Individuals may present with autoinflammatory manifestions, which can be severe, progressive, and ultimately fatal, medical treatment with IL1R antagonists (eg, anakinra, canakinumab) has been described as an effective treatment; In Familial cold-induced autoinflammatory syndrome 1, medical management (eg, with stanozolol) has been described as beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dermatologic; Ophthalmologic; Renal	14476827; 5769632; 5173311; 49161; 447320; 8447672; 11687797; 12032915; 12483741; 11992256; 12928894; 16532456; 21356079; 21538043; 21859692; 21967869; 22193915; 22723549; 28847925; 29366613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLRP3 gene.

• Cryopyrin associated periodic syndrome (592 variants)
• not provided (261 variants)
• Familial cold autoinflammatory syndrome 1 (173 variants)
• not specified (102 variants)
• Familial amyloid nephropathy with urticaria AND deafness (100 variants)
• Chronic infantile neurological, cutaneous and articular syndrome (98 variants)
• Autoinflammatory syndrome (73 variants)
• Inborn genetic diseases (21 variants)
• NLRP3-related condition (12 variants)
• Lung adenocarcinoma (8 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome (8 variants)
• Familial cold autoinflammatory syndrome (6 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1 (5 variants)
• Hearing loss, autosomal dominant 34, with or without inflammation (5 variants)
• Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation (4 variants)
• Keratitis fugax hereditaria (4 variants)
• Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome (4 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome (4 variants)
• Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation (3 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria (3 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation (3 variants)
• Kidney disorder (3 variants)
• Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria (3 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria (3 variants)
• Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1 (2 variants)
• Focal segmental glomerulosclerosis (2 variants)
• Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1 (2 variants)
• Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1 (2 variants)
• Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation (2 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria (2 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1 (1 variants)
• Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria (1 variants)
• Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Keratitis fugax hereditaria;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 (1 variants)
• Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1 (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1 (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Squamous cell carcinoma (1 variants)
• Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Familial cold autoinflammatory syndrome 1 (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome (1 variants)
• Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1 (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1 (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Keratitis fugax hereditaria;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1 (1 variants)
• Keratitis fugax hereditaria;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Inflammatory abnormality of the skin (1 variants)
• Familial cold autoinflammatory syndrome 1;Chronic infantile neurological, cutaneous and articular syndrome;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• NLRP3-related disorder (1 variants)
• Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome (1 variants)
• Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness (1 variants)
• Hearing impairment (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation;Keratitis fugax hereditaria (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1 (1 variants)
• Hearing loss, autosomal dominant 34, with or without inflammation;Familial amyloid nephropathy with urticaria AND deafness;Chronic infantile neurological, cutaneous and articular syndrome;Familial cold autoinflammatory syndrome 1;Keratitis fugax hereditaria (1 variants)
• Atypical hemolytic-uremic syndrome (1 variants)
• Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial amyloid nephropathy with urticaria AND deafness;Familial cold autoinflammatory syndrome 1;Hearing loss, autosomal dominant 34, with or without inflammation (1 variants)
• Familial amyloid nephropathy with urticaria AND deafness;Hearing loss, autosomal dominant 34, with or without inflammation;Chronic infantile neurological, cutaneous and articular syndrome;Keratitis fugax hereditaria;Familial cold autoinflammatory syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRP3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	176	15	204
missense	19	27	323	6		375
nonsense	1		11			12
start loss						0
frameshift			4			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)			3			3
splice region			10	15	1	26
non coding			28	37	56	121
Total	20	27	384	219	71

Highest pathogenic variant AF is 0.00000657

Variants in NLRP3

This is a list of pathogenic ClinVar variants found in the NLRP3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-247417746-A-G		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
1-247418091-C-T		Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
1-247418115-C-T		Familial cold autoinflammatory syndrome 1 • Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome	Uncertain significance (Jan 13, 2018)
1-247418116-G-A		Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
1-247418172-C-T		Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
1-247418240-T-G		Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1	Benign (Jan 13, 2018)
1-247418258-A-T		Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome	Benign (Jan 13, 2018)
1-247418268-C-G		Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome 1	Uncertain significance (Jan 12, 2018)
1-247418268-C-T		Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome 1	Benign (Jan 12, 2018)
1-247418278-G-A		Familial cold autoinflammatory syndrome 1 • Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome	Uncertain significance (Jan 12, 2018)
1-247418307-C-CT		Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome • Familial amyloid nephropathy with urticaria AND deafness	Uncertain significance (Jun 14, 2016)
1-247418341-G-A		Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome	Uncertain significance (Jan 13, 2018)
1-247418390-T-C		Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness	Benign (Jan 13, 2018)
1-247418394-C-T		Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness	Uncertain significance (Jan 12, 2018)
1-247418432-G-A		Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1	Uncertain significance (Jan 13, 2018)
1-247418462-C-T		Chronic infantile neurological, cutaneous and articular syndrome • Familial cold autoinflammatory syndrome 1 • Familial amyloid nephropathy with urticaria AND deafness	Uncertain significance (Jan 12, 2018)
1-247418570-G-A		Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1	Benign (Jan 13, 2018)
1-247418582-G-A		Familial amyloid nephropathy with urticaria AND deafness • Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome	Uncertain significance (Jan 13, 2018)
1-247418598-G-A		Familial cold autoinflammatory syndrome 1 • Familial amyloid nephropathy with urticaria AND deafness • Chronic infantile neurological, cutaneous and articular syndrome	Uncertain significance (Jan 12, 2018)
1-247418655-T-C		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
1-247418679-T-C		Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness	Conflicting classifications of pathogenicity (Jan 01, 2023)
1-247418680-T-C		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
1-247418722-C-T			Benign (Mar 03, 2015)
1-247418727-G-A		Familial cold autoinflammatory syndrome 1 • Chronic infantile neurological, cutaneous and articular syndrome • Familial amyloid nephropathy with urticaria AND deafness	Uncertain significance (Jan 13, 2018)
1-247418729-G-A		not specified	Uncertain significance (Dec 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLRP3	protein_coding	protein_coding	ENST00000336119	9	32953

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000811	0.999	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.14	414	556	0.744	0.0000333	6854
Missense in Polyphen		123	206.94	0.59436		2670
Synonymous	-3.41	301	235	1.28	0.0000153	1958
Loss of Function	3.94	13	39.8	0.326	0.00000226	483

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000869	0.0000869
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000109
Finnish	0.000416	0.000416
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000163	0.000109
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. 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:0000305|PubMed:23305783}.
• Disease: 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 mutations 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 mutations 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 mutations 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 mutations affecting the gene represented in this entry.
• Pathway: Pertussis - Homo sapiens (human);Influenza A - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Nucleotide-binding Oligomerization Domain (NOD) pathway;IL1 and megakaryocytes in obesity;The NLRP3 inflammasome;Inflammasomes;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Metalloprotease DUBs;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.00351
• rvis_EVS: -0.95
• rvis_percentile_EVS: 9.38

Haploinsufficiency Scores

• pHI: 0.417
• hipred: Y
• hipred_score: 0.655
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.848

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nlrp3
• Phenotype: hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; liver/biliary system phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: cytokine secretion involved in immune response;negative regulation of acute inflammatory response;positive regulation of type 2 immune response;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;defense response;inflammatory response;signal transduction;detection of biotic stimulus;protein deubiquitination;negative regulation of NF-kappaB transcription factor activity;interleukin-1 beta production;interleukin-18 production;positive regulation of interleukin-13 production;positive regulation of interleukin-4 production;positive regulation of interleukin-5 production;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;NLRP3 inflammasome complex assembly;innate immune response;positive regulation of T-helper 2 cell differentiation;positive regulation of transcription by RNA polymerase II;interleukin-1 secretion;negative regulation of interleukin-1 beta secretion;positive regulation of interleukin-1 beta secretion;negative regulation of inflammatory response;defense response to Gram-positive bacterium;positive regulation of NF-kappaB transcription factor activity;protein complex oligomerization;defense response to virus;cellular response to lipopolysaccharide;cellular response to peptidoglycan;negative regulation of NIK/NF-kappaB signaling;positive regulation of T-helper 17 cell differentiation;positive regulation of T-helper 2 cell cytokine production
• Cellular component: extracellular region;nucleus;cytoplasm;endoplasmic reticulum;cytosol;NLRP3 inflammasome complex
• Molecular function: protein binding;ATP binding;transcription factor binding;identical protein binding;peptidoglycan binding;sequence-specific DNA binding