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NLRP3 NLR family pyrin domain containing 3 [ Homo sapiens (human) ]

Gene ID: 114548, updated on 5-Apr-2020

Summary

Official Symbol
NLRP3provided by HGNC
Official Full Name
NLR family pyrin domain containing 3provided by HGNC
Primary source
HGNC:HGNC:16400
See related
Ensembl:ENSG00000162711 MIM:606416
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AII; AVP; FCU; MWS; FCAS; KEFH; CIAS1; FCAS1; NALP3; C1orf7; CLR1.1; DFNA34; PYPAF1; AGTAVPRL
Summary
This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Oct 2008]
Expression
Biased expression in bone marrow (RPKM 20.0), appendix (RPKM 6.0) and 9 other tissues See more
Orthologs

Genomic context

See NLRP3 in Genome Data Viewer
Location:
1q44
Exon count:
11
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (247416163..247448823)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (247579247..247612410)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene zinc finger protein 496 Neighboring gene translation initiation factor IF-2-like Neighboring gene Sharpr-MPRA regulatory region 5917 Neighboring gene uncharacterized LOC107985375 Neighboring gene olfactory receptor family 2 subfamily B member 11 Neighboring gene olfactory receptor family 2 subfamily W member 5 (gene/pseudogene)

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Chronic infantile neurological, cutaneous and articular syndrome
MedGen: C0409818 OMIM: 607115 GeneReviews: Not available
Compare labs
DEAFNESS, AUTOSOMAL DOMINANT 34, WITH OR WITHOUT INFLAMMATION
MedGen: C4521680 OMIM: 617772 GeneReviews: Not available
Compare labs
Familial amyloid nephropathy with urticaria AND deafness
MedGen: C0268390 OMIM: 191900 GeneReviews: Not available
Compare labs
Familial cold urticaria
MedGen: C4551895 OMIM: 120100 GeneReviews: Not available
Compare labs
Keratitis fugax hereditaria
MedGen: C1835697 OMIM: 148200 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study for reading and language abilities in two population cohorts.
NHGRI GWA Catalog
Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.
NHGRI GWA Catalog
Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.
NHGRI GWA Catalog
Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope transmembrane glycoprotein gp41 env HIV-1 inhibitors T20, NVP, AZT, and raltegravir significantly attenuate HIV-1-induced IL-1B production and NLRP3 activation, suggesting that HIV-1 gp41, RT, and IN are required for pro-IL-1B expression and NLRP3 activation PubMed
integrase gag-pol HIV-1 inhibitors T20, NVP, AZT, and raltegravir significantly attenuate HIV-1-induced IL-1B production and NLRP3 activation, suggesting that HIV-1 gp41, RT, and IN are required for pro-IL-1B expression and NLRP3 activation PubMed
reverse transcriptase gag-pol HIV-1 inhibitors T20, NVP, AZT, and raltegravir significantly attenuate HIV-1-induced IL-1B production and NLRP3 activation, suggesting that HIV-1 gp41, RT, and IN are required for pro-IL-1B expression and NLRP3 activation PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ95925

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
peptidoglycan binding TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
transcription factor binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
NLRP3 inflammasome complex assembly IEA
Inferred from Electronic Annotation
more info
 
activation of cysteine-type endopeptidase activity involved in apoptotic process IEA
Inferred from Electronic Annotation
more info
 
apoptotic process NAS
Non-traceable Author Statement
more info
PubMed 
cellular response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to lipopolysaccharide IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to peptidoglycan IEA
Inferred from Electronic Annotation
more info
 
cytokine secretion involved in immune response IEA
Inferred from Electronic Annotation
more info
 
defense response TAS
Traceable Author Statement
more info
PubMed 
defense response to Gram-positive bacterium IEA
Inferred from Electronic Annotation
more info
 
defense response to virus IEA
Inferred from Electronic Annotation
more info
 
detection of biotic stimulus TAS
Traceable Author Statement
more info
PubMed 
inflammatory response IMP
Inferred from Mutant Phenotype
more info
PubMed 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
interleukin-1 beta production IEA
Inferred from Electronic Annotation
more info
 
interleukin-1 secretion IEA
Inferred from Electronic Annotation
more info
 
interleukin-18 production IEA
Inferred from Electronic Annotation
more info
 
negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of NIK/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of NIK/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of acute inflammatory response IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of inflammatory response IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of interleukin-1 beta secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IPI
Inferred from Physical Interaction
more info
PubMed 
positive regulation of T-helper 17 cell differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T-helper 2 cell cytokine production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of T-helper 2 cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-1 beta secretion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of interleukin-1 beta secretion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-1 beta secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of interleukin-13 production IEA
Inferred from Electronic Annotation
more info
 
positive regulation of interleukin-4 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-5 production IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of type 2 immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
protein deubiquitination TAS
Traceable Author Statement
more info
 
signal transduction NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
Golgi membrane IDA
Inferred from Direct Assay
more info
PubMed 
NLRP3 inflammasome complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
extracellular region IEA
Inferred from Electronic Annotation
more info
 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 

General protein information

Preferred Names
NACHT, LRR and PYD domains-containing protein 3
Names
NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3
NACHT, LRR and PYD containing protein 3
PYRIN-containing APAF1-like protein 1
caterpiller protein 1.1
cold autoinflammatory syndrome 1 protein
cold-induced autoinflammatory syndrome 1 protein
cryopyrin
cryopyrin, NACHT, LRR and PYD domains - containing protein 3
deafness, autosomal dominant 34
nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007509.2 RefSeqGene

    Range
    4984..37936
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_197

mRNA and Protein(s)

  1. NM_001079821.3NP_001073289.2  NACHT, LRR and PYD domains-containing protein 3 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 6. Both variants 3 and 6 encode the same isoform (e).
    Source sequence(s)
    AC104335, AF410477, AK314998, AL606804
    Related
    ENSP00000375704.3, ENST00000391828.7
  2. NM_001127461.3NP_001120933.2  NACHT, LRR and PYD domains-containing protein 3 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 6. The encoded isoform (c) is shorter than isoform e.
    Source sequence(s)
    AB208891, AC104335, AK314998
    Consensus CDS
    CCDS44346.1
    Related
    ENSP00000355453.2, ENST00000366497.6
  3. NM_001127462.3NP_001120934.2  NACHT, LRR and PYD domains-containing protein 3 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate in-frame exon in the mid-coding region, compared to variant 6. The encoded isoform (d) is shorter than isoform e.
    Source sequence(s)
    AC104335, AF410477, AL606804, AY422168
    Consensus CDS
    CCDS44347.1
    Related
    ENSP00000375703.2, ENST00000391827.2
  4. NM_001243133.2NP_001230062.1  NACHT, LRR and PYD domains-containing protein 3 isoform e

    See identical proteins and their annotated locations for NP_001230062.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) represents the longest transcript and encodes isoform e. Variants 1 and 6 represent the same transcript but use different translation start sites since both sites are likely used. The encoded isoform (e) uses the most conserved translation start site. Both variants 3 and 6 encode the same isoform (e).
    Source sequence(s)
    AC104335, AF410477, AF427617
    UniProtKB/Swiss-Prot
    Q96P20
    Conserved Domains (5) summary
    cd00116
    Location:573949
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:891
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:741769
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:218387
    NACHT; NACHT domain
    pfam14484
    Location:142207
    FISNA; Fish-specific NACHT associated domain
  5. NM_004895.5NP_004886.3  NACHT, LRR and PYD domains-containing protein 3 isoform a

    See identical proteins and their annotated locations for NP_004886.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the same transcript, but uses an upstream translation start codon, compared to variant 6. Variants 1 and 6 represent the same transcript but use different translation start sites since both sites are likely used. The encoded isoform (a) uses a less conserved upstream translation start codon and has a slightly longer N-terminus, compared to isoform e.
    Source sequence(s)
    AC104335, AF410477, AF427617
    Consensus CDS
    CCDS1632.1
    UniProtKB/Swiss-Prot
    Q96P20
    Related
    ENSP00000337383.3, ENST00000336119.7
    Conserved Domains (5) summary
    cd00116
    Location:575951
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
  6. NM_183395.3NP_899632.2  NACHT, LRR and PYD domains-containing protein 3 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks two alternate in-frame exons, which are located in the mid-coding and 3' coding regions, compared to variant 6. The encoded isoform (b) is shorter than isoform e.
    Source sequence(s)
    AC104335, AF410477, AF427617, AL606804, AY092033
    Consensus CDS
    CCDS1633.1
    Related
    ENSP00000294752.3, ENST00000348069.6

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    247416163..247448823
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017000182.1XP_016855671.1  NACHT, LRR and PYD domains-containing protein 3 isoform X1

    UniProtKB/Swiss-Prot
    Q96P20
    Conserved Domains (5) summary
    cd00116
    Location:575951
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
  2. XM_017000181.1XP_016855670.1  NACHT, LRR and PYD domains-containing protein 3 isoform X1

    UniProtKB/Swiss-Prot
    Q96P20
    Conserved Domains (5) summary
    cd00116
    Location:575951
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
  3. XM_011544048.2XP_011542350.1  NACHT, LRR and PYD domains-containing protein 3 isoform X1

    See identical proteins and their annotated locations for XP_011542350.1

    UniProtKB/Swiss-Prot
    Q96P20
    Conserved Domains (5) summary
    cd00116
    Location:575951
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
  4. XM_024452862.1XP_024308630.1  NACHT, LRR and PYD domains-containing protein 3 isoform X3

    Conserved Domains (6) summary
    cd00116
    Location:575922
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    sd00034
    Location:699719
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
  5. XM_024452874.1XP_024308642.1  NACHT, LRR and PYD domains-containing protein 3 isoform X5

    Conserved Domains (5) summary
    cd00116
    Location:575865
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    cd08320
    Location:1093
    Pyrin_NALPs; Pyrin death domain found in NALP proteins
    sd00033
    Location:743771
    LRR_RI; leucine-rich repeat [structural motif]
    pfam05729
    Location:220389
    NACHT; NACHT domain
    pfam14484
    Location:144209
    FISNA; Fish-specific NACHT associated domain
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