The protein encoded by this gene binds arginine-vasopressin and may be involved in the arginine-vasopressin-mediated regulation of renal salt-water balance. The encoded protein also mediates inflammatory responses in the colon to allow recovery from intestinal epithelial damage and protects against tumorigenesis and the development of colitis. Finally, this protein can increase... See more...

Aliases for NLRP6 Gene

Aliases for NLRP6 Gene

  • NLR Family Pyrin Domain Containing 6 2 3 5
  • Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And Pyrin Domain Containing 6 2 3
  • NACHT, LRR And PYD Domains-Containing Protein 6 3 4
  • NACHT, Leucine Rich Repeat And PYD Containing 6 2 3
  • PYRIN-Containing APAF1-Like Protein 5 3 4
  • Angiotensin II/Vasopressin Receptor 3 4
  • PYPAF5 3 4
  • NALP6 3 4
  • NAVR/AVR 3
  • CLR11.4 3
  • NAVR 3
  • PAN3 3
  • AVR 3

External Ids for NLRP6 Gene

Previous HGNC Symbols for NLRP6 Gene

  • NALP6

Previous GeneCards Identifiers for NLRP6 Gene

  • GC11P000098

Summaries for NLRP6 Gene

Entrez Gene Summary for NLRP6 Gene

  • The protein encoded by this gene binds arginine-vasopressin and may be involved in the arginine-vasopressin-mediated regulation of renal salt-water balance. The encoded protein also mediates inflammatory responses in the colon to allow recovery from intestinal epithelial damage and protects against tumorigenesis and the development of colitis. Finally, this protein can increase activation of NF-kappa-B, activation of CASP1 through interaction with ASC, and cAMP accumulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

GeneCards Summary for NLRP6 Gene

NLRP6 (NLR Family Pyrin Domain Containing 6) is a Protein Coding gene. Diseases associated with NLRP6 include Chemical Colitis and Familial Cold Autoinflammatory Syndrome. Among its related pathways are NOD-like receptor signaling pathway. Gene Ontology (GO) annotations related to this gene include vasopressin receptor activity. An important paralog of this gene is NLRP1.

UniProtKB/Swiss-Prot Summary for NLRP6 Gene

  • As the sensor component of the NLRP6 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 NLRP6, 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. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).

Gene Wiki entry for NLRP6 Gene

Additional gene information for NLRP6 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NLRP6 Gene

Genomics for NLRP6 Gene

GeneHancer (GH) Regulatory Elements for NLRP6 Gene

Promoters and enhancers for NLRP6 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NLRP6 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NLRP6

Top Transcription factor binding sites by QIAGEN in the NLRP6 gene promoter:
  • AP-1
  • AREB6
  • ATF-2
  • CRE-BP1
  • HNF-4alpha1
  • LCR-F1
  • NF-kappaB
  • NF-kappaB1
  • NF-kappaB2
  • STAT5A

Genomic Locations for NLRP6 Gene

Genomic Locations for NLRP6 Gene
chr11:278,365-285,388
(GRCh38/hg38)
Size:
7,024 bases
Orientation:
Plus strand
chr11:278,365-285,359
(GRCh37/hg19)
Size:
6,995 bases
Orientation:
Plus strand

Genomic View for NLRP6 Gene

Genes around NLRP6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NLRP6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NLRP6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NLRP6 Gene

Proteins for NLRP6 Gene

  • Protein details for NLRP6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P59044-NLRP6_HUMAN
    Recommended name:
    NACHT, LRR and PYD domains-containing protein 6
    Protein Accession:
    P59044
    Secondary Accessions:
    • A8K9F3
    • E9PJZ8

    Protein attributes for NLRP6 Gene

    Size:
    892 amino acids
    Molecular mass:
    98768 Da
    Quaternary structure:
    • Sensor component of NLRP6 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 NLRP6 inflammasomes consists of a signal sensor component (NLRP6), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1 and, possibly, CASP4 and CASP5). Within the complex, NLRP6 and PYCARD interact via their respective 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. NLRP6 localizes at the end of each PYCARD filament. Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization. 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. 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.

    Three dimensional structures from OCA and Proteopedia for NLRP6 Gene

    Alternative splice isoforms for NLRP6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NLRP6 Gene

Post-translational modifications for NLRP6 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NLRP6 Gene

No data available for DME Specific Peptides for NLRP6 Gene

Domains & Families for NLRP6 Gene

Gene Families for NLRP6 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for NLRP6 Gene

Blocks:
  • Pyrin domain
  • Disease resistance protein signature
  • Leucine-rich repeat, ribonuclease inhibitor subtype
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NLRP6 Gene

GenScript: Design optimal peptide antigens:
  • PYRIN-containing APAF1-like protein 5 (NALP6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P59044

UniProtKB/Swiss-Prot:

NLRP6_HUMAN :
  • Belongs to the NLRP family.
Family:
  • Belongs to the NLRP family.
genes like me logo Genes that share domains with NLRP6: view

Function for NLRP6 Gene

Molecular function for NLRP6 Gene

UniProtKB/Swiss-Prot Function:
As the sensor component of the NLRP6 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 NLRP6, 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. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).
UniProtKB/Swiss-Prot Induction:
Up-regulated by rosiglitazone, a PPARG agonist, in Caco2 and HCT116 colorectal carcinoma cells (PubMed:21088234, PubMed:23470617). Down-regulated by CRH (at protein level) (PubMed:23470617).

Phenotypes From GWAS Catalog for NLRP6 Gene

Gene Ontology (GO) - Molecular Function for NLRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005000 vasopressin receptor activity ISS --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with NLRP6: view
genes like me logo Genes that share phenotypes with NLRP6: view

Animal Models for NLRP6 Gene

MGI Knock Outs for NLRP6:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NLRP6 Gene

Localization for NLRP6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NLRP6 Gene

Cytoplasm. Inflammasome. Cell membrane. Nucleus membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NLRP6 gene
Compartment Confidence
plasma membrane 4
nucleus 4
cytosol 4
extracellular 3
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for NLRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0031965 nuclear membrane IEA --
genes like me logo Genes that share ontologies with NLRP6: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NLRP6 Gene

Pathways & Interactions for NLRP6 Gene

PathCards logo

SuperPathways for NLRP6 Gene

genes like me logo Genes that share pathways with NLRP6: view

Pathways by source for NLRP6 Gene

1 KEGG pathway for NLRP6 Gene

Interacting Proteins for NLRP6 Gene

;

Gene Ontology (GO) - Biological Process for NLRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0002862 negative regulation of inflammatory response to antigenic stimulus IEA --
GO:0006954 inflammatory response IEA --
GO:0007186 G protein-coupled receptor signaling pathway IEA --
GO:0009617 response to bacterium IEA,IBA 21873635
genes like me logo Genes that share ontologies with NLRP6: view

No data available for SIGNOR curated interactions for NLRP6 Gene

Drugs & Compounds for NLRP6 Gene

No Compound Related Data Available

Transcripts for NLRP6 Gene

mRNA/cDNA for NLRP6 Gene

2 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NLRP6 Gene

No ASD Table

Relevant External Links for NLRP6 Gene

GeneLoc Exon Structure for
NLRP6

Expression for NLRP6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NLRP6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NLRP6 Gene

This gene is overexpressed in Whole Blood (x25.3) and Small Intestine - Terminal Ileum (x18.3).

Protein differential expression in normal tissues from HIPED for NLRP6 Gene

This gene is overexpressed in Gallbladder (42.6) and Heart (25.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NLRP6 Gene



Protein tissue co-expression partners for NLRP6 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NLRP6

SOURCE GeneReport for Unigene cluster for NLRP6 Gene:

Hs.352611

mRNA Expression by UniProt/SwissProt for NLRP6 Gene:

P59044-NLRP6_HUMAN
Tissue specificity: Expressed in peripheral blood leukocytes, predominantly in granulocytes and, at lower levels, in CD4(+) and CD8(+) T-cells. Expressed in colonic myofibroblasts (at protein level) (PubMed:21593405).

Evidence on tissue expression from TISSUES for NLRP6 Gene

  • Heart(2.5)
  • Intestine(2.3)
genes like me logo Genes that share expression patterns with NLRP6: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NLRP6 Gene

Orthologs for NLRP6 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NLRP6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NLRP6 31 30
  • 97.36 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NLRP6 31 30
  • 82.24 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NLRP6 31 30
  • 80.89 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nlrp6 30
  • 76.13 (n)
mouse
(Mus musculus)
Mammalia Nlrp6 17 31 30
  • 74.99 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 36 (a)
ManyToMany
-- 31
  • 33 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 29 (a)
ManyToMany
zebrafish
(Danio rerio)
Actinopterygii si:ch211-66k16.2 31
  • 26 (a)
ManyToMany
CU693495.1 31
  • 23 (a)
ManyToMany
nlrb5 31
  • 22 (a)
ManyToMany
si:ch211-66k16.28 31
  • 15 (a)
ManyToMany
Species where no ortholog for NLRP6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NLRP6 Gene

ENSEMBL:
Gene Tree for NLRP6 (if available)
TreeFam:
Gene Tree for NLRP6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NLRP6: view image

Paralogs for NLRP6 Gene

(3) SIMAP similar genes for NLRP6 Gene using alignment to 2 proteins:

  • NALP6_HUMAN
  • E9PJZ8_HUMAN
genes like me logo Genes that share paralogs with NLRP6: view

Variants for NLRP6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NLRP6 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
718504 Likely Benign: not provided 281,283(+) G/A MISSENSE_VARIANT
718545 Benign: not provided 281,692(+) G/C MISSENSE_VARIANT
720682 Likely Benign: not provided 284,256(+) C/T MISSENSE_VARIANT
770212 Benign: not provided 284,377(+) G/A SYNONYMOUS_VARIANT
785333 Benign: not provided 281,289(+) C/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NLRP6 Gene

Structural Variations from Database of Genomic Variants (DGV) for NLRP6 Gene

Variant ID Type Subtype PubMed ID
dgv1012n100 CNV gain 25217958
dgv1505n54 CNV gain 21841781
dgv186n67 CNV gain 20364138
esv32593 CNV loss 17666407
esv3891905 CNV gain 25118596
nsv1052484 CNV gain 25217958
nsv482153 CNV gain 20164927
nsv552765 CNV gain 21841781
nsv552766 CNV loss 21841781
nsv7212 OTHER inversion 18451855

Variation tolerance for NLRP6 Gene

Residual Variation Intolerance Score: 60.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.29; 76.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NLRP6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NLRP6

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NLRP6 Gene

Disorders for NLRP6 Gene

MalaCards: The human disease database

(3) MalaCards diseases for NLRP6 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search NLRP6 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NLRP6

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NLRP6: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NLRP6 Gene

Publications for NLRP6 Gene

  1. NALPs: a novel protein family involved in inflammation. (PMID: 12563287) Tschopp J … Burns K (Nature reviews. Molecular cell biology 2003) 2 3 4 54
  2. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1. (PMID: 12387869) Grenier JM … Bertin J (FEBS letters 2002) 3 4 23 54
  3. PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing. (PMID: 12019269) Wang L … Bertin J (The Journal of biological chemistry 2002) 2 3 4 54
  4. The genetics of NOD-like receptors in Crohn's disease. (PMID: 20403135) Cummings JR … Jewell DP (Tissue antigens 2010) 3 41 54
  5. Aberrant expression of NLRP3, NLRC4 and NLRP6 inflammasomes in patients with primary immune thrombocytopenia. (PMID: 30802690) Lv Y … Xie J (Thrombosis research 2019) 3 54

Products for NLRP6 Gene

Sources for NLRP6 Gene