The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autop... See more...

Aliases for NLRP4 Gene

Aliases for NLRP4 Gene

  • NLR Family Pyrin Domain Containing 4 2 3 5
  • Cancer/Testis Antigen 58 2 3 4
  • Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And Pyrin Domain Containing 4 2 3
  • NACHT, LRR And PYD Domains-Containing Protein 4 3 4
  • NACHT, Leucine Rich Repeat And PYD Containing 4 2 3
  • PYRIN-Containing APAF1-Like Protein 4 3 4
  • PYRIN And NACHT-Containing Protein 2 3 4
  • PAAD And NACHT-Containing Protein 2 3 4
  • Ribonuclease Inhibitor 2 3 4
  • PYPAF4 3 4
  • NALP4 3 4
  • CT58 3 4
  • PAN2 3 4
  • RNH2 3 4
  • CLR19.5 3

External Ids for NLRP4 Gene

Previous HGNC Symbols for NLRP4 Gene

  • NALP4

Previous GeneCards Identifiers for NLRP4 Gene

  • GC19P061041
  • GC19P056347
  • GC19P052660

Summaries for NLRP4 Gene

Entrez Gene Summary for NLRP4 Gene

  • The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). [provided by RefSeq, Dec 2016]

GeneCards Summary for NLRP4 Gene

NLRP4 (NLR Family Pyrin Domain Containing 4) is a Protein Coding gene. Among its related pathways are Cytosolic sensors of pathogen-associated DNA and Yersinia infection. An important paralog of this gene is NLRP14.

UniProtKB/Swiss-Prot Summary for NLRP4 Gene

  • May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways.

Gene Wiki entry for NLRP4 Gene

Additional gene information for NLRP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NLRP4 Gene

Genomics for NLRP4 Gene

GeneHancer (GH) Regulatory Elements for NLRP4 Gene

Promoters and enhancers for NLRP4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J055836 Promoter 0.7 EPDnew 500.7 +0.4 435 0.1 ZNF316 MAX NFE2 E2F6 MAFF L3MBTL2 ATF3 PKNOX1 JUND TRIP13 NLRP11 NLRP4 ZSCAN5A
GH19J055837 Promoter/Enhancer 0.7 EPDnew dbSUPER 500.7 +0.7 734 0.1 L3MBTL2 ATF3 MGA NLRP11 NLRP4 piR-43107-145
GH19J055849 Promoter 0.3 EPDnew 500.4 +13.3 13264 0.1 NLRP4 NLRP11 piR-43107-145
GH19J055833 Enhancer 0.3 dbSUPER 500.7 -1.5 -1507 1.6 IKZF1 NLRP4 NLRP11 piR-39858-326
GH19J055831 Promoter/Enhancer 0.5 EPDnew dbSUPER 0.7 -4.1 -4081 0.1 NLRP11 NLRP4 piR-39858-326
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NLRP4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NLRP4

Top Transcription factor binding sites by QIAGEN in the NLRP4 gene promoter:
  • AML1a
  • AREB6
  • CBF-A
  • CBF-B
  • CBF-C
  • CP1A
  • CP1C
  • E47
  • NF-kappaB
  • NF-kappaB1

Genomic Locations for NLRP4 Gene

Genomic Locations for NLRP4 Gene
chr19:55,836,086-55,881,855
(GRCh38/hg38)
Size:
45,770 bases
Orientation:
Plus strand
chr19:56,347,944-56,393,221
(GRCh37/hg19)
Size:
45,278 bases
Orientation:
Plus strand

Genomic View for NLRP4 Gene

Genes around NLRP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NLRP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NLRP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NLRP4 Gene

Proteins for NLRP4 Gene

  • Protein details for NLRP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96MN2-NALP4_HUMAN
    Recommended name:
    NACHT, LRR and PYD domains-containing protein 4
    Protein Accession:
    Q96MN2
    Secondary Accessions:
    • Q86W87
    • Q96AY6

    Protein attributes for NLRP4 Gene

    Size:
    994 amino acids
    Molecular mass:
    113415 Da
    Quaternary structure:
    • Interacts with CHUK/IKKA, inhibiting its kinase activity.
    Miscellaneous:
    • [Isoform 2]: Incomplete sequence.
    SequenceCaution:
    • Sequence=AAL88672.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NLRP4 Gene

    Alternative splice isoforms for NLRP4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NLRP4 Gene

Post-translational modifications for NLRP4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NLRP4 Gene

No data available for DME Specific Peptides for NLRP4 Gene

Domains & Families for NLRP4 Gene

Gene Families for NLRP4 Gene

Protein Domains for NLRP4 Gene

Suggested Antigen Peptide Sequences for NLRP4 Gene

GenScript: Design optimal peptide antigens:
  • Ribonuclease inhibitor 2 (NALP4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96MN2

UniProtKB/Swiss-Prot:

NALP4_HUMAN :
  • The pyrin domain is sufficient for suppression of NF-kappaB activity, it adopts a typical death domain fold, but in contrast to several NLRP family pyrin domains it doesn't bind homotypically to the ASC adapter, which supports the observation that NLRP4 has no effect on IL1B activation.
  • Belongs to the NLRP family.
Domain:
  • The pyrin domain is sufficient for suppression of NF-kappaB activity, it adopts a typical death domain fold, but in contrast to several NLRP family pyrin domains it doesn't bind homotypically to the ASC adapter, which supports the observation that NLRP4 has no effect on IL1B activation.
Family:
  • Belongs to the NLRP family.
genes like me logo Genes that share domains with NLRP4: view

Function for NLRP4 Gene

Molecular function for NLRP4 Gene

UniProtKB/Swiss-Prot Function:
May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways.

Phenotypes From GWAS Catalog for NLRP4 Gene

Gene Ontology (GO) - Molecular Function for NLRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with NLRP4: view
genes like me logo Genes that share phenotypes with NLRP4: view

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NLRP4 Gene

Localization for NLRP4 Gene

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 NLRP4 gene
Compartment Confidence
cytosol 5
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
lysosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NLRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with NLRP4: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for NLRP4 Gene

Pathways & Interactions for NLRP4 Gene

genes like me logo Genes that share pathways with NLRP4: view

Gene Ontology (GO) - Biological Process for NLRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006954 inflammatory response IEA --
GO:0032479 regulation of type I interferon production TAS --
genes like me logo Genes that share ontologies with NLRP4: view

No data available for SIGNOR curated interactions for NLRP4 Gene

Drugs & Compounds for NLRP4 Gene

No Compound Related Data Available

Transcripts for NLRP4 Gene

mRNA/cDNA for NLRP4 Gene

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

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NLRP4 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11a · 11b
SP1: -
SP2:
SP3: - -
SP4: -
SP5: -

Relevant External Links for NLRP4 Gene

GeneLoc Exon Structure for
NLRP4

Expression for NLRP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NLRP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NLRP4 Gene

This gene is overexpressed in Testis (x39.0).

Protein differential expression in normal tissues from HIPED for NLRP4 Gene

This gene is overexpressed in Bone marrow stromal cell (63.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NLRP4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NLRP4

SOURCE GeneReport for Unigene cluster for NLRP4 Gene:

Hs.631533
genes like me logo Genes that share expression patterns with NLRP4: view

No data available for Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for NLRP4 Gene

Orthologs for NLRP4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for NLRP4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NLRP4 31 30
  • 98.86 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nlrp4 30
  • 65.68 (n)
mouse
(Mus musculus)
Mammalia Nlrp4c 31 30
  • 64.89 (n)
OneToMany
Nlrp4e 17 31
  • 51 (a)
Nlrp4a 31
  • 50 (a)
OneToMany
Nlrp4f 31
  • 47 (a)
OneToMany
Nlrp4b 31
  • 45 (a)
OneToMany
Nlrp4g 31
  • 45 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 30 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 30 (a)
OneToMany
Species where no ortholog for NLRP4 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)
  • cow (Bos Taurus)
  • dog (Canis familiaris)
  • 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)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • 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)
  • zebrafish (Danio rerio)

Evolution for NLRP4 Gene

ENSEMBL:
Gene Tree for NLRP4 (if available)
TreeFam:
Gene Tree for NLRP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NLRP4: view image

Paralogs for NLRP4 Gene

(15) SIMAP similar genes for NLRP4 Gene using alignment to 4 proteins:

  • NALP4_HUMAN
  • J9JIE2_HUMAN
  • K7ES09_HUMAN
  • K7ESK5_HUMAN
genes like me logo Genes that share paralogs with NLRP4: view

Variants for NLRP4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NLRP4 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
716612 Benign: not provided 55,867,859(+) G/A SYNONYMOUS_VARIANT
723868 Benign: not provided 55,877,045(+) G/A MISSENSE_VARIANT
788378 Likely Benign: not provided 55,858,672(+) G/A MISSENSE_VARIANT
rs199475740 Not Provided: not provided 55,836,542(+) G/A FIVE_PRIME_UTR_VARIANT
rs199475741 Not Provided: not provided 55,836,725(+) T/G FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for NLRP4 Gene

Structural Variations from Database of Genomic Variants (DGV) for NLRP4 Gene

Variant ID Type Subtype PubMed ID
dgv3680n100 CNV gain 25217958
dgv6582n54 CNV gain 21841781
esv1278224 CNV deletion 17803354
esv22163 CNV loss 19812545
esv2674964 CNV deletion 23128226
esv2718990 CNV deletion 23290073
esv2718991 CNV deletion 23290073
esv2718992 CNV deletion 23290073
esv2718993 CNV deletion 23290073
esv2718994 CNV deletion 23290073
esv2718996 CNV deletion 23290073
esv2718997 CNV deletion 23290073
esv2718998 CNV deletion 23290073
esv2718999 CNV deletion 23290073
esv2719000 CNV deletion 23290073
esv3575075 CNV gain 25503493
esv3644849 CNV gain 21293372
esv3644850 CNV loss 21293372
esv3644851 CNV gain 21293372
esv3644852 CNV gain 21293372
esv3644853 CNV loss 21293372
esv3893253 CNV loss 25118596
nsv1057383 CNV gain 25217958
nsv1058122 CNV gain 25217958
nsv1064105 CNV gain 25217958
nsv138082 CNV deletion 16902084
nsv507901 OTHER sequence alteration 20534489
nsv510927 OTHER complex 20534489
nsv580346 CNV gain 21841781
nsv820912 CNV deletion 20802225

Variation tolerance for NLRP4 Gene

Residual Variation Intolerance Score: 68.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.78; 33.68% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NLRP4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NLRP4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NLRP4 Gene

Disorders for NLRP4 Gene

Additional Disease Information for NLRP4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for NLRP4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NLRP4 Gene

Publications for NLRP4 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. NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4. (PMID: 22388039) Cui J … Wang RF (Nature immunology 2012) 3 4 54
  4. Structural and functional analysis of the NLRP4 pyrin domain. (PMID: 22928810) Eibl C … Peti W (Biochemistry 2012) 3 4 54
  5. The genetics of NOD-like receptors in Crohn's disease. (PMID: 20403135) Cummings JR … Jewell DP (Tissue antigens 2010) 3 41 54

Products for NLRP4 Gene

Sources for NLRP4 Gene