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4 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NLRP8
NLR family pyrin domain containing 8
Chromosome 19 · 19q13.43
NCBI Gene: 126205Ensembl: ENSG00000179709.9HGNC: HGNC:22940UniProt: Q86W28
12PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of inflammatory responsecytoplasmanorectal malformationulcerative colitisinfectionalcohol drinking
✦AI Summary

NLRP8 is a nucleotide-binding oligomerization domain (NOD)-like receptor family member involved in inflammasome regulation and innate immune responses. As a pyrin domain-containing protein, NLRP8 functions as an inflammasome sensor that responds to pathogenic stimuli 1. Upon activation, NLRP8 assembles into multiprotein inflammasome complexes that mediate caspase-1-dependent processing of pro-IL-1β, a critical pro-inflammatory cytokine 1. NLRP8 expression is upregulated during microbial infections; specifically, Toxoplasma gondii infection significantly increases NLRP8 mRNA levels in macrophages in a time-dependent manner, facilitating innate immune responses 1. Structurally distinct from NLRP3 and other family members, NLRP8 does not interact with the hematopoietic cell kinase binding partner that engages NLRP12 2. In disease contexts, NLRP8 genetic variants associate with complex inflammatory disorders; NLRP8 polymorphisms influence chr19 obstructive pulmonary disease (COPD) severity, with specific minor alleles enriched in GOLD group A patients 3. Additionally, rare NLRP8 coding variants were investigated as potential contributors to pediatric-onset multiple sclerosis susceptibility, though statistical significance was not achieved after correction for multiple comparisons 4. These findings establish NLRP8 as a key regulator of IL-1β-mediated inflammation relevant to autoimmune and chr19 respiratory diseases.

Sources cited
1
NLRP8 is an inflammasome sensor upregulated during T. gondii infection and mediates inflammasome-regulated IL-1β secretion
PMID: 28095655
2
NLRP8 has a distinct protein structure (PYD + NBD domains) that does not bind to HCK, differentiating it from NLRP12
PMID: 32226298
3
NLRP8 rs306481 polymorphisms associate with COPD severity and IL-1β-mediated inflammation
PMID: 31601004
4
NLRP8 was investigated as a rare coding variant contributor to pediatric-onset multiple sclerosis susceptibility
PMID: 36755464
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
anorectal malformationOpen Targets
0.34Weak
ulcerative colitisOpen Targets
0.26Weak
infectionOpen Targets
0.02Suggestive
alcohol drinkingOpen Targets
0.02Suggestive
lung cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
toxoplasmosisOpen Targets
0.01Suggestive
myeloid sarcomaOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
Cowden syndrome 1Open Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
bacterial diseaseOpen Targets
0.00Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.00Suggestive
insomniaOpen Targets
0.00Suggestive
Peri-ImplantitisOpen Targets
0.00Suggestive
periodontitisOpen Targets
0.00Suggestive
cervical cancerOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
Uterine CarcinosarcomaOpen Targets
0.00Suggestive
uterine corpus endometrial carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NLRP13Shared pathway100%NLRP11Shared pathway100%ARMH4Shared pathway100%MEFVProtein interaction82%NLRP4Shared pathway50%AKNAShared pathway50%
Tissue Expression6 tissues
Brain
100%
Lung
40%
Ovary
40%
Heart
0%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
NLRP8NLRP13NLRP11ARMH4MEFVNLRP4AKNA
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q86W28
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.92 [0.77–1.10]
RankingsWhere NLRP8 stands among ~20K protein-coding genes
  • #16,512of 20,598
    Most Researched12
  • #11,251of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedNLRP8
Sources retrieved4 papers
Response time—
📄 Sources
4
1
Rare and low-frequency coding genetic variants contribute to pediatric-onset multiple sclerosis.
PMID: 36755464
Mult Scler · 2023
1.00
2
Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in
PMID: 28095655
Korean J Parasitol · 2016
0.75
3
Nucleotide binding domain and leucine-rich repeat pyrin domain-containing protein 12: characterization of its binding to hematopoietic cell kinase.
PMID: 32226298
Int J Biol Sci · 2020
0.50
4
Association of
PMID: 31601004
Genes (Basel) · 2019
0.25