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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NLRP2
NLR family pyrin domain containing 2
Chromosome 19 · 19q13.42
NCBI Gene: 55655Ensembl: ENSG00000022556.16HGNC: HGNC:22948UniProt: A8K9G6
69PubMed Papers
21Diseases
0Drugs
4Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of non-canonical NF-kappaB signal transductionprotein bindingPyrin domain bindingcytosoloocyte/zygote/embryo maturation arrest 18Beckwith-Wiedemann syndrome due to imprinting defect of 11p15CINCA syndromeresponse to xenobiotic stimulus
✦AI Summary

NLRP2 (NLR family pyrin domain containing 2) is a multifunctional protein with roles in innate immunity and reproductive development. As an inflammasome component, NLRP2 associates with PYCARD to activate caspase-1 and promote IL-1β secretion, contributing to inflammatory responses 1. However, NLRP2 exhibits dual regulatory capacity, capable of both promoting and suppressing inflammatory signaling through NF-κB pathways 2. Beyond immunity, NLRP2 functions as a critical maternal-effect gene encoding a non-core component of the subcortical maternal complex (SCMC), essential for oocyte maturation and early embryonic development 3. Loss of NLRP2 in mice causes transcriptome dysregulation in oocytes, including altered expression of histone demethylase KDM1B and disrupted DNA methylation at imprinted loci 4. Functionally, maternal NLRP2 loss impairs placental architecture and embryonic development, resulting in neural tube defects, craniofacial abnormalities, and congenital heart defects 5. Pathologically, biallelic NLRP2 variants cause female infertility with embryonic development arrest 63, while NLRP2 gene body hypomethylation associates with hepatocellular carcinoma progression 7. These findings establish NLRP2 as a bridge protein linking innate immunity with reproductive function.

Sources cited
1
NLRP2 forms inflammasomes that regulate innate immunity and can become dysregulated in autoimmune and neurodegenerative diseases
PMID: 38644450
2
NLRP2 has dual roles in promoting inflammation through inflammasome activation and downregulating inflammatory signals; functions in reproductive system remain unclear
PMID: 37735978
3
NLRP2 is a non-core component of the subcortical maternal complex; pathogenic variants cause embryonic development arrest and female infertility
PMID: 39178021
4
NLRP2 mutations are identified genetic causes of oocyte maturation arrest and embryonic arrest in human reproduction
PMID: 33895934
5
Maternal Nlrp2 loss alters oocyte transcriptome, increases expression of histone demethylase KDM1B, and disrupts DNA methylation patterns
PMID: 36976514
6
Maternal NLRP2 loss causes abnormal yolk sac vasculature, neural tube defects, craniofacial abnormalities, cardiac defects, and placental dysfunction; human biallelic NLRP2 variants cause pregnancy loss and congenital anomalies
PMID: 41454780
7
NLRP2 gene body hypomethylation is associated with hepatocellular carcinoma development and serves as a biomarker for early HCC detection
PMID: 37273114
8
NLRP2 inflammasome role in the nervous system is understudied compared to NLRP1 and NLRP3, with potential therapeutic implications in neuropathologies
PMID: 38722788
Disease Associationsⓘ21
oocyte/zygote/embryo maturation arrest 18Open Targets
0.48Moderate
Beckwith-Wiedemann syndrome due to imprinting defect of 11p15Open Targets
0.42Moderate
CINCA syndromeOpen Targets
0.18Weak
response to xenobiotic stimulusOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
ovarian cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
gliomaOpen Targets
0.07Suggestive
bladder transitional cell carcinomaOpen Targets
0.06Suggestive
strictureOpen Targets
0.06Suggestive
venous thromboembolismOpen Targets
0.06Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.05Suggestive
laryngeal carcinomaOpen Targets
0.05Suggestive
primary ovarian insufficiencyOpen Targets
0.05Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
posterior cortical atrophyOpen Targets
0.05Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.05Suggestive
Testicular regression syndromeOpen Targets
0.04Suggestive
Oocyte/zygote/embryo maturation arrest 18UniProt
Pathogenic Variants4
NM_017852.5(NLRP2):c.2537+1G>CLikely pathogenic
Oocyte/zygote/embryo maturation arrest 18
★☆☆☆2025
NM_017852.5(NLRP2):c.1961C>A (p.Ser654Ter)Pathogenic
Oocyte/zygote/embryo maturation arrest 18
☆☆☆☆2023→ Residue 654
NM_017852.5(NLRP2):c.773T>C (p.Phe258Ser)Pathogenic
Oocyte/zygote/embryo maturation arrest 18
☆☆☆☆2023→ Residue 258
NM_017852.5(NLRP2):c.2254C>T (p.Arg752Ter)Pathogenic
Oocyte/zygote/embryo maturation arrest 18
☆☆☆☆2023→ Residue 752
View on ClinVar ↗
Related Genes
NLRC4Protein interaction100%NLRP3Protein interaction100%NLRP6Protein interaction98%IL1BProtein interaction94%IL18Protein interaction93%CASP1Protein interaction93%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
40%
Lung
23%
Liver
5%
Heart
2%
Ovary
2%
Gene Interaction Network
Click a node to explore
NLRP2NLRC4NLRP3NLRP6IL1BIL18CASP1
PROTEIN STRUCTURE
Preparing viewer…
PDB9C6V · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.23LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.04 [0.89–1.23]
RankingsWhere NLRP2 stands among ~20K protein-coding genes
  • #6,825of 20,598
    Most Researched69
  • #3,777of 5,498
    Most Pathogenic Variants4
  • #12,969of 17,882
    Most Constrained (LOEUF)1.23
Genes detectedNLRP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NLRP inflammasomes in health and disease.
PMID: 38644450
Mol Biomed · 2024
1.00
2
Genetic factors as potential molecular markers of human oocyte and embryo quality.
PMID: 33895934
J Assist Reprod Genet · 2021
0.90
3
NLRP2 in health and disease.
PMID: 37735978
Immunology · 2024
0.80
4
Variants in NLRP2 and ZFP36L2, non-core components of the human subcortical maternal complex, cause female infertility with embryonic development arrest.
PMID: 39178021
Mol Hum Reprod · 2024
0.70
5
The Neglected Sibling: NLRP2 Inflammasome in the Nervous System.
PMID: 38722788
Aging Dis · 2024
0.60