Details for: NLRP2

Gene ID: 55655

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NLRP2

Ensembl ID: ENSG00000022556

Description: NLR family pyrin domain containing 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • extravillous trophoblast CL0008036
    CSI 2.97
    rCSI 3.68%
    PRS 99.11
  • placental villous trophoblast CL2000060
    CSI 2.55
    rCSI 3.94%
    PRS 99.09
  • syncytiotrophoblast cell CL0000525
    CSI 1.94
    rCSI 5.58%
    PRS 98.38

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NLRP2](/details-gene/55655) (NLR family pyrin domain containing 2) is a protein-coding gene located on chromosome 19q13.42. As a member of the NACHT, LRR, and PYD domains-containing (NALP) protein family, it is implicated in the regulation of apoptosis and inflammation ([Link](https://doi.org/10.1038/sj.cdd.4400774), [Link](https://doi.org/10.1016/s0960-9822(01)00056-2)). Functionally, [NLRP2](/details-gene/55655) is known to participate in the [innate immune response](/details-cell/GO:0045087) and can regulate NF-kappaB and caspase-1 activation ([Link](https://doi.org/10.1074/jbc.m406741200)). Expression data reveals a highly specialized role for this gene, with its most significant expression concentrated in placental cells, including [extravillous trophoblast](/details-cell/CL0008036) and [placental villous trophoblast](/details-cell/CL2000060). This specific expression pattern, combined with clinical findings, links mutations in [NLRP2](/details-gene/55655) to female infertility and early embryonic arrest, highlighting its critical function in early human development ([Link](https://doi.org/10.1136/jmedgenet-2018-105936)). ## Cellular Roles and Expression Landscape The expression profile of [NLRP2](/details-gene/55655) indicates a highly specialized function predominantly related to the placenta. **Overall**, the gene shows its highest significance in cell types that constitute the maternal-fetal interface. * **Top Expression Contexts:** The most significant expression is observed in [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.97), [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.55), and [syncytiotrophoblast cell](/details-cell/CL0000525) (CSI: 1.94). These cells are fundamental for embryo implantation, placental development, and nutrient exchange, suggesting that [NLRP2](/details-gene/55655) plays a crucial role in establishing and maintaining a successful pregnancy. This restricted expression pattern is consistent with its established role in reproductive biology. Studies have identified mutations in [NLRP2](/details-gene/55655) as a cause of certain forms of female infertility, which are characterized by recurrent preimplantation embryonic arrest ([Link](https://doi.org/10.1136/jmedgenet-2018-105936), [Link](https://doi.org/10.1111/cge.13858)). This suggests that its function within trophoblasts is essential for the earliest stages of embryonic development. ## Pathways and Molecular Function The functions of [NLRP2](/details-gene/55655) are primarily associated with the regulation of innate immunity and inflammation, which are critical processes for managing the immune-privileged environment of the placenta. * **Biological Processes:** [NLRP2](/details-gene/55655) is involved in the [innate immune response](/details-cell/GO:0045087), the general [inflammatory response](/details-cell/GO:0006954), and the [regulation of inflammatory response](/details-cell/GO:0050727). It also contributes to the [positive regulation of interleukin-1 beta production](/details-cell/GO:0032731) and the [apoptotic process](/details-cell/GO:0006915), both of which are vital for tissue remodeling during placentation. * **Molecular Functions:** At the molecular level, its activities are characteristic of NLR proteins, including [ATP binding](/details-cell/GO:0005524) and [PYRIN domain binding](/details-cell/GO:0032090), which are essential for the assembly of inflammasome complexes and signal transduction. * **Cellular Location:** The protein is found predominantly in the [cytoplasm](/details-cell/GO:0005737) and [cytosol](/details-cell/GO:0005829), which is consistent with its role as a component of the inflammasome, a cytosolic protein complex. The involvement of [NLRP2](/details-gene/55655) in regulating inflammatory pathways within trophoblasts is likely critical for modulating the maternal immune response to the semi-allogeneic fetus, thereby preventing rejection and supporting a healthy pregnancy. ## Research Directions The highly specific expression of [NLRP2](/details-gene/55655) in trophoblasts and its link to early embryonic failure present several compelling avenues for future research. **Proposed Hypotheses:** 1. [NLRP2](/details-gene/55655) functions as a key regulator of the trophoblast inflammasome, and its dysregulation in response to maternal or fetal stress signals (e.g., infection, metabolic dysfunction) contributes to pathologies of pregnancy such as pre-eclampsia or intrauterine growth restriction. 2. Beyond its immune function, [NLRP2](/details-gene/55655) is a critical component of the maternal-effect gene products deposited in the oocyte, where it regulates zygotic genome activation and the developmental competence of the preimplantation embryo. **Experimental Approach:** To test the first hypothesis regarding its role in pregnancy pathologies, a robust experimental model could be established. One could use CRISPR-Cas9 to knock down or knock out [NLRP2](/details-gene/55655) in human trophoblast stem cells or immortalized trophoblast cell lines (e.g., HTR-8/SVneo). These genetically modified cells could then be subjected to various stressors relevant to pre-eclampsia, such as hypoxia or inflammatory cytokines (e.g., TNF-alpha). The cellular response could be measured by quantifying the secretion of IL-1 beta and other inflammatory markers via ELISA, and changes in invasive capacity could be assessed using a Matrigel invasion assay. This would directly test whether [NLRP2](/details-gene/55655) is necessary for the proper inflammatory and functional response of trophoblasts under pathological stress. **Therapeutic Potential:** Given its highly restricted expression and essential role in embryonic development, [NLRP2](/details-gene/55655) is unlikely to be a conventional therapeutic target for inhibition in adult diseases. Systemic modulation could have severe, unintended consequences on fertility. Instead, its primary clinical relevance may lie in diagnostics and reproductive medicine. Screening for mutations in [NLRP2](/details-gene/55655) could become a standard part of genetic testing for couples experiencing recurrent pregnancy loss or in-vitro fertilization failure. Furthermore, understanding the pathways it regulates could lead to novel therapeutic strategies aimed at improving placental health and function in high-risk pregnancies, potentially by targeting downstream effectors rather than [NLRP2](/details-gene/55655) itself.

Genular Protein ID: 2838233335

Symbol: NALP2_HUMAN

Name: NACHT, LRR and PYD domains-containing protein 2

UniProtKB Accession Codes:

Q9NX02 B4DZL7 I3L0G4 Q53FL5 Q59G09 Q8IXT0 Q9BVN5 Q9H6G6 Q9HAV9 Q9NWK3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CORUM 1 CTD 1 ChEBI 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 40 ExpressionAtlas 1 GO 12 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 Pumba 1 RNAct 1 RefSeq 5 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11270363

Title: The PYRIN domain: a novel motif found in apoptosis and inflammation proteins.

PubMed ID: 11270363

DOI: 10.1038/sj.cdd.4400774

PubMed ID: 11250163

Title: The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation.

PubMed ID: 11250163

DOI: 10.1016/s0960-9822(01)00056-2

PubMed ID: 12019269

Title: PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing.

PubMed ID: 12019269

DOI: 10.1074/jbc.m203915200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15030775

Title: NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.

PubMed ID: 15030775

DOI: 10.1016/s1074-7613(04)00046-9

PubMed ID: 15456791

Title: PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages.

PubMed ID: 15456791

DOI: 10.1074/jbc.m406741200

PubMed ID: 17431422

Title: The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

PubMed ID: 17431422

DOI: 10.1038/sj.cdd.4402142

PubMed ID: 17178784

Title: Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome activation.

PubMed ID: 17178784

DOI: 10.1128/iai.01315-06

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 30877238

Title: Mutations in NLRP2 and NLRP5 cause female infertility characterised by early embryonic arrest.

PubMed ID: 30877238

DOI: 10.1136/jmedgenet-2018-105936

PubMed ID: 33020905

Title: Expanding the genetic and phenotypic spectrum of the subcortical maternal complex genes in recurrent preimplantation embryonic arrest.

PubMed ID: 33020905

DOI: 10.1111/cge.13858

Sequence Information:

  • Length: 1062
  • Mass: 120515
  • Checksum: 4DBB0F6E9C2BC8A7
  • Sequence:
    • MVSSAQMGFN LQALLEQLSQ DELSKFKYLI TTFSLAHELQ KIPHKEVDKA DGKQLVEILT 
THCDSYWVEM ASLQVFEKMH RMDLSERAKD EVREAALKSF NKRKPLSLGI TRKERPPLDV 
DEMLERFKTE AQAFTETKGN VICLGKEVFK GKKPDKDNRC RYILKTKFRE MWKSWPGDSK 
EVQVMAERYK MLIPFSNPRV LPGPFSYTVV LYGPAGLGKT TLAQKLMLDW AEDNLIHKFK 
YAFYLSCREL SRLGPCSFAE LVFRDWPELQ DDIPHILAQA RKILFVIDGF DELGAAPGAL 
IEDICGDWEK KKPVPVLLGS LLNRVMLPKA ALLVTTRPRA LRDLRILAEE PIYIRVEGFL 
EEDRRAYFLR HFGDEDQAMR AFELMRSNAA LFQLGSAPAV CWIVCTTLKL QMEKGEDPVP 
TCLTRTGLFL RFLCSRFPQG AQLRGALRTL SLLAAQGLWA QTSVLHREDL ERLGVQESDL 
RLFLDGDILR QDRVSKGCYS FIHLSFQQFL TALFYTLEKE EEEDRDGHTW DIGDVQKLLS 
GVERLRNPDL IQAGYYSFGL ANEKRAKELE ATFGCRMSPD IKQELLRCDI SCKGGHSTVT 
DLQELLGCLY ESQEEELVKE VMAQFKEISL HLNAVDVVPS SFCVKHCRNL QKMSLQVIKE 
NLPENVTASE SDAEVERSQD DQHMLPFWTD LCSIFGSNKD LMGLAINDSF LSASLVRILC 
EQIASDTCHL QRVVFKNISP ADAHRNLCLA LRGHKTVTYL TLQGNDQDDM FPALCEVLRH 
PECNLRYLGL VSCSATTQQW ADLSLALEVN QSLTCVNLSD NELLDEGAKL LYTTLRHPKC 
FLQRLSLENC HLTEANCKDL AAVLVVSREL THLCLAKNPI GNTGVKFLCE GLRYPECKLQ 
TLVLWNCDIT SDGCCDLTKL LQEKSSLLCL DLGLNHIGVK GMKFLCEALR KPLCNLRCLW 
LWGCSIPPFS CEDLCSALSC NQSLVTLDLG QNPLGSSGVK MLFETLTCSS GTLRTLRLKI 
DDFNDELNKL LEEIEEKNPQ LIIDTEKHHP WAERPSSHDF MI

Genular Protein ID: 72135222

Symbol: A8K9G6_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K9G6

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 Gene3D 3 InterPro 9 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PeptideAtlas 1 Pfam 5 RefSeq 1 SMART 2 SUPFAM 3

Sequence Information:

  • Length: 1059
  • Mass: 120326
  • Checksum: D412B5FB96E9E922
  • Sequence:
    • MVSSAQMGFN LQALLEQLSQ DELSKFKYLI TTFSLAHELQ KIPHKEVDKA DGKQLVEILT 
THCDSYWVEM ASLQVFEKMH RMDLSERAKD EVREAALKSF NKRKPLSLGI TRKERPPLDV 
DEMLERFKTE AQETKGNVIC LGKEVFKGKK PDKDNRCRYI LKTKFREMWK SWPGDSKEVQ 
VMAERYKMLI PFSNPRVLPG PFSYTVVLYG PAGLGKTTLA QKLMLDWAED NLIHKFKYAF 
YLSCRELSRL GPCSFAELVF RDWPELQDDI PHILAQARKI LFVIDGFDEL GAAPVALIED 
ICGDWEKKKP VPVLLGSLLN RVMLPKAALL VTTRPRALRD LRILAEEPIY IRVEGFLEED 
RRAYFLRHFG DEDQAMRAFE LMRSNAALFQ LGSAPAVCWI VCTTLKLQME KGEDPVPTCL 
TRTGLFLRFL CSRFPQGAQL RGALRTLSLL AAQGLWAQTS VLHREDLERL GVQESDLRLF 
LDGDILRQDR VSKGCYSFIH LSFQQFLTAL FYTLEKEEEE DRDGHAWDIG DVQKLLSGVE 
RLRNPDLIQA GYYSFGLANE KRAKELEATF GCRMSPDIKQ ELLRCDISCK GGHSTVTDLQ 
ELLGCLYESQ EEELVKEVMA QFKEISLHLN AVDVVPSSFC VKHCRNLQKM SLQVIKENLP 
ENVTASESDA EVERSQDDQH MLPFWTDLCS IFGSNKDLMG LAINDSFLSA SLVRILCEQI 
ASDTCHLQRV VFKNISPADA HRNLCLALRG HKTVTYLTLQ GNDQDDMFPA LCEVLRHPEC 
NLRYLGLVSC SATTQQWADL SLALEVNQSL TCVNLSDNEL LDEGAKLLYT TLRHPKCFLQ 
RLSLENCHLT EANCKDLAAV LVVSRELTHL CLAKNPIGNT GVKFLCEGLR YPECKLQTLV 
LWNCDITSDG CCDLTKLLQE KSSLLCLDLG LNHIGVKGMK FLCEALRKPL CNLRCLWLWG 
CSIPPFSCED LCSTLSCNQS LVTLDLGQNP LGSSGVKMLF ETLTCSSGTL RTLWLKIDDF 
NDELNKLLEE IEEKNPQLII DTEKHHPWEE RPSSHDFMI

Genular Protein ID: 3282163328

Symbol: J3KN39_HUMAN

Name: N/A

UniProtKB Accession Codes:

J3KN39

Database IDs:

ARBA 2 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 3 GO 3 Gene3D 3 GeneTree 1 HGNC 1 InterPro 9 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PeptideAtlas 1 Pfam 5 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 SMART 2 SUPFAM 3 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

Sequence Information:

  • Length: 1059
  • Mass: 120196
  • Checksum: 55CAC1EF9719A3C2
  • Sequence:
    • MVSSAQMGFN LQALLEQLSQ DELSKFKYLI TTFSLAHELQ KIPHKEVDKA DGKQLVEILT 
THCDSYWVEM ASLQVFEKMH RMDLSERAKD EVREAALKSF NKRKPLSLGI TRKERPPLDV 
DEMLERFKTE AQETKGNVIC LGKEVFKGKK PDKDNRCRYI LKTKFREMWK SWPGDSKEVQ 
VMAERYKMLI PFSNPRVLPG PFSYTVVLYG PAGLGKTTLA QKLMLDWAED NLIHKFKYAF 
YLSCRELSRL GPCSFAELVF RDWPELQDDI PHILAQARKI LFVIDGFDEL GAAPGALIED 
ICGDWEKKKP VPVLLGSLLN RVMLPKAALL VTTRPRALRD LRILAEEPIY IRVEGFLEED 
RRAYFLRHFG DEDQAMRAFE LMRSNAALFQ LGSAPAVCWI VCTTLKLQME KGEDPVPTCL 
TRTGLFLRFL CSRFPQGAQL RGALRTLSLL AAQGLWAQTS VLHREDLERL GVQESDLRLF 
LDGDILRQDR VSKGCYSFIH LSFQQFLTAL FYTLEKEEEE DRDGHTWDIG DVQKLLSGVE 
RLRNPDLIQA GYYSFGLANE KRAKELEATF GCRMSPDIKQ ELLRCDISCK GGHSTVTDLQ 
ELLGCLYESQ EEELVKEVMA QFKEISLHLN AVDVVPSSFC VKHCRNLQKM SLQVIKENLP 
ENVTASESDA EVERSQDDQH MLPFWTDLCS IFGSNKDLMG LAINDSFLSA SLVRILCEQI 
ASDTCHLQRV VFKNISPADA HRNLCLALRG HKTVTYLTLQ GNDQDDMFPA LCEVLRHPEC 
NLRYLGLVSC SATTQQWADL SLALEVNQSL TCVNLSDNEL LDEGAKLLYT TLRHPKCFLQ 
RLSLENCHLT EANCKDLAAV LVVSRELTHL CLAKNPIGNT GVKFLCEGLR YPECKLQTLV 
LWNCDITSDG CCDLTKLLQE KSSLLCLDLG LNHIGVKGMK FLCEALRKPL CNLRCLWLWG 
CSIPPFSCED LCSALSCNQS LVTLDLGQNP LGSSGVKMLF ETLTCSSGTL RTLRLKIDDF 
NDELNKLLEE IEEKNPQLII DTEKHHPWAE RPSSHDFMI