Affinage

NLRP7

NACHT, LRR and PYD domains-containing protein 7 · UniProt Q8WX94

Length
980 aa
Mass
111.8 kDa
Annotated
2026-06-10
98 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NLRP7 is a cytoplasmic NLR protein that operates in two broad arenas: it nucleates an inflammasome in innate immune cells and it governs DNA methylation and genomic integrity in the oocyte and early embryo (PMID:22361007, PMID:41786744). Its N-terminal PYD adopts a six-helix death-fold whose electrostatic surface differs from NLRP1, providing a structural basis for signaling specificity (PMID:20547486), while its central NACHT-associated domain (NAD) mediates inter-molecular oligomerization in which the NAD and LRR of one molecule engage the NACHT of a second (PMID:25082979), and its nucleotide-binding domain binds and hydrolyzes ATP through an intact Walker A motif required for oligomerization and inflammasome activity (PMID:26143398). In macrophages NLRP7 assembles an ASC-dependent, caspase-1-activating inflammasome in response to microbial acylated lipopeptides, driving IL-1β/IL-18 maturation, pyroptosis and restriction of intracellular bacteria (PMID:22361007), a response also engaged by mycobacterial infection and by lipopeptide stimulation of amnion epithelial cells where gasdermin D is cleaved (PMID:27043315, PMID:32849565). NLRP7 protein abundance is set by constitutive ubiquitination and endolysosomal degradation that is reversed by the deubiquitinase STAMBP upon TLR ligation to potentiate inflammasome output, with USP10 performing analogous stabilizing deubiquitination at K379 in cancer cells (PMID:28492230, PMID:33838681). In reproductive contexts NLRP7 sequesters the DNMT3A inhibitor TCL1A in the cytoplasm — a complex resolved by cryo-EM — to license de novo DNA methylation, and recurrent hydatidiform mole-causing variants disrupt this interaction (PMID:41786744); it further interacts with the chromatin factors YY1 and the repressor ZBTB16 to influence DNA methylation and lineage differentiation (PMID:24105472, PMID:26121690), translocates to the nucleus during decidualization to potentiate progesterone receptor activity (PMID:28810880), and binds splicing and DNA-damage-response factors to maintain genomic integrity in early embryos (PMID:39865169). In trophoblast and choriocarcinoma cells NLRP7 acts in an inflammasome-independent mode to control proliferation, survival and immune evasion, including ELF3-driven promotion of HLA-C expression and modulation of NF-κB signaling (PMID:34203890, PMID:36980199, PMID:39052836).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2005 Medium

    Established the first functional placement of NLRP7 in innate immunity by showing it regulates IL-1β secretion, framing it as a feedback modulator rather than an inert NLR.

    Evidence Stable NLRP7 expression in THP-1 cells with LPS/IL-1β stimulation and IL-1β secretion assays

    PMID:15817483

    Open questions at the time
    • Whether NLRP7 inhibits or activates IL-1β was context-dependent and not yet reconciled
    • No complex composition or direct molecular target identified
  2. 2010 High

    Resolved the NLRP7 PYD fold at atomic resolution, providing a structural rationale for why NLRP7 signals distinctly from other PYD-containing NLRs.

    Evidence NMR 3D structure determination of the NLRP7 PYD with comparison to NLRP1 PYD

    PMID:20547486

    Open questions at the time
    • Did not define which downstream partner the PYD engages
    • No full-length protein structure
  3. 2011 Medium

    Linked NLRP7 to specific subcellular compartments and tied protein-truncating mutations to loss of its cytokine-regulatory function in patient cells.

    Evidence Immunofluorescence co-localization with Golgi/MTOC/microtubules and ELISA on patient PBMCs with truncation mutants

    PMID:22025618

    Open questions at the time
    • Functional meaning of Golgi/MTOC localization unresolved
    • Direction of cytokine regulation appeared inhibitory, conflicting with later inflammasome activation data
  4. 2012 High

    Defined NLRP7 as a bona fide inflammasome platform, showing it senses acylated lipopeptides to assemble an ASC/caspase-1 complex that matures IL-1β/IL-18, triggers pyroptosis and restricts bacteria.

    Evidence Reciprocal Co-IP of ASC/caspase-1, knockdown, multi-cytokine ELISA and bacterial replication assays in human macrophages

    PMID:22361007

    Open questions at the time
    • Direct ligand-binding event not demonstrated
    • Reconciliation with earlier inhibitory phenotypes not addressed
  5. 2014 Medium

    Identified the NAD as the engine of NLRP7 self-assembly and showed disease mutations impair oligomerization, connecting the activation mechanism to pathology.

    Evidence Yeast two-hybrid inter-domain mapping, in silico modeling and confocal microscopy of disease mutants (L398R, R693W) in HEK293T cells

    PMID:25082979

    Open questions at the time
    • No structure of the oligomer
    • Inter-domain interaction not confirmed in full-length endogenous protein
  6. 2014 Medium

    Mapped NLRP7 localization dynamics across human oogenesis and preimplantation development, indicating a polarized, stage-dependent role beyond immunity.

    Evidence High-resolution confocal and electron microscopy on human oocytes and embryos (n=164)

    PMID:25358348

    Open questions at the time
    • Molecular function at the oocyte cortex not defined
    • Mechanism of asymmetric confinement unknown
  7. 2015 High

    Demonstrated that NLRP7 is an ATP-binding ATPase whose Walker A motif is mechanistically required for oligomerization and inflammasome activation, establishing the nucleotide-dependent activation cycle.

    Evidence In vitro ATP binding/ATPase assays, Walker A mutagenesis, Co-IP and IL-1β/pyroptosis readouts in THP-1 cells

    PMID:26143398

    Open questions at the time
    • Conformational change driven by ATP hydrolysis not visualized
    • Coupling of ATPase cycle to ligand sensing unresolved
  8. 2013 Medium

    Connected NLRP7 to chromatin reprogramming by identifying YY1 as a partner and showing NLRP7 loss alters DNA methylation and trophoblast differentiation.

    Evidence Co-IP of NLRP7–YY1, knockdown in hESCs, methylation analysis and differentiation assays

    PMID:24105472

    Open questions at the time
    • Direct effect of NLRP7 on methylation machinery not defined
    • YY1-dependence of methylation changes not isolated
  9. 2015 Medium

    Showed NLRP7 physically sequesters the transcriptional repressor ZBTB16 in the cytoplasm, suggesting a mechanism by which it can regulate nuclear transcription factors from the cytoplasm.

    Evidence Yeast two-hybrid, Co-IP, native PAGE (~480 kDa complex) and confocal microscopy

    PMID:26121690

    Open questions at the time
    • Functional/transcriptional consequence of ZBTB16 sequestration not measured
    • Physiological context of the complex unclear
  10. 2016 Medium

    Extended inflammasome activation to a clinically relevant pathogen, showing virulent M. bovis engages the NLRP7 inflammasome.

    Evidence siRNA knockdown in THP-1 macrophages with M. bovis infection, caspase-1, IL-1β and pyroptosis readouts

    PMID:27043315

    Open questions at the time
    • Bacterial ligand sensed not identified
    • Single readout per assay
  11. 2017 High

    Defined a post-translational rheostat controlling NLRP7 abundance: constitutive ubiquitination/lysosomal degradation countered by STAMBP deubiquitination upon TLR ligation tunes inflammasome output.

    Evidence Ubiquitination assays, STAMBP knockdown, endolysosomal trafficking assays, BC-1471 inhibitor and IL-1β ELISA

    PMID:28492230

    Open questions at the time
    • E3 ligase responsible for constitutive ubiquitination not identified
    • Ubiquitin acceptor sites not mapped in this study
  12. 2017 Medium

    Revealed a nuclear, inflammasome-independent role in decidualization, with NLRP7 potentiating progesterone receptor activity.

    Evidence Subcellular fractionation, confocal microscopy, siRNA/lentiviral OE in T-HESCs, PR reporter and IGFBP-1/prolactin ELISA

    PMID:28810880

    Open questions at the time
    • Mechanism of nuclear translocation unknown
    • Direct interaction with PR not established
  13. 2020 Medium

    Linked NLRP7 loss-of-function to dysregulated trophoblast differentiation through BMP4 signaling, using patient-derived genetics.

    Evidence Patient iPSC trophoblast differentiation, whole transcriptome profiling and BMP pathway inhibition rescue

    PMID:32814763

    Open questions at the time
    • Molecular link between NLRP7 and BMP4 pathway not defined
    • Whether effect is cell-autonomous through methylation unresolved
  14. 2020 Medium

    Characterized NLRP7's trophoblast functions, showing it controls proliferation, syncytial and invasive differentiation and has an anti-apoptotic role, with selective IL-1β (not IL-18) output.

    Evidence Knockdown/overexpression in primary trophoblasts and cell lines with proliferation, invasion, hCG/syncytin and cytokine readouts under hypoxia

    PMID:30617930

    Open questions at the time
    • Mechanism of differential IL-1β vs IL-18 release unknown
    • Basis of anti-apoptotic effect not defined
  15. 2020 Medium

    Showed NLRP7 assembles an inflammasome in amnion epithelial cells in response to a Mycoplasma lipopeptide, extending its sensing role to gestational tissues.

    Evidence Immunofluorescence (NLRP7/ASC co-localization), Western blot for caspase-1 and gasdermin D cleavage in primary AECs

    PMID:32849565

    Open questions at the time
    • Physiological trigger in pregnancy not established
    • Direct lipopeptide binding not shown
  16. 2020 Medium

    Resolved how domain-specific patient mutations produce distinct cellular defects, separating effects on pro-IL-1β levels from defects in IL-1β processing/trafficking.

    Evidence Patient PBMC stimulation, intracellular pro/mature IL-1β staining and reconstitution with NLRP7 variant plasmids plus ASC/caspase-1

    PMID:32484253

    Open questions at the time
    • Genotype-phenotype mapping incomplete
    • Mechanistic basis of trafficking defects not defined
  17. 2021 Medium

    Demonstrated an inflammasome-independent pro-tumor function in choriocarcinoma, with NLRP7 supporting growth and limiting maternal immune response in vivo.

    Evidence Knockdown in CC cell lines, proliferation/3D assays and orthotopic mouse model with immune phenotyping

    PMID:34203890

    Open questions at the time
    • Molecular effectors of inflammasome-independent growth not fully defined
    • Mechanism of immune suppression unresolved
  18. 2021 Medium

    Identified USP10 as the deubiquitinase stabilizing NLRP7 in cancer cells via K379 and connected NLRP7 to NF-κB-driven CCL2 expression and M2 macrophage polarization.

    Evidence Co-IP/MS, ubiquitination/deubiquitination assays, K379 mutagenesis, RNA-seq, NF-κB reporter, CCL2 ELISA and in vivo tumor models

    PMID:33838681

    Open questions at the time
    • Whether STAMBP and USP10 act in the same cells unresolved
    • Direct NLRP7 control of NF-κB mechanism not defined
  19. 2023 Medium

    Distinguished NLRP7's tumor-context behavior, showing it differentially regulates NF-κB and promotes survival, dedifferentiation and metastatic colonization in choriocarcinoma versus a canonical inflammasome role in non-tumor trophoblasts.

    Evidence shRNA knockdown in JEG-3, overexpression in HTR8/SVneo, NF-κB assays and in vivo metastatic mouse model

    PMID:36980199

    Open questions at the time
    • Switch between inflammasome-dependent and -independent modes not mechanistically defined
    • Direct NF-κB target not isolated
  20. 2024 Medium

    Placed NLRP7 within an ELF3-controlled transcriptional axis governing maternal immune evasion, with NLRP7 promoting HLA-C expression via IκBα modulation opposite to NLRP2.

    Evidence ELF3 knockout in JEG-3, ELF3 enhancer-binding analysis, NLRP7/NLRP2 OE/KD with HLA-C and IκBα readouts

    PMID:39052836

    Open questions at the time
    • Direct mechanism by which NLRP7 alters IκBα kinetics not established
    • Relationship to inflammasome activity unclear
  21. 2025 High

    Provided the definitive mechanism for oocyte hypomethylation in recurrent hydatidiform mole by resolving the NLRP7–TCL1A cryo-EM structure and showing NLRP7 cytoplasmically sequesters TCL1A to license DNMT3A activity, with disease variants disrupting this interaction.

    Evidence Cryo-EM of the NLRP7–TCL1A complex, Co-IP, subcellular fractionation and variant interaction analysis

    PMID:41786744

    Open questions at the time
    • In vivo demonstration in human oocytes not performed
    • How NLRP7 activation state controls TCL1A release unresolved
  22. 2025 Medium

    Connected NLRP7 to genomic integrity in early embryos, showing it binds splicing/DNA-repair factors and that its loss causes aberrant splicing of HR genes, DNA damage and apoptosis.

    Evidence NLRP7 knockout in hESCs and blastoids, Co-IP identifying DDX39B/PRPF8/THRAP3/PARP1, RNA-seq splicing analysis, γH2AX and apoptosis assays

    PMID:39865169

    Open questions at the time
    • Which interaction directly drives the splicing defect not isolated
    • Direct vs indirect role in DNA damage response unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NLRP7 switches between its cytoplasmic inflammasome-sensing role and its nuclear/chromatin and methylation-regulatory roles, and what upstream signal directs each mode, remains unresolved.
  • No unified model integrating immune and reproductive functions
  • Direct ligand for inflammasome activation undefined
  • Full-length and oligomeric structures not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0140313 molecular sequestering activity 2 GO:0016787 hydrolase activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005794 Golgi apparatus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1
Pathway
R-HSA-1474165 Reproduction 2 R-HSA-168256 Immune System 2 R-HSA-4839726 Chromatin organization 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ASCCASP1KHDC3LSTAMBPTCL1AUSP10YY1ZBTB16
Complex memberships
NLRP7 inflammasome (NLRP7–ASC–caspase-1)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 NLRP7 (PYPAF3) inhibits caspase-1-dependent IL-1β secretion; stable expression of NLRP7 in THP-1 cells abrogated LPS-induced IL-1β production, and NLRP7 mRNA expression was induced by LPS or IL-1β stimulation, placing it as a feedback regulator of IL-1β secretion. Stable transfection in THP-1 monocytic cells, LPS/IL-1β stimulation, IL-1β secretion assays The Journal of biological chemistry Medium 15817483
2010 The N-terminal pyrin domain (PYD) of NLRP7 adopts a six-alpha-helix bundle death domain fold; helix α3 and loop α2-α3 are stabilized by a strong hydrophobic cluster, and the electrostatic surface differs from NLRP1 PYD, providing a structural basis for differential inflammasome signaling specificity. NMR spectroscopy (3D structure determination of NLRP7 PYD) The Journal of biological chemistry High 20547486
2011 NLRP7 co-localizes with the Golgi apparatus and the microtubule-organizing center (MTOC) and is associated with microtubules in peripheral blood mononuclear cells; cells from patients with NLRP7 mutations secrete low levels of IL-1β and TNF in response to LPS, and NLRP7 down-regulates pro-IL-1β synthesis; this inhibitory function is abolished by protein-truncating mutations after the Pyrin domain. Immunofluorescence co-localization, transient transfection with truncation mutants, ELISA for IL-1β/TNF from patient PBMCs The Journal of biological chemistry Medium 22025618
2012 NLRP7 assembles an inflammasome complex in human macrophages in response to microbial acylated lipopeptides; this complex is ASC-dependent, activates caspase-1, drives maturation and release of IL-1β and IL-18, induces pyroptosis, and restricts intracellular bacterial replication; it does not affect caspase-1-independent secretion of IL-6 or TNF-α. Co-immunoprecipitation (ASC/caspase-1 complex), NLRP7 knockdown, IL-1β/IL-18/IL-6/TNF-α ELISA, bacterial replication assays in human macrophages Immunity High 22361007
2012 NLRP7 and KHDC3L co-localize to a juxta-perinuclear signal consistent with the MTOC/Golgi in lymphoblastoid cell lines from normal subjects; KHDC3L mutations do not change the subcellular localization of KHDC3L but NLRP7 and KHDC3L proteins co-localize in this compartment. Immunofluorescence in lymphoblastoid cell lines European journal of human genetics : EJHG Low 23232697
2013 NLRP7 interacts with YY1 (a chromatin-binding transcription factor) in human embryonic stem cells; reduced NLRP7 levels alter DNA methylation and accelerate trophoblast lineage differentiation, demonstrating a role in chromatin reprogramming and DNA methylation. Co-immunoprecipitation (NLRP7–YY1 interaction), NLRP7 knockdown in hESCs, DNA methylation analysis, trophoblast differentiation assays Human molecular genetics Medium 24105472
2014 The NACHT-associated domain (NAD) of NLRP7 is central to its oligomeric assembly; upon activation, the NAD and part of the LRR of one NLRP7 molecule interact with the NACHT domain of a second molecule to form an oligomer. Disease-causing missense mutations L398R and R693W decrease oligomerization potential and increase aggresome formation. Yeast two-hybrid inter-domain interaction screen, in silico structural modeling, confocal microscopy of transiently transfected NLRP7 mutants in HEK293T cells Molecular human reproduction Medium 25082979
2015 The NBD of NLRP7 is an ATP-binding domain with ATPase activity; an intact Walker A motif is required for nucleotide binding, hydrolysis, NLRP7 oligomerization, inflammasome formation, and activity. THP-1 cells expressing a Walker A mutant display defective NLRP7 inflammasome activation, IL-1β release, and pyroptosis in response to acylated lipopeptides and S. aureus infection. In vitro ATP binding and ATPase assays, Walker A motif mutagenesis, co-immunoprecipitation (oligomerization), IL-1β ELISA, pyroptosis assay in THP-1 cells Molecular immunology High 26143398
2015 NLRP7 interacts with the transcriptional repressor ZBTB16; this interaction was verified by yeast two-hybrid, co-immunoprecipitation, and confocal microscopy in mammalian cells; both proteins are found in a ~480 kDa complex and co-localize in cytoplasmic juxtanuclear aggregates; overexpressed NLRP7 sequesters ZBTB16 in the cytoplasm away from the nucleus. Yeast two-hybrid (ovarian library screen), co-immunoprecipitation, native PAGE (480 kDa complex), confocal microscopy PloS one Medium 26121690
2014 NLRP7 and KHDC3L localize to the oocyte cytoskeleton and are predominant at the cortical region in growing oocytes; after first cell division they become asymmetrically confined to the outer cortical region and excluded from the cell-to-cell contact region until the blastocyst stage where they redistribute to the cytoplasm and nucleus respectively. High-resolution confocal immunofluorescence and electron microscopy on human oocytes and preimplantation embryos (n=164) Human reproduction (Oxford, England) Medium 25358348
2017 NLRP7 protein is constitutively ubiquitinated and targeted to the endolysosome for degradation; upon TLR ligation (LPS or Pam3CSK4), the deubiquitinase STAMBP deubiquitinates NLRP7, prevents its lysosomal trafficking, and increases NLRP7 protein abundance, thereby potentiating inflammasome activation and IL-1β release. A small-molecule STAMBP inhibitor (BC-1471) reduces NLRP7 levels and suppresses IL-1β release. Ubiquitination assays, STAMBP knockdown, endolysosomal trafficking assays, small-molecule inhibitor (BC-1471), IL-1β ELISA Nature communications High 28492230
2017 NLRP7 translocates to the nucleus of decidualized endometrial stromal cells and promotes progesterone receptor (PR) transcriptional activity and IGFBP-1 expression; knockdown of NLRP7 reduces decidualization markers while overexpression enhances them. Subcellular fractionation, confocal microscopy, siRNA knockdown and lentiviral overexpression in T-HESCs, PR reporter assay, ELISA for IGFBP-1 and prolactin Reproductive biology and endocrinology : RB&E Medium 28810880
2016 The NLRP7 inflammasome is activated by virulent Mycobacterium bovis Beijing strain in THP-1 macrophages, promoting IL-1β secretion, caspase-1 activation, pyroptosis induction, and upregulation of TNF-α, CCL3, and IL-1β mRNAs. NLRP7 knockdown (siRNA) in THP-1 macrophages, M. bovis infection, caspase-1 activity assay, IL-1β ELISA, pyroptosis assay PloS one Medium 27043315
2021 NLRP7 is deubiquitinated by USP10 in colorectal cancer cells; this stabilizes NLRP7 protein (K379 is an important lysine acceptor site for ubiquitination); NLRP7 promotes NF-κB nuclear translocation and CCL2 transcription, which induces polarization of pro-tumor M2-like macrophages. Co-immunoprecipitation/mass spectrometry, ubiquitination/deubiquitination assays, K379 mutagenesis, RNA sequencing, NF-κB reporter, ELISA for CCL2, flow cytometry for macrophage phenotype, in vivo tumor models Journal of experimental & clinical cancer research : CR Medium 33838681
2020 NLRP7 deficiency in patient-derived trophoblasts (iPSC model) causes precocious downregulation of pluripotency factors and excessive trophoblast differentiation; these phenotypes are dependent on BMP4 signaling, as BMP pathway inhibition corrects the excessive differentiation. Patient-derived iPSC trophoblast differentiation model, whole transcriptome profiling, BMP pathway inhibition rescue experiment Cell death & disease Medium 32814763
2020 NLRP7 inflammasome activation in trophoblast cells increases IL-1β secretion but not IL-18 secretion; NLRP7 controls trophoblast proliferation, differentiation towards syncytium, and invasive extravillous trophoblast differentiation, and has an anti-apoptotic role; NLRP7 expression is upregulated by hypoxia. NLRP7 knockdown/overexpression in primary trophoblasts and trophoblast cell lines, [3H]-thymidine proliferation assay, 2D/3D invasion cultures, xCELLigence, β-hCG/syncytin ELISA, IL-1β/IL-18 ELISA, hypoxia treatment Journal of molecular medicine (Berlin, Germany) Medium 30617930
2020 NLRP7 inflammasome assembles around the nucleus in human amnion epithelial cells (AECs) upon stimulation with FSL-1 (a Mycoplasma salivarium-derived lipopeptide), leading to NLRP7–ASC co-localization, pro-caspase-1 and gasdermin D cleavage into mature forms. Immunofluorescence (NLRP7/ASC co-localization), Western blot (pro-caspase-1 and gasdermin D cleavage), RT-qPCR, FSL-1 stimulation of primary AECs Frontiers in immunology Medium 32849565
2021 NLRP7 promotes choriocarcinoma (CC) cell proliferation, 3D organization, and tumor growth in an inflammasome-independent manner; CC cells with NLRP7 invalidated generated smaller tumors with higher maternal immune response and less metastases in an orthotopic mouse model. NLRP7 knockdown in CC cell lines, in vitro proliferation/3D culture assays, orthotopic mouse CC model, immune phenotyping Cancers Medium 34203890
2023 In choriocarcinoma (JEG-3) cells, NLRP7 functions in an inflammasome-independent manner and differentially regulates NF-κB activity (compared to non-tumor HTR8/SVneo cells where it acts inflammasome-dependently); NLRP7 increases malignant cell survival, dedifferentiation, and immune camouflage, and facilitates tumor cell colonization of the lungs in a preclinical GC model. NLRP7 knockdown (shRNA) in JEG-3, NLRP7 overexpression in HTR8/SVneo, NF-κB activity assay, in vivo metastatic mouse model Cells Medium 36980199
2024 ELF3 transactivates NLRP7 while suppressing NLRP2 in extravillous trophoblast (EVT) JEG-3 cells by binding to their shared enhancer; NLRP7 and NLRP2 have opposing effects on HLA-C expression, with NLRP7 promoting HLA-C levels (likely through modulating IκBα degradation kinetics) and NLRP2 suppressing them, implicating this axis in maternal immune evasion. ELF3 knockout in JEG-3, ChIP-like analysis of ELF3 binding to NLRP2/NLRP7 enhancer, NLRP7/NLRP2 overexpression/knockdown with HLA-C expression readout, IκBα protein level measurement Proceedings of the National Academy of Sciences of the United States of America Medium 39052836
2025 NLRP7 interacts with TCL1A (a DNMT3A inhibitor) and the cryo-EM structure of the NLRP7-TCL1A complex was determined; NLRP7 sequesters TCL1A in the cytoplasm, preventing its nuclear entry and consequent suppression of DNMT3A-mediated de novo methylation; most recurrent hydatidiform mole-causing NLRP7 variants impair the NLRP7-TCL1A interaction, providing a mechanistic explanation for oocyte hypomethylation. Cryo-EM structure determination of NLRP7-TCL1A complex, co-immunoprecipitation, subcellular fractionation (TCL1A cytoplasmic retention), interaction analysis of NLRP7 pathogenic variants, in silico pathogenicity predictions Nature communications High 41786744
2025 NLRP7 knockout in human embryonic stem cells and blastoids increases DNA damage and apoptosis; mechanistically, NLRP7 interacts with alternative splicing factors and DNA damage response proteins (DDX39B, PRPF8, THRAP3, PARP1), and its loss causes abnormal alternative splicing of homologous recombination genes (BRCA1, RAD51), compromising genomic integrity during early embryogenesis. NLRP7 knockout in hESCs and blastoids, co-immunoprecipitation identifying DDX39B/PRPF8/THRAP3/PARP1 as binding partners, RNA-seq for alternative splicing analysis, DNA damage assays (γH2AX), apoptosis assay Communications biology Medium 39865169
2020 In NLRP7-mutated patient monocytes, homozygous or compound heterozygous mutations in different NLRP7 domains cause distinct defects: abnormal intracellular pro-IL-1β levels or impaired mature IL-1β processing; plasmids encoding NLRP7 non-synonymous variants affect pro-IL-1β processing and/or trafficking together with caspase-1 and ASC. Patient PBMC LPS stimulation, ELISA for secreted IL-1β, intracellular staining for pro-IL-1β and mature IL-1β, overexpression of NLRP7 variant plasmids in cell lines, ASC/caspase-1 co-expression Clinical and experimental immunology Medium 32484253

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nature genetics 370 16462743
2012 An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity 275 22361007
2005 PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion. The Journal of biological chemistry 125 15817483
2009 Identification of 13 novel NLRP7 mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region. Journal of medical genetics 109 19246479
2007 A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles. Molecular human reproduction 103 18039680
2011 Viral infection augments Nod1/2 signaling to potentiate lethality associated with secondary bacterial infections. Cell host & microbe 95 21669398
2021 NLRP7 deubiquitination by USP10 promotes tumor progression and tumor-associated macrophage polarization in colorectal cancer. Journal of experimental & clinical cancer research : CR 92 33838681
2015 Absence of Maternal Methylation in Biparental Hydatidiform Moles from Women with NLRP7 Maternal-Effect Mutations Reveals Widespread Placenta-Specific Imprinting. PLoS genetics 79 26544189
2007 Women heterozygous for NALP7/NLRP7 mutations are at risk for reproductive wastage: report of two novel mutations. Human mutation 71 17579354
2017 Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity. Nature communications 69 28492230
2011 NLRP7 in the spectrum of reproductive wastage: rare non-synonymous variants confer genetic susceptibility to recurrent reproductive wastage. Journal of medical genetics 67 21659348
2012 Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7. European journal of human genetics : EJHG 64 23232697
2008 Gingipains from Porphyromonas gingivalis synergistically induce the production of proinflammatory cytokines through protease-activated receptors with Toll-like receptor and NOD1/2 ligands in human monocytic cells. Cellular microbiology 64 18182086
2021 NLRP7: From inflammasome regulation to human disease. Immunology 62 34021586
2011 NLRP7, a nucleotide oligomerization domain-like receptor protein, is required for normal cytokine secretion and co-localizes with Golgi and the microtubule-organizing center. The Journal of biological chemistry 57 22025618
2014 NLRP7 and KHDC3L, the two maternal-effect proteins responsible for recurrent hydatidiform moles, co-localize to the oocyte cytoskeleton. Human reproduction (Oxford, England) 55 25358348
2015 ATP binding by NLRP7 is required for inflammasome activation in response to bacterial lipopeptides. Molecular immunology 52 26143398
2013 NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation. Human molecular genetics 51 24105472
2010 Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity. The Journal of biological chemistry 50 20547486
2012 Mutations in NLRP7 and KHDC3L confer a complete hydatidiform mole phenotype on digynic triploid conceptions. Human mutation 46 23125094
2017 Maternal heterozygous NLRP7 variant results in recurrent reproductive failure and imprinting disturbances in the offspring. European journal of human genetics : EJHG 40 28561018
2011 The genetics of recurrent hydatidiform moles in China: correlations between NLRP7 mutations, molar genotypes and reproductive outcomes. Molecular human reproduction 40 21507883
2008 Synergism between TLRs and NOD1/2 in oral epithelial cells. Journal of dental research 40 18573991
2019 NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation. Journal of molecular medicine (Berlin, Germany) 38 30617930
2013 NLRP7 and the Genetics of Hydatidiform Moles: Recent Advances and New Challenges. Frontiers in immunology 38 23970884
2004 Oncogenic role of NALP7 in testicular seminomas. Cancer science 37 15596043
2015 Live births in women with recurrent hydatidiform mole and two NLRP7 mutations. Reproductive biomedicine online 36 25982095
2012 Mutations in NLRP7 are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles. Journal of medical genetics 36 22315435
2013 NLRP7 and related inflammasome activating pattern recognition receptors and their function in host defense and disease. Microbes and infection 34 23618810
2016 Virulent Mycobacterium bovis Beijing Strain Activates the NLRP7 Inflammasome in THP-1 Macrophages. PloS one 32 27043315
2017 NLRP7 contributes to in vitro decidualization of endometrial stromal cells. Reproductive biology and endocrinology : RB&E 30 28810880
2020 NLRP7 plays a functional role in regulating BMP4 signaling during differentiation of patient-derived trophoblasts. Cell death & disease 26 32814763
2014 Comprehensive genotype-phenotype correlations between NLRP7 mutations and the balance between embryonic tissue differentiation and trophoblastic proliferation. Journal of medical genetics 26 25097207
2013 Novel NLRP7 mutations in familial recurrent hydatidiform mole: are NLRP7 mutations a risk for recurrent reproductive wastage? European journal of obstetrics, gynecology, and reproductive biology 26 23880596
2017 Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization. Clinical and experimental reproductive medicine 25 28428943
2013 A genetic association study of NLRP2 and NLRP7 genes in idiopathic recurrent miscarriage. Human reproduction (Oxford, England) 25 23360675
2008 Expression of NLRP7 (PYPAF3, NALP7) protein in endometrial cancer tissues. Anticancer research 24 18751440
2022 Role of NLRP7 in Normal and Malignant Trophoblast Cells. Biomedicines 22 35203462
2022 Biallelic NLRP7 variants in patients with recurrent hydatidiform mole: A review and expert consensus. Human mutation 22 35842788
2006 Familial molar tissues due to mutations in the inflammatory gene, NALP7, have normal postzygotic DNA methylation. Human genetics 22 16874523
2013 The p.L750V mutation in the NLRP7 gene is frequent in Mexican patients with recurrent molar pregnancies and is not associated with recurrent pregnancy loss. Prenatal diagnosis 21 23354651
2013 NLRP7 or KHDC3L genes and the etiology of molar pregnancies and recurrent miscarriage. Molecular human reproduction 21 23963444
2021 NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment. Cancers 20 34203890
2019 A Novel Mutation in NLRP7 Related to Recurrent Hydatidiform Mole and Reproductive Failure. International journal of fertility & sterility 19 31037924
2018 The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure. Gut 19 30279238
2016 The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions. European journal of human genetics : EJHG 19 26956250
2018 Exome Sequencing and Genotyping Identify a Rare Variant in NLRP7 Gene Associated With Ulcerative Colitis. Journal of Crohn's & colitis 18 29211899
2014 NLRP7 inter-domain interactions: the NACHT-associated domain is the physical mediator for oligomeric assembly. Molecular human reproduction 18 25082979
2019 NLRP7 Is Involved in the Differentiation of the Decidual Macrophages. International journal of molecular sciences 17 31795138
2011 The spectrum of NLRP7 mutations in French patients with recurrent hydatidiform mole. European journal of obstetrics, gynecology, and reproductive biology 17 21439709
2009 PR3-ANCA in Wegener's granulomatosis prime human mononuclear cells for enhanced activation via TLRs and NOD1/2. Diagnostic pathology 17 19594951
1997 Effect of de-phosphorylation of linearized pAN7-1 and of addition of restriction enzyme on plasmid integration in Penicillium paxilli. Current genetics 17 9294263
2015 NLRP7, Involved in Hydatidiform Molar Pregnancy (HYDM1), Interacts with the Transcriptional Repressor ZBTB16. PloS one 15 26121690
2020 Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies. Journal of assisted reproduction and genetics 14 32592075
2019 NLRP7 is expressed in the ovine ovary and associated with in vitro pre-implantation embryo development. Reproduction (Cambridge, England) 14 31505467
2013 Recurrent pregnancy loss in a woman with NLRP7 mutation: not all molar pregnancies can be easily classified as either "partial" or "complete" hydatidiform moles. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 14 23722513
2011 Screening for NLRP7 mutations in familial and sporadic recurrent hydatidiform moles: report of 2 Tunisian families. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 14 21623199
2020 A novel NLRP7 protein-truncating mutation associated with discordant and divergent p57 immunostaining in diploid biparental and triploid digynic moles. Virchows Archiv : an international journal of pathology 13 32055942
2015 Novel Nonsense Mutation in the NLRP7 Gene Associated with Recurrent Hydatidiform Mole. Gynecologic and obstetric investigation 12 26606510
2014 No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility. Human reproduction (Oxford, England) 12 25376457
2013 No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles. Prenatal diagnosis 12 24105752
2012 NLRP7 mutation analysis in sporadic hydatidiform moles in Tunisian patients: NLRP7 and sporadic mole. Archives of pathology & laboratory medicine 12 22646272
2012 Mosaic moles and non-familial biparental moles are not caused by mutations in NLRP7, NLRP2 or C6orf221. Molecular human reproduction 12 22909446
2012 Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease. Biology open 12 23259058
2011 NLRP7 and the genetics of post-molar choriocarcinomas in Senegal. Molecular human reproduction 12 21948117
2023 Pyroptosis and Inflammasome-Related Genes-NLRP3, NLRC4 and NLRP7 Polymorphisms Were Associated with Risk of Lung Cancer. Pharmacogenomics and personalized medicine 11 37650010
2023 Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma. Functional & integrative genomics 8 37273114
2021 The genetics of recurrent hydatidiform moles in Mexico: further evidence of a strong founder effect for one mutation in NLRP7 and its widespread. Journal of assisted reproduction and genetics 8 33751332
2024 HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis. Proceedings of the National Academy of Sciences of the United States of America 7 39052836
2014 Adhesion of monocytes to periodontal fibroblasts requires activation of NOD1/2- and TLR4-mediated LFA-1 and VLA-4. Archives of oral biology 7 25791323
2012 Recurrent hydatidiform mole: detection of two novel mutations in the NLRP7 gene in two Egyptian families. European journal of obstetrics, gynecology, and reproductive biology 7 22770628
2025 NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing. Communications biology 6 39865169
2023 NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway. Cells 6 36980199
2023 Synthesis and validation of click-modified NOD1/2 agonists. Innate immunity 6 37828863
2020 Abnormal processing of IL-1β in NLRP7-mutated monocytes in hydatidiform mole patients. Clinical and experimental immunology 6 32484253
2020 Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome. Frontiers in immunology 6 32849565
2019 NLRP7 and KHDC3L variants in Chinese patients with recurrent hydatidiform moles. Japanese journal of clinical oncology 6 31220306
2021 NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss. Journal of assisted reproduction and genetics 5 34554362
2020 NOD1/2 and the C-Type Lectin Receptors Dectin-1 and Mincle Synergistically Enhance Proinflammatory Reactions Both In Vitro and In Vivo. Journal of inflammation research 5 32801829
2019 Gene Variants, mRNA and NOD1/2 Protein Levels in Tunisian Childhood Asthma. Lung 5 30874883
2024 C-type lectin 4 of Toxocara canis activates NF-ĸB and MAPK pathways by modulating NOD1/2 and RIP2 in murine macrophages in vitro. Parasitology research 4 38639821
2023 High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with NLRP7 Pathogenic Variations. Balkan journal of medical genetics : BJMG 3 37265977
2021 Reprogramming of human peripheral blood mononuclear cells from a patient suffering from recurrent hydatidiform mole to an iPSC line FAHZUi001-A carrying a homozygous p.Gln421Ter mutation in NLRP7 gene. Stem cell research 3 34087990
2009 Backbone and sidechain (1)H, (15)N and (13)C assignments of the NLRP7 pyrin domain. Biomolecular NMR assignments 3 19888692
2025 Molecular Identification and Expression Analysis of NOD1/2 and TBK1 in Response to Viral or Bacterial Infection in the Spotted Knifejaw (Oplegnathus punctatus). Animals : an open access journal from MDPI 2 40218399
2021 High-Risk Gestational Trophoblastic Neoplasia from a Homozygous NLRP7 Mutation. Gynecologic oncology reports 2 34189227
2026 TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants. Nature communications 1 41786744
2025 A sensitive bioassay to measure NOD1/2 ligands in human serum reveals differential postprandial NOD2 activation. Frontiers in nutrition 1 40635891
2024 Identification, characterization and the inflammatory regulating effect of NOD1/2 in sturgeon. Fish & shellfish immunology 1 38281612
2020 Detection of Parental Contribution to Molar Genome Leads to Diagnosis of Recurrent Hydatidiform Mole in a Family with NLRP7 Variants. Fetal and pediatric pathology 1 33252287
2018 Small interfering RNA based knock down of acute heat shock and or GGA inducible bovine heat shock protein 70 may interfere invitro expression pattern of TLR2/4 and NOD1/2. Journal of thermal biology 1 30196903
2001 Transformation of Curvularia lunata IM 2901 with pAN7-1 influences selected physiological properties of the fungus. Microbios 1 11229655
2026 Generation and characterization of human iPSC lines (FAHZJUi001-A and FAHZJUi002-A) from two familial recurrent hydatidiform mole patients carrying homozygous mutation in the NLRP7 gene. Human cell 0 41535518
2026 Artificial intelligence-driven high-content imaging decodes for NLRP7-mutant recurrent hydatidiform moles. iScience 0 42006372
2025 Is gestational trophoblastic neoplasia more common among women with recurrent hydatidiform moles and biallelic NLRP7 mutations? a 17-years prospective study from India. European journal of obstetrics, gynecology, and reproductive biology 0 40319759
2025 The retrospective data analysis of NLRP7 and KHDC3L mutations in Turkish patients with recurrent hydatidiform mole. Turkish journal of obstetrics and gynecology 0 40908712
2025 Modulation of the PGRMC1/NLRP7/HLA-C axis by autophagy is linked to both spontaneous preterm birth and gestational choriocarcinoma. Proceedings of the National Academy of Sciences of the United States of America 0 41284890
2022 [Analysis of three Chinese pedigrees affected with recurrent hydatidiform mole due to variants of NLRP7 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 36184085

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