Affinage

NPRL2

GATOR1 complex protein NPRL2 · UniProt Q8WTW4

Round 2 corrected
Length
380 aa
Mass
43.7 kDa
Annotated
2026-04-29
130 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPRL2 is a core subunit of the GATOR1 complex (with DEPDC5 and NPRL3) that functions as a GTPase-activating protein (GAP) for RagA/RagB GTPases to negatively regulate mTORC1 signaling in response to amino acid availability, thereby controlling autophagy, cell growth, and metabolic homeostasis. Cryo-EM structures show NPRL2 bridges DEPDC5 and NPRL3 within GATOR1, and Arg-78 of NPRL2 serves as the catalytic arginine finger essential for stimulating GTP hydrolysis on RagA (PMID:29590090, PMID:30651352). Loss of NPRL2 causes constitutive mTORC1 hyperactivation, leading to impaired autophagy, defective lysosomal cobalamin processing, disrupted hematopoiesis, and spontaneous seizures with excitatory/inhibitory imbalance attributable in part to mTORC1-dependent upregulation of Scn1A and glycine-NMDA receptor dysregulation (PMID:26166573, PMID:35165201, PMID:35602938). Germline NPRL2 mutations cause familial focal epilepsy with focal cortical dysplasia in humans, and somatic inactivation across multiple cancer types identifies NPRL2 as a tumor suppressor that promotes DNA damage checkpoint signaling and cisplatin sensitivity (PMID:26505888, PMID:20700484, PMID:23723238).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 Medium

    Identification of NPRL2 as a candidate tumor suppressor in a recurrently deleted 3p21.3 region established the gene's potential relevance to lung cancer biology and provided initial structural annotation including homology to yeast NPR2.

    Evidence Homozygous deletion mapping and sequence analysis in lung cancer cell lines

    PMID:11085536

    Open questions at the time
    • No functional data demonstrating tumor suppressor activity
    • Homology to yeast NPR2 not yet mechanistically exploited
  2. 2002 Medium

    Ectopic expression of NPRL2 inhibited lung cancer cell growth and suppressed xenograft tumors, providing the first functional evidence for tumor suppressor activity.

    Evidence Adenovirus-mediated gene transfer in NPRL2-deficient lung cancer cells, xenograft and metastasis models in nude mice

    PMID:11980673 PMID:15374952

    Open questions at the time
    • Mechanism of growth suppression unknown
    • No molecular target or pathway identified
  3. 2009 High

    Discovery that yeast Npr2-Npr3 form a conserved complex required for TORC1 inactivation upon amino acid starvation linked NPRL2 to the TOR signaling pathway for the first time.

    Evidence Genome-wide reverse genetic screen, co-immunoprecipitation of yeast and human NPRL2-NPRL3 heterodimer

    PMID:19521502

    Open questions at the time
    • Mechanism of TORC1 inhibition (direct vs. indirect) unknown
    • Mammalian pathway components not yet defined
  4. 2010 Medium

    NPRL2 was shown to activate the ATM-Chk1/Chk2 DNA damage checkpoint pathway and sensitize cancer cells to cisplatin, revealing a role in DNA damage signaling distinct from nutrient sensing.

    Evidence Western blotting for checkpoint kinases, kinase activity assays, cell cycle analysis, in vivo xenograft

    PMID:17018626 PMID:20700484

    Open questions at the time
    • Whether DNA damage signaling is mTORC1-dependent or independent not resolved
    • Direct molecular mechanism linking NPRL2 to ATM activation unknown
  5. 2013 High

    The landmark identification of GATOR1 (DEPDC5-NPRL2-NPRL3) as a GAP for RagA/RagB unified NPRL2's tumor suppressor and nutrient-sensing roles by placing it as a direct negative regulator of mTORC1's amino acid sensing arm.

    Evidence Affinity purification/mass spectrometry, in vitro GAP activity assay, siRNA epistasis with GATOR2, cancer mutation analysis

    PMID:23723238

    Open questions at the time
    • Catalytic mechanism and which residue provides GAP activity unknown
    • Structural basis of GATOR1-Rag interaction unresolved
  6. 2014 High

    Multiple studies established that the NPRL2-NPRL3 heterodimer acts upstream of Rag GTPases in both yeast and Drosophila to regulate autophagy and TORC1, and revealed additional roles in nitrogen metabolism and BRCA1 stability via HERC2 interaction.

    Evidence Yeast genetic epistasis with Gtr1/Gtr2, Drosophila lysosomal localization and oogenesis phenotypes, Co-IP of NPRL2-HERC2 and HR repair assays

    PMID:24786828 PMID:25046117 PMID:25480944 PMID:25515537

    Open questions at the time
    • HERC2-BRCA1 mechanism not confirmed as mTORC1-dependent or independent
    • Autophagy role in mammalian NPRL2 loss not yet characterized in vivo
  7. 2015 High

    NPRL2 knockout mice revealed essential roles in embryonic viability, fetal liver hematopoiesis, and lysosomal cobalamin processing, demonstrating that GATOR1-mTORC1 regulation has metabolic consequences beyond canonical mTOR signaling, and human genetic studies established NPRL2 mutations as a cause of familial focal epilepsy.

    Evidence Conditional KO mice with metabolomics and cyanocobalamin rescue; targeted sequencing of 404 epilepsy patients with linkage analysis

    PMID:26166573 PMID:26505888

    Open questions at the time
    • How mTORC1 hyperactivation disrupts lysosomal acidification mechanistically unclear
    • Genotype-phenotype correlations for different NPRL2 epilepsy mutations not established
  8. 2018 High

    Cryo-EM structures of GATOR1 revealed that NPRL2 serves as the architectural linker between DEPDC5 and NPRL3, and the NPRL2-NPRL3 heterodimer directly contacts RagA for GAP activity, resolving the structural basis of GATOR1 function.

    Evidence Cryo-EM at sub-4Å resolution with biochemical GAP assays

    PMID:29590090

    Open questions at the time
    • Catalytic residue not yet identified
    • Transition between inhibitory and GAP binding modes not mechanistically resolved
  9. 2019 High

    Identification of Arg-78 as the catalytic arginine finger of NPRL2 defined the atomic mechanism of GATOR1's GAP activity and explained why this residue is recurrently mutated in cancer.

    Evidence Site-directed mutagenesis of Arg-78, in vitro GTP hydrolysis assays, mTORC1 signaling readouts

    PMID:30651352

    Open questions at the time
    • Full catalytic cycle and conformational changes during GAP reaction not structurally captured
    • Cancer-associated mutations beyond Arg-78 not functionally characterized
  10. 2022 High

    Neuron-specific Nprl2 knockout mouse models revealed that mTORC1 hyperactivation causes seizures through specific downstream effectors including upregulation of the voltage-gated sodium channel Scn1A and glycine-NMDA receptor dysregulation, identifying tractable therapeutic targets.

    Evidence Conditional KO in glutamatergic neurons and dorsal telencephalon, electrophysiology, rapamycin rescue of Scn1A upregulation, metabolomics identifying glycine accumulation, NMDA receptor pharmacology

    PMID:34965576 PMID:35165201 PMID:35602938

    Open questions at the time
    • Whether Scn1A and glycine pathways are independent or converging downstream of mTORC1 is unclear
    • Cell-type-specific consequences of NPRL2 loss in inhibitory neurons not addressed
  11. 2024 Medium

    NPRL2 was linked to regulation of the tumor immune microenvironment through TRIM16-mediated Galectin-3 degradation preventing CD8+ T cell cuproptosis, and gene therapy in humanized mice showed NPRL2 restores anti-tumor immunity in KRAS/STK11-mutant NSCLC.

    Evidence Co-IP and ubiquitination assays for NPRL2-TRIM16-Gal-3 axis; humanized mouse models with immune cell depletion experiments

    PMID:39367988 PMID:39932765

    Open questions at the time
    • TRIM16-Gal-3 axis not confirmed as mTORC1-dependent
    • Whether immune-modulatory effects are separable from cell-autonomous tumor suppression not resolved
    • Single-lab findings awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the GATOR1 GAP catalytic cycle at atomic resolution, the mechanistic relationship between NPRL2's mTORC1-dependent and apparently mTORC1-independent functions (DNA damage, HERC2-BRCA1, UBE2M-neddylation), and whether therapeutic mTORC1 inhibition can substitute for NPRL2 loss across all disease contexts.
  • No full catalytic cycle structure of GATOR1 engaged with RagA-GTP
  • mTORC1-independent functions lack reconstitution with purified components
  • Genotype-phenotype relationships for clinical NPRL2 variants remain limited

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 2 GO:0005764 lysosome 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-9612973 Autophagy 4 R-HSA-5357801 Programmed Cell Death 3
Partners
DEPDC5HERC2NPRL3PDK1RPTORRRAGATRIM16UBE2M
Complex memberships
GATOR1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Yeast Npr2 and Npr3 form a heterodimer complex that is required for inactivation of TORC1 in response to amino acid starvation, but not carbon starvation or rapamycin; the human homologs NPRL2 and NPRL3 also co-immunoprecipitate, indicating the complex is evolutionarily conserved. Loss of Npr2/Npr3 prevents dephosphorylation of TORC1 effector Npr1 and fails to activate transcription factors Gln3/Gat1 upon amino acid starvation. Genome-wide reverse genetic screen (flow cytometry-based reporter), biochemical purification, co-immunoprecipitation of yeast and human homologs PLoS genetics High 19521502
2000 NPRL2/Gene21 was identified as a candidate tumor suppressor gene residing in the ~630-kb lung cancer homozygous deletion region on chromosome 3p21.3; the gene encodes a protein with sequence homology to yeast NPR2 and contains a bipartite nuclear localization signal, a protein-binding domain, and similarity to the MutS core domain. Homozygous deletion mapping, genomic sequencing, transcript mapping, sequence analysis Cancer research Medium 11085536
2002 Forced adenovirus-mediated expression of wild-type NPRL2 in 3p21.3-deficient lung cancer cells (H1299, A549) significantly inhibited tumor cell growth by inducing apoptosis and altering cell cycle processes; systemic administration also suppressed tumor xenograft growth and inhibited lung metastases in nude mice. Adenovirus-mediated gene transfer, in vitro proliferation and apoptosis assays, in vivo xenograft and metastasis models Cancer research Medium 11980673
2004 NPRL2/G21 functions as a tumor suppressor: it has inactivating mutations in renal, lung, and cervical carcinoma cell lines, tet-controlled NPRL2 transgenes suppress tumor cell growth on plastic dishes, and NPRL2 suppresses tumor formation in SCID mice. The protein contains a nuclear localization signal and a nitrogen permease regulator 2 domain. Mutation screening, tet-controlled transgene expression, growth suppression assay, SCID mouse tumor formation assay Cancer research Medium 15374952
2003 Disruption of yeast NPR2 confers resistance to cisplatin and cross-resistance to doxorubicin, without altering drug accumulation. NPR2 and SKY1 (SR-protein-specific kinase) are epistatic for cisplatin/doxorubicin sensitivity, placing NPR2 in the same pathway as SKY1 for mediating cytotoxicity of these anticancer drugs. Clonogenic survival assays, double-knockout epistasis analysis, drug accumulation measurement Molecular pharmacology Medium 12869630
2006 Restoration of NPRL2 expression in NPRL2-negative, cisplatin-resistant non-small-cell lung cancer cells resensitizes them to cisplatin, resulting in ~40% greater inhibition of viability and 2–3-fold increase in apoptosis via caspase activation. Combination treatment with NPRL2 nanoparticles and cisplatin overcame cisplatin resistance in an orthotopic mouse model. Nanoparticle-mediated gene transfer, cell viability assays, apoptosis (caspase activation) assays, orthotopic mouse model Cancer research Medium 17018626
2008 TUSC4/NPRL2 physically interacts with PDK1 via its N-terminal 133 amino acids and suppresses Src-dependent tyrosine phosphorylation and activation of PDK1 in vitro and in cells. Deletion of the N-terminal domain abolishes the inhibitory effect, demonstrating that complex formation is required for TUSC4-mediated PDK1 inactivation. TUSC4 silencing promotes cell proliferation; ectopic TUSC4 inactivates PDK1 downstream signaling including Akt and p70 S6 kinase. E. coli two-hybrid screening, co-immunoprecipitation, in vitro kinase assay, domain deletion analysis, siRNA knockdown Cancer science Medium 18616680
2010 NPRL2 sensitizes non-small-cell lung cancer cells to cisplatin by activating the DNA damage checkpoint pathway: NPRL2 promotes phosphorylation of ATM and downstream γ-H2AX formation, increases Chk1 and Chk2 kinase activity, upregulates Cdc25A and Cdc25C, and leads to G2/M cell cycle arrest. NPRL2 + cisplatin combination activates Chk2 in pleural metastases xenografts in mice. Gene transfer, Western blotting for checkpoint proteins, kinase activity assays, cell cycle analysis (flow cytometry), in vivo xenograft model PloS one Medium 20700484
2011 In yeast, Iml1p, Npr2p, and Npr3p form a complex (Iml1p-Npr2p-Npr3p) that is selectively required for non-nitrogen-starvation-induced autophagy. During this autophagy, Iml1p localizes to preautophagosomal structures (PAS) or non-PAS puncta, and loss of any complex member strongly impairs autophagosome formation. A conserved domain in Iml1p is required for both autophagy induction and complex formation. Visual screen in yeast deletion collection, ultrastructural analysis (EM), live-cell imaging of PAS localization, domain deletion analysis Molecular biology of the cell High 21900499
2013 GATOR1, composed of DEPDC5, NPRL2, and NPRL3, is a GTPase-activating protein (GAP) for RagA and RagB that negatively regulates the amino acid-sensing branch of the mTORC1 pathway. Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation; GATOR1 components are mutated in human cancer. In cancer cells with inactivating GATOR1 mutations, mTORC1 is hyperactive and insensitive to amino acid starvation. Affinity purification/mass spectrometry, GAP activity assay for RagA/B, siRNA knockdown, epistasis analysis with GATOR2, cancer mutation analysis Science High 23723238
2014 In yeast, Npr2-Npr3 function upstream of Gtr1-Gtr2 (Rag GTPase homologs) to inactivate TORC1 and induce autophagy. Npr2-Npr3 promote GDP loading of Gtr1 (RagA homolog), and Gtr2 (RagC homolog) directly binds the TORC1 subunit Kog1 (Raptor homolog). GDP-bound Gtr1 induces autophagy in a manner dependent on direct Gtr2-Kog1 binding. The mammalian homologs NPRL2 and NPRL3 were also shown to be involved in regulation of autophagy. Genetic screen, epistasis analysis with Gtr1/Gtr2 mutants, localization studies (vacuole), binding assays (Gtr2-Kog1 interaction) Autophagy High 25046117
2014 In Drosophila, Nprl2 and Nprl3 physically interact and localize to lysosomes and autolysosomes. They inhibit TORC1 signaling in the female germline in response to amino acid starvation, and this inhibition is critical for female fertility. Nprl2/3 work in concert with Tsc1/2 to fine-tune TORC1 activity, and Tsc1 is a critical downstream effector of Akt1 in the germline. Co-immunoprecipitation, immunofluorescence localization to lysosomes/autolysosomes, genetic loss-of-function, TORC1 signaling readouts in oogenesis Cell death and differentiation High 24786828
2014 Yeast Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites. Npr2-deficient yeast metabolize glutamine into nitrogenous metabolites and maintain high S-adenosyl methionine (SAM) levels instead of accumulating glutamine as wild-type cells do under nutrient-limited conditions. Methionine supplementation stimulates glutamine consumption for nitrogenous metabolite synthesis in wild-type yeast, demonstrating integration of sulfur amino acid signals with nitrogen utilization via the Npr2 complex. Metabolomics (NMR/MS), genetic analysis of Npr2-deficient yeast, nutrient supplementation experiments Science signaling Medium 25515537
2015 NPRL2 mutations cause familial focal epilepsy in humans; NPRL2 mutations make mTOR signaling resistant to amino acid deprivation, and some patients have focal epilepsy associated with brain malformations. Together with NPRL3 and DEPDC5 mutations (all GATOR1 components), GATOR1 gene mutations are the most significant cause of familial focal epilepsy identified to date. Targeted capture and next-generation sequencing of 404 epilepsy patients, exome sequencing of two families, linkage analysis Annals of neurology Medium 26505888
2015 NPRL2 is required for mouse viability and fetal liver hematopoiesis. NPRL2 KO embryos have reduced methionine levels and defective cobalamin (vitamin B12) processing: NPRL2 KO liver and MEFs show impaired lysosomal acidification, defective processing of the cobalamin-transport protein transcobalamin 2, and impaired cobalamin-dependent methionine synthesis from homocysteine. Supplementation with cyanocobalamin rescues the methionine synthesis defect. Conditional knockout mice, metabolomics (methionine levels), lysosomal acidification assays, transcobalamin 2 processing assays, cyanocobalamin rescue Cell reports High 26166573
2015 NPRL2 interacts with Raptor (mTORC1 subunit) in an amino acid-dependent manner to positively regulate mTORC1 activity. In amino acid sufficiency, NPRL2 binds Raptor to activate mTORC1; in amino acid scarcity, NPRL2 preferentially binds the dominant-negative RagA(GDP)/RagD(GTP) heterodimer to inhibit mTORC1. NPRL2 localizes predominantly to lysosomal membranes. A 'seesaw' model is proposed in which NPRL2 binding to Raptor vs. Rag GTPases determines mTORC1 activation state. Co-immunoprecipitation with Raptor and Rag GTPase mutants, lysosomal localization (immunofluorescence), Drosophila in vivo validation Cellular signalling Low 26582740
2010 Yeast Npr2 is a phosphoprotein and target of the SCF(Grr1) E3 ubiquitin ligase. Phosphorylated Npr2 accumulates in grr1Δ mutants; Npr2 is stabilized by proteasome inactivation. Phosphorylation-dependent instability depends on casein kinases Yck1 and Yck2. Npr2 is required for robust growth on ammonium or urea nitrogen sources and for efficient meiosis completion. Mass spectrometry identification, genetic analysis of grr1Δ/proteasome mutants, casein kinase deletion analysis, growth assays on defined nitrogen sources Eukaryotic cell Medium 20154027
2018 Cryo-EM structures of GATOR1 and GATOR1-Rag GTPase complexes reveal that GATOR1 adopts an extended architecture with a central cavity; NPRL2 serves as a linker between DEPDC5 and NPRL3. The NPRL2-NPRL3 heterodimer contacts RagA to execute GAP activity (GTP hydrolysis stimulation), while DEPDC5 contacts the Rag heterodimer in an inhibitory mode. At least two binding modes exist between Rag GTPases and GATOR1. Cryo-electron microscopy, biochemical GAP activity assays, co-immunoprecipitation Nature High 29590090
2019 Arg-78 of NPRL2 is the arginine finger that catalyzes GATOR1's GAP function (stimulated GTP hydrolysis by RagA). Substitution of Arg-78 renders mTORC1 signaling insensitive to amino acid starvation. This residue is frequently mutated in cancers such as glioblastoma. The GAP mode of GATOR1-Rag interaction is distinct from the inhibitory mode previously captured structurally. Site-directed mutagenesis, in vitro GTP hydrolysis assays, co-immunoprecipitation, structural analysis The Journal of biological chemistry High 30651352
2017 Overexpression of NPRL2 in cells with active p53 induces NOX2-dependent production of reactive oxygen species and DNA damage; overexpressed NPRL2 accumulates in the nucleus together with apoptosis-inducing factor (AIF). These events are accompanied by p53 phosphorylation, DNA damage response activation, and G1 arrest followed by apoptosis. In p53-negative cells, NPRL2 overexpression leads to CHK1 or CHK2 activation and G2/M arrest. These functions are distinct from NPRL2's role in mTORC1 regulation. Overexpression in multiple cell lines, ROS measurement, nuclear fractionation/localization, co-localization with AIF, flow cytometry for cell cycle, Western blotting for DNA damage markers Scientific reports Medium 29127423
2018 NPRL2 enhances autophagy in castration-resistant prostate cancer (CRPC) and promotes resistance to Everolimus (an mTOR inhibitor). NPRL2 silencing increases mTOR signaling activity, attenuates autophagy, and increases apoptosis in Everolimus-treated CRPC cells. In xenograft mouse models, NPRL2-silenced tumors show increased sensitivity to Everolimus associated with autophagy attenuation and apoptosis. siRNA knockdown, Western blotting for mTOR/autophagy markers, apoptosis assays, xenograft mouse model The Prostate Medium 30178500
2014 TUSC4/NPRL2 functions as a tumor suppressor by physically interacting with the E3 ligase HERC2, which prevents BRCA1 degradation through the ubiquitination pathway. TUSC4/NPRL2 silencing enhances BRCA1 polyubiquitination and degradation, leading to marked reduction in homologous recombination repair efficiency. TUSC4 silencing was sufficient to transform normal mammary epithelial cells and enhance sensitivity to PARP inhibitors. Global expression analysis, Co-immunoprecipitation (TUSC4-HERC2 interaction), ubiquitination assay, HR repair efficiency assay, in vitro transformation, in vivo tumorigenesis Cancer research Medium 25480944
2016 In fission yeast, Npr2-Npr3 (NPRL2-NPRL3 homologs) function together with Lam2 (LAMTOR2 homolog) as a tether for GDP-bound Gtr1 to the vacuolar membrane, thereby suppressing TORC1 activity. Loss of Lam2, Gtr1, Gtr2, Npr2, or Npr3 all disinhibit TORC1 under nitrogen depletion. Lam2 physically interacts with Npr2 and Gtr1. Genetic phenocopy analysis, TORC1 activity assay (Rps6 phosphorylation), co-immunoprecipitation (Lam2-Npr2-Gtr1), localization studies PloS one Medium 27227887
2022 Conditional deletion of Nprl2 from mouse dorsal telencephalon (Emx1-Cre) causes spontaneous seizures and dysmorphic enlarged neuronal cells with increased mTORC1 signaling, recapitulating features of human GATORopathy. Chronic rapamycin administration dramatically prolonged survival and inhibited seizures, but rapamycin benefit after withdrawal was less durable in Nprl2-cKO than Depdc5-cKO mice. Conditional knockout mice (Cre-lox), EEG seizure monitoring, histological analysis of neuronal morphology, mTORC1 signaling assays (phospho-S6), rapamycin treatment Human molecular genetics High 34965576
2022 Loss of NPRL2 expression in mouse excitatory glutamatergic neurons causes seizures and early lethality consistent with SUDEP. NPRL2 deficiency increases mTORC1-dependent signaling, alters brain amino acid homeostasis, reduces dendritic branching, and increases action potential strength. Loss of NPRL2 elevates expression of epilepsy-linked voltage-gated sodium channel Scn1A in neurons, and this upregulation is prevented by rapamycin treatment, placing Scn1A regulation downstream of NPRL2-mTORC1. Neuron-specific conditional knockout, electrophysiology (action potential recordings), sodium channel expression (Western blot/qPCR), rapamycin rescue, metabolomics (amino acid profiling) eNeuro High 35165201
2022 NPRL2 down-regulation in HCC increases Rag GTPase and mTOR activation and inhibits autophagy in vitro and in vivo. NPRL2 knockdown reduces expression of NPRL3 and DEPDC5 (the other GATOR1 subunits), suggesting NPRL2 stabilizes the complex. NPRL2-silenced cells showed enhanced proliferation, migration, and colony formation. siRNA/shRNA knockdown, subcutaneous and orthotopic xenograft mouse models, Western blotting for mTOR/Rag/autophagy markers Hepatology communications Medium 36321403
2019 Loss of Nprl2 in Drosophila decreases lifespan, causes age-related digestive dysfunction (distended crop, food accumulation, decreased crop contraction, short gut length, high intestinal stem cell proliferation), and metabolic dysfunction. All age-related phenotypes are rescued by decreasing TORC1 activity, demonstrating that Nprl2-mediated TORC1 inhibition protects against digestive tract senescence. Nprl2 loss-of-function mutation in Drosophila, lifespan assays, intestinal morphology and function assays, TORC1 inhibition rescue (rapamycin/genetic) Aging Medium 31712450
2021 In a mouse model with neocortical loss of Nprl2, increased mTORC1 signaling produces spontaneous seizures with excitatory/inhibitory imbalance (increased EPSC, decreased IPSC frequencies). Proteomic and metabolomic analyses reveal increases in glycine levels, and glycine actions on NMDA receptors contribute to both electrophysiological and survival phenotypes. This identifies glycine-NMDA receptor signaling as a downstream consequence of NPRL2 loss and mTORC1 hyperactivation. Conditional Nprl2 KO mouse, electrophysiology (patch clamp), proteomics, metabolomics (glycine measurement), pharmacological manipulation of NMDA receptors iScience High 35602938
2021 E2F1 binds to the NPRL2 promoter and activates its transcription in prostate cancer cells. FOXO1 interacts with E2F1 and weakens E2F1 binding to the NPRL2 promoter, thereby suppressing NPRL2 transcription and inhibiting prostate cancer cell proliferation. NPRL2 inhibition significantly reduces E2F1-enhanced cell proliferation. ChIP-seq data analysis (Cistrome), dual-luciferase assay, ChIP-qPCR, co-immunoprecipitation (FOXO1-E2F1), cell proliferation/colony formation assays Cell biology international Medium 34459063
2021 NPRL2 interacts with UBE2M (a neddylation E2 enzyme), and this interaction increases NPRL2 protein stability by reducing its polyubiquitination and proteasomal degradation. NPRL2 cooperatively enhances UBE2M-mediated neddylation, facilitating degradation of substrates of Cullin-RING E3 ubiquitin ligases (CRLs). Depletion of NPRL2 or UBE2M significantly increases sensitivity of CRPC cells to the PARP inhibitor niraparib. Co-immunoprecipitation (NPRL2-UBE2M), immunofluorescence, ubiquitination assay, neddylation assay, in vitro and in vivo drug sensitivity assays Experimental cell research Medium 33905671
2025 NPRL2 gene therapy in humanized mice bearing KRAS/STK11/anti-PD1-resistant NSCLC tumors reduces lung metastases significantly, correlating with increased infiltration of cytotoxic T cells and HLA-DR+ DCs, and decreased regulatory T cells and MDSCs. Stable NPRL2 expression downregulates MAPK and AKT-mTOR signaling and increases colony-formation inhibition and carboplatin sensitivity. CD8-T cell, macrophage, and CD4-T cell depletion abolishes the antitumor effect. IFNγ, CD8b, TBX21 are increased; FOXP3, TGFB1/B2, IL-10RA, and T-cell co-inhibitory molecules are downregulated. Humanized mouse model (CD34+ stem cell transplant), in vivo tumor growth assays, immune cell depletion experiments, flow cytometry of TME immune populations, protein expression profiling eLife Medium 39932765
2024 NPRL2 promotes TRIM16 expression (via inactivation of ERK1/2), and TRIM16 mediates ubiquitination-dependent degradation of Galectin-3 (Gal-3), reducing Gal-3 secretion from glioma cells. Secreted Gal-3 triggers copper uptake and cuproptosis in CD8+ T cells; NPRL2 expression thus protects CD8+ T cells from Gal-3-mediated cuproptosis and increases their recruitment. Clinical samples show NPRL2 positively correlates with TRIM16 and negatively correlates with Gal-3 and CD8+ T cell accumulation. Overexpression/knockdown experiments, co-immunoprecipitation (NPRL2-TRIM16), ubiquitination assays, cuproptosis assays in CD8+ T cells, immunohistochemistry of clinical glioma specimens Cellular and molecular life sciences Medium 39367988
2016 GATOR1 components including NPRL2 are mutated in focal epilepsies associated with focal cortical dysplasia; brain tissue from patients with NPRL2 mutations shows hyperactivation of the mTORC1 pathway as measured by phospho-S6 immunoreactivity. Targeted sequencing of GATOR1/GATOR2 genes, phospho-S6 immunohistochemistry in resected brain tissue Epilepsia Medium 27173016

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2013 A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science (New York, N.Y.) 884 23723238
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science (New York, N.Y.) 454 20947764
2000 The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer research 454 11085536
2017 Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature 438 29236692
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2014 The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell reports 353 25263562
2011 Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nature genetics 348 21822266
2017 KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1. Nature 270 28199306
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2018 The landscape of epilepsy-related GATOR1 variants. Genetics in medicine : official journal of the American College of Medical Genetics 183 30093711
2015 Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy. Annals of neurology 176 26505888
2019 Structural basis for the docking of mTORC1 on the lysosomal surface. Science (New York, N.Y.) 166 31601708
2017 SZT2 dictates GATOR control of mTORC1 signalling. Nature 159 28199315
2018 Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes. Nature 158 29590090
2020 A Cellular Mechanism to Detect and Alleviate Reductive Stress. Cell 156 32941802
1991 Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini. Molecular and cellular biology 156 1922062
2012 Translational homeostasis via the mRNA cap-binding protein, eIF4E. Molecular cell 151 22578813
2002 Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo. Cancer research 147 11980673
2016 Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia. Epilepsia 140 27173016
2005 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature. The Journal of clinical endocrinology and metabolism 132 16384845
2011 Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology 130 21914782
2009 A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex. PLoS genetics 126 19521502
2019 Architecture of human Rag GTPase heterodimers and their complex with mTORC1. Science (New York, N.Y.) 117 31601764
2007 Toward a confocal subcellular atlas of the human proteome. Molecular & cellular proteomics : MCP 114 18029348
2012 Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes. Developmental biology 112 22546688
2005 A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn/cn mouse. The Journal of biological chemistry 110 15722353
2013 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature in patients initially classified as idiopathic short stature. The Journal of clinical endocrinology and metabolism 108 24001744
2015 The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation. Molecular cell 104 25936802
2014 Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes. Development (Cambridge, England) 88 25183874
2015 Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature. Human mutation 79 25703509
2011 Selective regulation of autophagy by the Iml1-Npr2-Npr3 complex in the absence of nitrogen starvation. Molecular biology of the cell 78 21900499
2012 CNP/NPR2 signaling maintains oocyte meiotic arrest in early antral follicles and is suppressed by EGFR-mediated signaling in preovulatory follicles. Molecular reproduction and development 75 22987720
2013 Overgrowth syndrome associated with a gain-of-function mutation of the natriuretic peptide receptor 2 (NPR2) gene. American journal of medical genetics. Part A 70 24259409
2007 The receptor guanylyl cyclase Npr2 is essential for sensory axon bifurcation within the spinal cord. The Journal of cell biology 66 17954614
2014 Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature. The Journal of clinical endocrinology and metabolism 64 24471569
2004 Functional characterization of the candidate tumor suppressor gene NPRL2/G21 located in 3p21.3C. Cancer research 62 15374952
2014 Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3 inactivates TORC1 and induces autophagy. Autophagy 61 25046117
2006 The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells. Cancer research 60 17018626
2015 Heterozygous NPR2 Mutations Cause Disproportionate Short Stature, Similar to Léri-Weill Dyschondrosteosis. The Journal of clinical endocrinology and metabolism 59 26075495
2019 Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the Rag GTPases. The Journal of biological chemistry 54 30651352
2013 Epidermal growth factor receptor signaling-dependent calcium elevation in cumulus cells is required for NPR2 inhibition and meiotic resumption in mouse oocytes. Endocrinology 54 23787120
2012 A novel loss-of-function mutation in Npr2 clarifies primary role in female reproduction and reveals a potential therapy for acromesomelic dysplasia, Maroteaux type. Human molecular genetics 54 23065701
2014 The TORC1 inhibitors Nprl2 and Nprl3 mediate an adaptive response to amino-acid starvation in Drosophila. Cell death and differentiation 45 24786828
2010 Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer. BMC cancer 44 20193080
2016 Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype. Sleep 43 26888452
2015 Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone. Developmental biology 43 26522847
2012 NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary. Reproduction (Cambridge, England) 43 22696190
2018 NPRL2 enhances autophagy and the resistance to Everolimus in castration-resistant prostate cancer. The Prostate 41 30178500
2015 Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2. Cell reports 40 26166573
2017 Natriuretic peptide receptor 2 (NPR2) localized in bovine oocyte underlies a unique mechanism for C-type natriuretic peptide (CNP)-induced meiotic arrest. Theriogenology 39 29080478
2014 Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites. Science signaling 39 25515537
2003 Anticancer drug resistance induced by disruption of the Saccharomyces cerevisiae NPR2 gene: a novel component involved in cisplatin- and doxorubicin-provoked cell kill. Molecular pharmacology 38 12869630
2021 Mechanism of quercetin on the improvement of ovulation disorder and regulation of ovarian CNP/NPR2 in PCOS model rats. Journal of the Formosan Medical Association = Taiwan yi zhi 37 34538551
2014 Bifurcation of axons from cranial sensory neurons is disabled in the absence of Npr2-induced cGMP signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 24431432
2020 NPR2 Variants Are Frequent among Children with Familiar Short Stature and Respond Well to Growth Hormone Therapy. The Journal of clinical endocrinology and metabolism 34 31990356
2010 NPRL2 sensitizes human non-small cell lung cancer (NSCLC) cells to cisplatin treatment by regulating key components in the DNA repair pathway. PloS one 33 20700484
2007 Short-limbed dwarfism: slw is a new allele of Npr2 causing chondrodysplasia. The Journal of heredity 32 17728275
2017 Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor. eLife 28 29199951
2014 TUSC4 functions as a tumor suppressor by regulating BRCA1 stability. Cancer research 28 25480944
2008 TUSC4/NPRL2, a novel PDK1-interacting protein, inhibits PDK1 tyrosine phosphorylation and its downstream signaling. Cancer science 27 18616680
2014 Mutation of Npr2 leads to blurred tonotopic organization of central auditory circuits in mice. PLoS genetics 26 25473838
2008 [Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer]. Molekuliarnaia biologiia 25 19140316
2015 Acromesomelic dysplasia, type maroteaux caused by novel loss-of-function mutations of the NPR2 gene: Three case reports. American journal of medical genetics. Part A 23 26567084
2014 Epidermal growth factor-network signaling mediates luteinizing hormone regulation of BNP and CNP and their receptor NPR2 during porcine oocyte meiotic resumption. Molecular reproduction and development 23 25348585
2019 Npr2 null mutants show initial overshooting followed by reduction of spiral ganglion axon projections combined with near-normal cochleotopic projection. Cell and tissue research 22 31201541
2021 Clinical Characteristics of Short-Stature Patients With an NPR2 Mutation and the Therapeutic Response to rhGH. The Journal of clinical endocrinology and metabolism 21 33205215
2020 Role of NPR2 mutation in idiopathic short stature: Identification of two novel mutations. Molecular genetics & genomic medicine 21 31960617
2020 NPRL2 promotes docetaxel chemoresistance in castration resistant prostate cancer cells by regulating autophagy through the mTOR pathway. Experimental cell research 20 32234375
2020 Can extracellular vesicles from bovine ovarian follicular fluid modulate the in-vitro oocyte meiosis progression similarly to the CNP-NPR2 system? Theriogenology 20 32814248
2010 Npr2, yeast homolog of the human tumor suppressor NPRL2, is a target of Grr1 required for adaptation to growth on diverse nitrogen sources. Eukaryotic cell 20 20154027
2022 Dorsal telencephalon-specific Nprl2- and Nprl3-knockout mice: novel mouse models for GATORopathy. Human molecular genetics 19 34965576
2017 Tumor suppressor NPRL2 induces ROS production and DNA damage response. Scientific reports 19 29127423
2020 Short Stature is Progressive in Patients with Heterozygous NPR2 Mutations. The Journal of clinical endocrinology and metabolism 17 32720985
2018 Molecular and in silico analyses validates pathogenicity of homozygous mutations in the NPR2 gene underlying variable phenotypes of Acromesomelic dysplasia, type Maroteaux. The international journal of biochemistry & cell biology 17 30016695
2015 Homozygous sequence variants in the NPR2 gene underlying Acromesomelic dysplasia Maroteaux type (AMDM) in consanguineous families. Annals of human genetics 17 25959430
2018 Regulation of the Natriuretic Peptide Receptor 2 (Npr2) by Phosphorylation of Juxtamembrane Serine and Threonine Residues Is Essential for Bifurcation of Sensory Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 30249793
2017 Long-term response to growth hormone therapy in a patient with short stature caused by a novel heterozygous mutation in NPR2. Journal of pediatric endocrinology & metabolism : JPEM 15 27941173
2015 Functional mechanism of the enhancement of 5-fluorouracil sensitivity by TUSC4 in colon cancer cells. Oncology letters 15 26788191
2021 Sgpl1 deletion elevates S1P levels, contributing to NPR2 inactivity and p21 expression that block germ cell development. Cell death & disease 14 34083520
2021 FOXO1 inhibits prostate cancer cell proliferation via suppressing E2F1 activated NPRL2 expression. Cell biology international 14 34459063
2014 Decreased expression of NPRL2 in renal cancer cells is associated with unfavourable pathological, proliferation and apoptotic features. Pathology oncology research : POR 14 24789683
2018 Loss of Axon Bifurcation in Mesencephalic Trigeminal Neurons Impairs the Maximal Biting Force in Npr2-Deficient Mice. Frontiers in cellular neuroscience 13 29962937
2012 Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide. Endocrine-related cancer 13 22645228
2022 Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type. Frontiers in genetics 12 35368703
2022 Heterozygous NPR2 Variants in Idiopathic Short Stature. Genes 12 35741827
2019 The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila. Aging 12 31712450
2016 NPR2 is involved in FSH-mediated mouse oocyte meiotic resumption. Journal of ovarian research 12 26880031
2014 Relationship between tumor and peripheral blood NPRL2 mRNA levels in patients with colorectal adenoma and colorectal cancer. Cancer biology & therapy 11 24521741
2018 Targeting NPRL2 to enhance the efficacy of Olaparib in castration-resistant prostate cancer. Biochemical and biophysical research communications 10 30522863
2024 Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase†. Biology of reproduction 9 37774352
2022 NPRL2 Inhibition of mTORC1 Controls Sodium Channel Expression and Brain Amino Acid Homeostasis. eNeuro 9 35165201
2021 A splicing variation in NPRL2 causing familial focal epilepsy with variable foci: additional cases and literature review. Journal of human genetics 9 34376795
2021 NPR2 gene variants in familial short stature: a single-center study. Journal of pediatric endocrinology & metabolism : JPEM 9 34565054
2018 Heterozygous NPR2 Mutation in Two Family Members with Short Stature and Skeletal Dysplasia. Case reports in endocrinology 9 30622824
2016 The Loss of Lam2 and Npr2-Npr3 Diminishes the Vacuolar Localization of Gtr1-Gtr2 and Disinhibits TORC1 Activity in Fission Yeast. PloS one 9 27227887
2016 Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats. Molecular and cellular endocrinology 9 27283501
2015 Amino acid-dependent NPRL2 interaction with Raptor determines mTOR Complex 1 activation. Cellular signalling 9 26582740
2023 Unveiling the pathogenic mechanisms of NPR2 missense variants: insights into the genotype-associated severity in acromesomelic dysplasia and short stature. Frontiers in cell and developmental biology 8 38078000
2022 Novel NPR2 Gene Mutations Affect Chondrocytes Function via ER Stress in Short Stature. Cells 8 35455946
2022 LncRNA-ANAPC2 and lncRNA-NEFM positively regulates the inflammatory response via the miR-451/npr2/ hdac8 axis in grass carp. Fish & shellfish immunology 8 35843524
2022 NPRL2 down-regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression. Hepatology communications 8 36321403
2021 Phenotypic and Genotypic Characterization of NPRL2-Related Epilepsy: Two Case Reports and Literature Review. Frontiers in neurology 8 34912289
2020 A novel nonsense mutation in NPR2 gene causing Acromesomelic dysplasia, type Maroteaux in a consanguineous family in Southern Punjab (Pakistan). Genes & genomics 8 32506268
2023 Novel pathogenic NPR2 variants in short stature patients and the therapeutic response to rhGH. Orphanet journal of rare diseases 7 37501190
2021 G protein-coupled estrogen receptor signaling dependent epidermal growth-like factor expression is required for NPR2 inhibition and meiotic resumption in goat oocytes. Theriogenology 7 34571396
2019 Nppc/Npr2/cGMP signaling cascade maintains oocyte developmental capacity. Cellular and molecular biology (Noisy-le-Grand, France) 7 31078160
2018 Overexpression of Nitrogen Permease Regulator Like-2 (NPRL2) Enhances Sensitivity to Irinotecan (CPT-11) in Colon Cancer Cells by Activating the DNA Damage Checkpoint Pathway. Medical science monitor : international medical journal of experimental and clinical research 7 29519997
2025 NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model. eLife 6 39932765
2022 Increased glycine contributes to synaptic dysfunction and early mortality in Nprl2 seizure model. iScience 6 35602938
2021 NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation. Experimental cell research 6 33905671
2017 Suppression of Npr1, not Npr2 gene function induces hypertrophic growth in H9c2 cells in vitro. Biochemical and biophysical research communications 6 28743500
2014 Porcine natriuretic peptide type B (pNPPB) maintains mouse oocyte meiotic arrest via natriuretic peptide receptor 2 (NPR2) in cumulus cells. Molecular reproduction and development 6 24615855
2024 NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8+T lymphocyte cuproptosis in glioma. Cellular and molecular life sciences : CMLS 5 39367988
2020 Defective development and microcirculation of intestine in Npr2 mutant mice. Scientific reports 5 32901096
2019 Expression and localization of Npr2 in mouse oocytes and pre-implantation embryos. Biotechnic & histochemistry : official publication of the Biological Stain Commission 5 30729815
2020 A novel NPR2 mutation (p.Arg388Gln) in a patient with acromesomelic dysplasia, type Maroteaux. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 4 32694885
2015 A NOVEL MUTATION IN NPR2 GENE IN A PATIENT WITH ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE. Genetic counseling (Geneva, Switzerland) 4 26349192
2023 Clinical phenotype and genotype of NPRL2-related epilepsy: Four cases reports and literature review. Seizure 3 37741786
2020 Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation. Journal of pediatric endocrinology & metabolism : JPEM 3 31927522
2016 Biological characteristics of renal cancer cells after CTP-mediated cancer suppressor gene NPRL2 protein treatment. Biological chemistry 3 27186678