{"gene":"NPY5R","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":2013,"finding":"NPY5R localizes to neuronal primary cilia in hypothalamic neurons via the Bardet-Biedl syndrome (BBS) pathway; BBS mutant mice fail to localize NPY2R/NPY5R to cilia and fail to activate c-fos or decrease food intake in response to PYY3-36, demonstrating that ciliary targeting of NPY receptors is required for normal energy balance signaling.","method":"Comprehensive GPCR localization screen, mouse models of BBS and obese tubby mice, c-fos activation assay, food intake measurement, cAMP signaling assay in ciliary vs. non-ciliary cells","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (localization screen, genetic mouse models, signaling assays, behavioral readouts) in a single study with clear functional consequences","pmids":["24316073"],"is_preprint":false},{"year":2021,"finding":"NPY5R in the paraventricular thalamus mediates hunger-dependent food-odour attraction; mice lacking NPY5R fail to prefer food odours over pheromones after fasting, and acute NPY injection rescues this preference, indicating NPY acts through NPY5R to read olfactory circuits during behavioural expression.","method":"Npy5r knockout mice, optogenetic AGRP neuron activation, cell-specific NPY rescue, acute NPY injection, olfactory behavioural assays","journal":"Nature","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function with specific behavioural phenotype, optogenetic circuit dissection, and acute pharmacological rescue across multiple orthogonal approaches","pmids":["33658716"],"is_preprint":false},{"year":2019,"finding":"Oxytocin-induced upregulation of NPY5R protein in the paraventricular nucleus (PVN) is required for oxytocin's anxiolytic effect; NPY5R agonist infusion into the PVN reduces anxiety-like behaviour, and NPY5R antagonist pretreatment blocks oxytocin-induced anxiolysis. The mechanism involves oxytocin activating PKC-dependent eEF2 phosphorylation leading to de novo NPY5R protein synthesis.","method":"In vivo PVN infusion of NPY5R agonist/antagonist, hypothalamic cell line experiments, protein synthesis inhibition, eEF2 activation assays, anxiety behavioural tests in male rats","journal":"Biological psychiatry","confidence":"High","confidence_rationale":"Tier 2 — in vivo pharmacological gain/loss-of-function with defined molecular mechanism (eEF2/PKC pathway) and specific behavioural readout, multiple orthogonal methods","pmids":["30826070"],"is_preprint":false},{"year":2003,"finding":"Chronic intracerebroventricular NPY infusion stimulates food intake and induces obesity in wild-type mice; the lack of either Npy1r or Npy5r alone does not prevent this feeding response, indicating biological redundancy between Y1 and Y5 receptor signaling in NPY-mediated control of food intake.","method":"Npy1r and Npy5r knockout mice, chronic lateral ventricle NPY infusion, food intake measurement, fat pad weight, plasma hormone levels, hypothalamic gene expression","journal":"Endocrinology","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis using knockout mice with quantitative physiological and molecular readouts","pmids":["14525913"],"is_preprint":false},{"year":2022,"finding":"NPY5R mRNA abundance is induced by hypoxia in a hypoxia-inducible factor (HIF)-dependent manner in breast cancer cells; HIFs bind genomic regions upstream of NPY5R transcription start sites, and NPY5R-stimulated MAPK/ERK signaling is more rapidly activated in hypoxic cells and is IGF1R-independent under hypoxia, rendering hypoxic cells more sensitive to NPY stimulation.","method":"ChIP for HIF binding at NPY5R promoter regions, MAPK/ERK signaling assays in normoxic vs. hypoxic cells, NPY5R agonist stimulation, IGF1R inhibitor experiments, cell proliferation and migration assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — ChIP demonstrating direct HIF binding to NPY5R locus plus functional signaling assays with multiple orthogonal methods","pmids":["35093384"],"is_preprint":false},{"year":2022,"finding":"NPY5R activation promotes hepatic ApoA1 synthesis and secretion through ERK1/2 and PKA signal transduction pathways; NPY5R inhibition blocks NPY-induced ApoA1 upregulation and NPY5R agonist stimulates ApoA1 expression and secretion in hepatocytes in vitro and in vivo.","method":"In vivo NPY/NPY5R agonist injection in rodents, HepG2 and BRL-3A hepatocyte cultures with NPY receptor antagonists/agonists, ERK1/2 and PKA pathway inhibitors, ApoA1 protein and mRNA quantification","journal":"Peptides","confidence":"Medium","confidence_rationale":"Tier 2 — in vitro and in vivo receptor pharmacology with pathway inhibition, single lab study","pmids":["35660638"],"is_preprint":false},{"year":2020,"finding":"NPY directly suppresses neurokinin B-evoked firing of arcuate kisspeptin neurons through NPY1R (partially) but not NPY5R, as NPY5R antagonist L152,804 was ineffective while NPY1R antagonist BIBO 3304 partially blocked the suppression; this direct inhibitory effect was confirmed in the presence of tetrodotoxin, indicating post-synaptic direct action.","method":"Acute brain slice electrophysiology and calcium imaging in Kiss1-GFP and Kiss1-GCaMP6 mice, NPY1R and NPY5R selective antagonists, tetrodotoxin controls","journal":"Journal of neuroendocrinology","confidence":"Medium","confidence_rationale":"Tier 1 — direct ex vivo electrophysiology with pharmacological receptor discrimination; demonstrates NPY5R is not the mediator of NPY's direct effect on kisspeptin neurons","pmids":["32337804"],"is_preprint":false},{"year":2019,"finding":"NPY5R in the lateral hypothalamic area (LHA) mediates orexigenic effects of NPY on chow intake; NPY5R antagonism prevents intra-LHA NPY-induced feeding in both chow-fed and diet-induced obese (fcHFHS) rats, whereas NPY1R antagonism is effective only in chow-fed rats, indicating a diet-induced shift in LHA NPY receptor subtype dependence.","method":"Intra-LHA NPY infusion in chow vs. fcHFHS-fed rats, selective NPY1R and NPY5R antagonist co-administration, 2-hour food intake measurement with cross-over design","journal":"Neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 — site-specific pharmacological dissection of receptor subtype roles with defined dietary context and behavioural readout, single lab","pmids":["31887359"],"is_preprint":false},{"year":2020,"finding":"NPY5R mediates NPY-induced proliferation of early antral granulosa cells through the MEK signaling pathway; NPY5R antagonist (CGP71683) and MEK inhibitors (PD98059 and U0126) block NPY-induced Ki67-positive cell increase in early antral but not late antral follicles.","method":"Rat granulosa cell isolation from follicles at different stages, NPY treatment with NPY5R antagonist and MEK inhibitors, Ki67 proliferation assay, TUNEL apoptosis assay","journal":"Journal of ovarian research","confidence":"Medium","confidence_rationale":"Tier 2 — receptor pharmacology with pathway inhibitors and specific cellular phenotype readout, single lab","pmids":["31915051"],"is_preprint":false},{"year":2015,"finding":"NPY stimulates autophagy in rodent hypothalamus via NPY1R or NPY5R activation, involving concerted action of multiple signaling pathways; NPY also mediates caloric restriction-induced autophagy in hypothalamic neurons.","method":"Rodent hypothalamic neuron cultures, receptor subtype pharmacology, autophagy assays","journal":"Autophagy","confidence":"Low","confidence_rationale":"Tier 3 — review/commentary citing original work without full experimental detail in this abstract","pmids":["26086271"],"is_preprint":false},{"year":2008,"finding":"A selective Y5 receptor antagonist reduces body weight in diet-induced obese C57BL/6 mice but not in Npy5r knockout mice, confirming on-target specificity; the antagonist produced fat-selective body weight loss and ameliorated obesity-associated insulin resistance.","method":"Diet-induced obese C57BL/6 and Npy5r(-/-) mice, oral Y5 antagonist administration, body composition by NMR, insulin tolerance test, adipose tissue weights","journal":"Obesity (Silver Spring, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 — genetic and pharmacological confirmation of on-target mechanism with physiological readouts","pmids":["18421274"],"is_preprint":false},{"year":2023,"finding":"NPY5R antagonism in hypoxia more greatly reduces MAPK signaling, cell proliferation, cell migration, invasion, and spheroid growth in breast cancer cells; combined NPY1R and NPY5R antagonism has additive anti-tumor effects, and NPY5R protein levels in human breast tumor tissue correlate with advanced cancer.","method":"NPY1R and NPY5R antagonists in 2D and 3D breast cancer cell models (MDA-MB-231 and MCF7), MAPK signaling assays, migration, proliferation, invasion assays, immunofluorescence of human tumor tissue","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 — pharmacological receptor antagonism with multiple functional assays in normoxia and hypoxia, supported by human tissue data","pmids":["37264315"],"is_preprint":false},{"year":2025,"finding":"NPY5R is required for extrapulmonary metastasis of Ewing sarcoma; CRISPR/Cas9 knockout of NPY5R in SK-ES-1 xenografts eliminates metastases from NPY5R-null clones, and the underlying mechanism is NPY/Y5R-dependent RhoA activation driving cell motility via an autocrine NPY loop.","method":"Doxycycline-inducible CRISPR/Cas9 NPY5R knockout in xenografts, in vivo metastasis assays, in vitro cell motility assays, RhoA activation assays","journal":"Oncogene","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function (CRISPR KO) in vivo with mechanistic identification of RhoA pathway and autocrine loop, multiple orthogonal methods","pmids":["40676141"],"is_preprint":false},{"year":2022,"finding":"NPY2R forms a protein complex with NPY5R and NFATc1 in sebaceous glands; this complex is present at postnatal day 25 and is associated with DYRK1A-mediated NFATc1 phosphorylation (inactivation), while at PND-35 NFATc1 dephosphorylation and nuclear localization enables transcription of sebum-related genes.","method":"Immunoprecipitation, mass spectrometry, gel filtration, ChIP-seq for NFATc1, RNA sequencing, western blot, immunofluorescence","journal":"Cellular & molecular biology letters","confidence":"Medium","confidence_rationale":"Tier 2 — protein complex confirmed by Co-IP/MS with functional ChIP-seq and mechanistic follow-up, but focuses on NPY2R/NFATc1; NPY5R is a component of the complex","pmids":["37501148"],"is_preprint":false},{"year":2006,"finding":"Human NPY5R was stably expressed as a functional receptor using IRES-based bicistronic vectors; the receptor displayed pharmacological properties consistent with reported NPY5R characteristics, enabling establishment of a stable cell line expressing active human NPY5R.","method":"Bicistronic vector expression in cell lines, radioligand binding, functional receptor assays","journal":"Biochimie","confidence":"Low","confidence_rationale":"Tier 3 — technical/methodological paper confirming receptor functionality without deep mechanistic characterization","pmids":["16808994"],"is_preprint":false},{"year":2016,"finding":"NPY5R PET radiotracer [18F]LuAE00654 penetrates the blood-brain barrier in baboons and shows specific in vivo binding in the striatum (highest NPY5R binding region), with up to 60% displacement by a specific NPY5R antagonist in blocking studies.","method":"PET imaging in anesthetized baboons, blocking studies with selective NPY5R antagonist, plasma metabolism analysis","journal":"ACS chemical neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo pharmacological receptor occupancy confirmed by displacement with selective antagonist","pmids":["26886507"],"is_preprint":false}],"current_model":"NPY5R is a Gi/o-coupled GPCR that localizes to neuronal primary cilia via the BBS pathway to amplify cAMP signaling in response to NPY/PYY ligands, mediates hypothalamic control of feeding and energy homeostasis (with functional redundancy with NPY1R), drives hunger-dependent food-odour attraction through thalamic NPY release, underlies oxytocin-induced anxiolysis via PKC/eEF2-dependent de novo synthesis in the PVN, promotes cancer cell motility through RhoA activation in an autocrine NPY loop, activates hepatic ApoA1 synthesis via ERK1/2 and PKA, and stimulates granulosa cell proliferation through the MEK pathway."},"narrative":{"teleology":[{"year":2003,"claim":"Determining whether NPY5R is individually required for NPY-driven feeding revealed functional redundancy with NPY1R, establishing that central orexigenic signaling does not depend on a single receptor subtype.","evidence":"Chronic ICV NPY infusion in Npy1r and Npy5r single-knockout mice with food intake and metabolic readouts","pmids":["14525913"],"confidence":"High","gaps":["Double Npy1r/Npy5r knockout not tested","Downstream signaling pathways mediating feeding not dissected","Contribution of other NPY receptor subtypes not excluded"]},{"year":2008,"claim":"Pharmacological blockade of NPY5R in obese mice produced fat-selective weight loss confirmed on-target by Npy5r knockout controls, establishing NPY5R as a therapeutically relevant mediator of diet-induced obesity.","evidence":"Oral Y5 antagonist in diet-induced obese C57BL/6 vs. Npy5r−/− mice with body composition NMR and insulin tolerance tests","pmids":["18421274"],"confidence":"Medium","gaps":["Mechanism of fat-selective weight loss not identified","Long-term efficacy and compensatory receptor upregulation not assessed"]},{"year":2013,"claim":"Demonstrating that NPY5R localizes to neuronal primary cilia via BBS-dependent trafficking linked ciliopathy-associated obesity to defective neuropeptide receptor signaling, showing that ciliary localization is required for PYY3-36-mediated satiety responses.","evidence":"GPCR localization screen, BBS and tubby mutant mouse models, c-fos activation, food intake, and cAMP signaling assays in ciliated vs. non-ciliated cells","pmids":["24316073"],"confidence":"High","gaps":["Whether NPY5R signals exclusively from cilia or also from the plasma membrane not resolved","Structural basis of BBS-mediated ciliary targeting of NPY5R unknown"]},{"year":2016,"claim":"Development of a brain-penetrant PET radiotracer with specific striatal binding demonstrated that NPY5R is expressed and pharmacologically accessible in vivo in primate brain, enabling future occupancy studies.","evidence":"PET imaging in baboons with [18F]LuAE00654 and displacement by selective NPY5R antagonist","pmids":["26886507"],"confidence":"Medium","gaps":["Regional receptor density quantification not performed","Translation to human imaging not yet demonstrated"]},{"year":2019,"claim":"Two studies revealed region-specific NPY5R roles: in the PVN, oxytocin drives de novo NPY5R synthesis via PKC/eEF2 to mediate anxiolysis; in the LHA, NPY5R becomes the dominant orexigenic receptor under high-fat diet conditions, resolving how diet alters NPY receptor subtype dependence.","evidence":"Intra-PVN agonist/antagonist infusion with eEF2/PKC pathway dissection and anxiety tests in rats; intra-LHA NPY infusion with subtype-selective antagonists in chow vs. high-fat-fed rats","pmids":["30826070","31887359"],"confidence":"High","gaps":["Whether eEF2-dependent NPY5R synthesis occurs in other brain regions unknown","Molecular basis of diet-induced receptor subtype switching in LHA not identified"]},{"year":2020,"claim":"Electrophysiological dissection showed that NPY's direct inhibition of arcuate kisspeptin neurons is mediated by NPY1R, not NPY5R, delineating receptor subtype specificity in reproductive neuroendocrine circuits.","evidence":"Acute brain slice electrophysiology and calcium imaging in Kiss1-reporter mice with selective NPY1R/NPY5R antagonists and tetrodotoxin","pmids":["32337804"],"confidence":"Medium","gaps":["Indirect NPY5R effects via presynaptic or network mechanisms not excluded","Only one hypothalamic cell type tested"]},{"year":2021,"claim":"Circuit-level dissection established that NPY5R in the paraventricular thalamus is the specific receptor required for hunger-state-dependent switching of olfactory valence, connecting metabolic state to sensory preference.","evidence":"Npy5r knockout mice, optogenetic AGRP neuron activation, cell-specific NPY rescue, and olfactory behavioral assays","pmids":["33658716"],"confidence":"High","gaps":["Downstream intracellular signaling in thalamic neurons not characterized","Whether NPY5R modulates other sensory modalities unknown"]},{"year":2022,"claim":"Multiple studies defined peripheral NPY5R signaling: HIF-dependent transcriptional upregulation sensitizes breast cancer cells to NPY-driven MAPK/ERK signaling under hypoxia; NPY5R activates ERK1/2 and PKA to stimulate hepatic ApoA1 synthesis; and NPY5R forms a complex with NPY2R and NFATc1 in sebaceous glands linked to sebum gene regulation.","evidence":"ChIP for HIF at NPY5R locus plus MAPK assays in hypoxic breast cancer cells; hepatocyte cultures and rodent ApoA1 assays with pathway inhibitors; Co-IP/MS and ChIP-seq in sebaceous glands","pmids":["35093384","35660638","37501148"],"confidence":"Medium","gaps":["Whether HIF-NPY5R axis operates in non-breast cancers not tested","ApoA1 regulation confirmed in cell lines and rodents but not in human hepatocytes","Functional consequence of NPY2R-NPY5R-NFATc1 complex for NPY5R signaling not determined"]},{"year":2023,"claim":"Pharmacological NPY5R blockade under hypoxia showed enhanced anti-proliferative and anti-migratory effects in breast cancer models, and combined NPY1R/NPY5R antagonism was additive, establishing NPY5R as a hypoxia-responsive oncogenic signaling node.","evidence":"NPY1R/NPY5R antagonists in 2D/3D breast cancer models with MAPK, migration, invasion, and spheroid assays; immunofluorescence of human breast tumor tissue","pmids":["37264315"],"confidence":"Medium","gaps":["No in vivo tumor model with NPY5R antagonism","Correlation of NPY5R levels with patient outcome not established causally"]},{"year":2025,"claim":"CRISPR knockout of NPY5R in Ewing sarcoma xenografts eliminated extrapulmonary metastasis and identified RhoA activation via an autocrine NPY loop as the pro-metastatic mechanism, establishing a direct requirement for NPY5R in tumor dissemination.","evidence":"Inducible CRISPR/Cas9 NPY5R KO in SK-ES-1 xenografts, in vivo metastasis assays, RhoA activation assays, motility assays","pmids":["40676141"],"confidence":"High","gaps":["Whether RhoA activation is direct or through intermediate effectors not resolved","Generalizability to other sarcoma or cancer types not tested"]},{"year":null,"claim":"The structural basis of NPY5R coupling to divergent downstream effectors (Gi/o, MAPK/ERK, PKA, RhoA) in different cell types, and whether these reflect biased agonism or cell-context-dependent signaling complexes, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No cryo-EM or crystal structure of NPY5R","No systematic comparison of G-protein vs. arrestin coupling","Mechanism by which ciliary vs. plasma membrane localization shapes signaling output unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1,2,3,7]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,14]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,2,4,5,8,12]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[1,2,6,7]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[4,11,12]}],"complexes":["NPY2R-NPY5R-NFATc1 complex"],"partners":["NPY2R","NFATC1","DYRK1A","RHOA"],"other_free_text":[]},"mechanistic_narrative":"NPY5R is a Gi/o-coupled receptor for neuropeptide Y (NPY) and peptide YY (PYY) that functions as a central regulator of energy homeostasis, feeding behavior, and emotional state, while also mediating peripheral proliferative and metabolic signaling. In the hypothalamus, NPY5R localizes to neuronal primary cilia via the Bardet-Biedl syndrome (BBS) trafficking pathway, and this ciliary targeting is required for normal anorexigenic responses to PYY3-36; NPY5R exhibits functional redundancy with NPY1R in central orexigenic signaling, though in the lateral hypothalamic area it becomes the dominant orexigenic receptor subtype under high-fat diet conditions [PMID:24316073, PMID:14525913, PMID:31887359]. Beyond feeding, NPY5R in the paraventricular thalamus mediates hunger-state-dependent food-odour preference, and oxytocin-driven de novo synthesis of NPY5R via PKC/eEF2 signaling in the paraventricular nucleus is required for anxiolysis [PMID:33658716, PMID:30826070]. In peripheral tissues, NPY5R couples to MAPK/ERK, PKA, and RhoA pathways to drive hepatic ApoA1 synthesis, granulosa cell proliferation, and cancer cell motility and metastasis—the latter through an autocrine NPY loop that is amplified under hypoxia via HIF-dependent transcriptional upregulation of NPY5R [PMID:35660638, PMID:31915051, PMID:40676141, PMID:35093384]."},"prefetch_data":{"uniprot":{"accession":"Q15761","full_name":"Neuropeptide Y receptor type 5","aliases":["NPY-Y5 receptor","NPYY5-R","Y5 receptor"],"length_aa":445,"mass_kda":50.7,"function":"Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q15761/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NPY5R","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NPY5R","total_profiled":1310},"omim":[{"mim_id":"602001","title":"NEUROPEPTIDE Y RECEPTOR Y5; NPY5R","url":"https://www.omim.org/entry/602001"},{"mim_id":"601790","title":"PANCREATIC POLYPEPTIDE RECEPTOR 1; PPYR1","url":"https://www.omim.org/entry/601790"},{"mim_id":"162641","title":"NEUROPEPTIDE Y RECEPTOR Y1; NPY1R","url":"https://www.omim.org/entry/162641"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"adipose tissue","ntpm":6.7},{"tissue":"lymphoid tissue","ntpm":8.3}],"url":"https://www.proteinatlas.org/search/NPY5R"},"hgnc":{"alias_symbol":["NPYR5"],"prev_symbol":[]},"alphafold":{"accession":"Q15761","domains":[{"cath_id":"1.20.1070.10","chopping":"35-259_342-445","consensus_level":"medium","plddt":86.8495,"start":35,"end":445}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15761","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15761-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15761-F1-predicted_aligned_error_v6.png","plddt_mean":75.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NPY5R","jax_strain_url":"https://www.jax.org/strain/search?query=NPY5R"},"sequence":{"accession":"Q15761","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15761.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15761/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15761"}},"corpus_meta":[{"pmid":"24316073","id":"PMC_24316073","title":"Neuropeptide Y family 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obese tubby mice, c-fos activation assay, food intake measurement, cAMP signaling assay in ciliary vs. non-ciliary cells\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (localization screen, genetic mouse models, signaling assays, behavioral readouts) in a single study with clear functional consequences\",\n      \"pmids\": [\"24316073\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NPY5R in the paraventricular thalamus mediates hunger-dependent food-odour attraction; mice lacking NPY5R fail to prefer food odours over pheromones after fasting, and acute NPY injection rescues this preference, indicating NPY acts through NPY5R to read olfactory circuits during behavioural expression.\",\n      \"method\": \"Npy5r knockout mice, optogenetic AGRP neuron activation, cell-specific NPY rescue, acute NPY injection, olfactory behavioural assays\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function with specific behavioural phenotype, optogenetic circuit dissection, and acute pharmacological rescue across multiple orthogonal approaches\",\n      \"pmids\": [\"33658716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Oxytocin-induced upregulation of NPY5R protein in the paraventricular nucleus (PVN) is required for oxytocin's anxiolytic effect; NPY5R agonist infusion into the PVN reduces anxiety-like behaviour, and NPY5R antagonist pretreatment blocks oxytocin-induced anxiolysis. The mechanism involves oxytocin activating PKC-dependent eEF2 phosphorylation leading to de novo NPY5R protein synthesis.\",\n      \"method\": \"In vivo PVN infusion of NPY5R agonist/antagonist, hypothalamic cell line experiments, protein synthesis inhibition, eEF2 activation assays, anxiety behavioural tests in male rats\",\n      \"journal\": \"Biological psychiatry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo pharmacological gain/loss-of-function with defined molecular mechanism (eEF2/PKC pathway) and specific behavioural readout, multiple orthogonal methods\",\n      \"pmids\": [\"30826070\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Chronic intracerebroventricular NPY infusion stimulates food intake and induces obesity in wild-type mice; the lack of either Npy1r or Npy5r alone does not prevent this feeding response, indicating biological redundancy between Y1 and Y5 receptor signaling in NPY-mediated control of food intake.\",\n      \"method\": \"Npy1r and Npy5r knockout mice, chronic lateral ventricle NPY infusion, food intake measurement, fat pad weight, plasma hormone levels, hypothalamic gene expression\",\n      \"journal\": \"Endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis using knockout mice with quantitative physiological and molecular readouts\",\n      \"pmids\": [\"14525913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NPY5R mRNA abundance is induced by hypoxia in a hypoxia-inducible factor (HIF)-dependent manner in breast cancer cells; HIFs bind genomic regions upstream of NPY5R transcription start sites, and NPY5R-stimulated MAPK/ERK signaling is more rapidly activated in hypoxic cells and is IGF1R-independent under hypoxia, rendering hypoxic cells more sensitive to NPY stimulation.\",\n      \"method\": \"ChIP for HIF binding at NPY5R promoter regions, MAPK/ERK signaling assays in normoxic vs. hypoxic cells, NPY5R agonist stimulation, IGF1R inhibitor experiments, cell proliferation and migration assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — ChIP demonstrating direct HIF binding to NPY5R locus plus functional signaling assays with multiple orthogonal methods\",\n      \"pmids\": [\"35093384\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NPY5R activation promotes hepatic ApoA1 synthesis and secretion through ERK1/2 and PKA signal transduction pathways; NPY5R inhibition blocks NPY-induced ApoA1 upregulation and NPY5R agonist stimulates ApoA1 expression and secretion in hepatocytes in vitro and in vivo.\",\n      \"method\": \"In vivo NPY/NPY5R agonist injection in rodents, HepG2 and BRL-3A hepatocyte cultures with NPY receptor antagonists/agonists, ERK1/2 and PKA pathway inhibitors, ApoA1 protein and mRNA quantification\",\n      \"journal\": \"Peptides\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vitro and in vivo receptor pharmacology with pathway inhibition, single lab study\",\n      \"pmids\": [\"35660638\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NPY directly suppresses neurokinin B-evoked firing of arcuate kisspeptin neurons through NPY1R (partially) but not NPY5R, as NPY5R antagonist L152,804 was ineffective while NPY1R antagonist BIBO 3304 partially blocked the suppression; this direct inhibitory effect was confirmed in the presence of tetrodotoxin, indicating post-synaptic direct action.\",\n      \"method\": \"Acute brain slice electrophysiology and calcium imaging in Kiss1-GFP and Kiss1-GCaMP6 mice, NPY1R and NPY5R selective antagonists, tetrodotoxin controls\",\n      \"journal\": \"Journal of neuroendocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — direct ex vivo electrophysiology with pharmacological receptor discrimination; demonstrates NPY5R is not the mediator of NPY's direct effect on kisspeptin neurons\",\n      \"pmids\": [\"32337804\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"NPY5R in the lateral hypothalamic area (LHA) mediates orexigenic effects of NPY on chow intake; NPY5R antagonism prevents intra-LHA NPY-induced feeding in both chow-fed and diet-induced obese (fcHFHS) rats, whereas NPY1R antagonism is effective only in chow-fed rats, indicating a diet-induced shift in LHA NPY receptor subtype dependence.\",\n      \"method\": \"Intra-LHA NPY infusion in chow vs. fcHFHS-fed rats, selective NPY1R and NPY5R antagonist co-administration, 2-hour food intake measurement with cross-over design\",\n      \"journal\": \"Neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — site-specific pharmacological dissection of receptor subtype roles with defined dietary context and behavioural readout, single lab\",\n      \"pmids\": [\"31887359\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"NPY5R mediates NPY-induced proliferation of early antral granulosa cells through the MEK signaling pathway; NPY5R antagonist (CGP71683) and MEK inhibitors (PD98059 and U0126) block NPY-induced Ki67-positive cell increase in early antral but not late antral follicles.\",\n      \"method\": \"Rat granulosa cell isolation from follicles at different stages, NPY treatment with NPY5R antagonist and MEK inhibitors, Ki67 proliferation assay, TUNEL apoptosis assay\",\n      \"journal\": \"Journal of ovarian research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — receptor pharmacology with pathway inhibitors and specific cellular phenotype readout, single lab\",\n      \"pmids\": [\"31915051\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"NPY stimulates autophagy in rodent hypothalamus via NPY1R or NPY5R activation, involving concerted action of multiple signaling pathways; NPY also mediates caloric restriction-induced autophagy in hypothalamic neurons.\",\n      \"method\": \"Rodent hypothalamic neuron cultures, receptor subtype pharmacology, autophagy assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — review/commentary citing original work without full experimental detail in this abstract\",\n      \"pmids\": [\"26086271\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"A selective Y5 receptor antagonist reduces body weight in diet-induced obese C57BL/6 mice but not in Npy5r knockout mice, confirming on-target specificity; the antagonist produced fat-selective body weight loss and ameliorated obesity-associated insulin resistance.\",\n      \"method\": \"Diet-induced obese C57BL/6 and Npy5r(-/-) mice, oral Y5 antagonist administration, body composition by NMR, insulin tolerance test, adipose tissue weights\",\n      \"journal\": \"Obesity (Silver Spring, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic and pharmacological confirmation of on-target mechanism with physiological readouts\",\n      \"pmids\": [\"18421274\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NPY5R antagonism in hypoxia more greatly reduces MAPK signaling, cell proliferation, cell migration, invasion, and spheroid growth in breast cancer cells; combined NPY1R and NPY5R antagonism has additive anti-tumor effects, and NPY5R protein levels in human breast tumor tissue correlate with advanced cancer.\",\n      \"method\": \"NPY1R and NPY5R antagonists in 2D and 3D breast cancer cell models (MDA-MB-231 and MCF7), MAPK signaling assays, migration, proliferation, invasion assays, immunofluorescence of human tumor tissue\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pharmacological receptor antagonism with multiple functional assays in normoxia and hypoxia, supported by human tissue data\",\n      \"pmids\": [\"37264315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NPY5R is required for extrapulmonary metastasis of Ewing sarcoma; CRISPR/Cas9 knockout of NPY5R in SK-ES-1 xenografts eliminates metastases from NPY5R-null clones, and the underlying mechanism is NPY/Y5R-dependent RhoA activation driving cell motility via an autocrine NPY loop.\",\n      \"method\": \"Doxycycline-inducible CRISPR/Cas9 NPY5R knockout in xenografts, in vivo metastasis assays, in vitro cell motility assays, RhoA activation assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function (CRISPR KO) in vivo with mechanistic identification of RhoA pathway and autocrine loop, multiple orthogonal methods\",\n      \"pmids\": [\"40676141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NPY2R forms a protein complex with NPY5R and NFATc1 in sebaceous glands; this complex is present at postnatal day 25 and is associated with DYRK1A-mediated NFATc1 phosphorylation (inactivation), while at PND-35 NFATc1 dephosphorylation and nuclear localization enables transcription of sebum-related genes.\",\n      \"method\": \"Immunoprecipitation, mass spectrometry, gel filtration, ChIP-seq for NFATc1, RNA sequencing, western blot, immunofluorescence\",\n      \"journal\": \"Cellular & molecular biology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — protein complex confirmed by Co-IP/MS with functional ChIP-seq and mechanistic follow-up, but focuses on NPY2R/NFATc1; NPY5R is a component of the complex\",\n      \"pmids\": [\"37501148\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Human NPY5R was stably expressed as a functional receptor using IRES-based bicistronic vectors; the receptor displayed pharmacological properties consistent with reported NPY5R characteristics, enabling establishment of a stable cell line expressing active human NPY5R.\",\n      \"method\": \"Bicistronic vector expression in cell lines, radioligand binding, functional receptor assays\",\n      \"journal\": \"Biochimie\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — technical/methodological paper confirming receptor functionality without deep mechanistic characterization\",\n      \"pmids\": [\"16808994\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"NPY5R PET radiotracer [18F]LuAE00654 penetrates the blood-brain barrier in baboons and shows specific in vivo binding in the striatum (highest NPY5R binding region), with up to 60% displacement by a specific NPY5R antagonist in blocking studies.\",\n      \"method\": \"PET imaging in anesthetized baboons, blocking studies with selective NPY5R antagonist, plasma metabolism analysis\",\n      \"journal\": \"ACS chemical neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo pharmacological receptor occupancy confirmed by displacement with selective antagonist\",\n      \"pmids\": [\"26886507\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NPY5R is a Gi/o-coupled GPCR that localizes to neuronal primary cilia via the BBS pathway to amplify cAMP signaling in response to NPY/PYY ligands, mediates hypothalamic control of feeding and energy homeostasis (with functional redundancy with NPY1R), drives hunger-dependent food-odour attraction through thalamic NPY release, underlies oxytocin-induced anxiolysis via PKC/eEF2-dependent de novo synthesis in the PVN, promotes cancer cell motility through RhoA activation in an autocrine NPY loop, activates hepatic ApoA1 synthesis via ERK1/2 and PKA, and stimulates granulosa cell proliferation through the MEK pathway.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NPY5R is a Gi/o-coupled receptor for neuropeptide Y (NPY) and peptide YY (PYY) that functions as a central regulator of energy homeostasis, feeding behavior, and emotional state, while also mediating peripheral proliferative and metabolic signaling. In the hypothalamus, NPY5R localizes to neuronal primary cilia via the Bardet-Biedl syndrome (BBS) trafficking pathway, and this ciliary targeting is required for normal anorexigenic responses to PYY3-36; NPY5R exhibits functional redundancy with NPY1R in central orexigenic signaling, though in the lateral hypothalamic area it becomes the dominant orexigenic receptor subtype under high-fat diet conditions [PMID:24316073, PMID:14525913, PMID:31887359]. Beyond feeding, NPY5R in the paraventricular thalamus mediates hunger-state-dependent food-odour preference, and oxytocin-driven de novo synthesis of NPY5R via PKC/eEF2 signaling in the paraventricular nucleus is required for anxiolysis [PMID:33658716, PMID:30826070]. In peripheral tissues, NPY5R couples to MAPK/ERK, PKA, and RhoA pathways to drive hepatic ApoA1 synthesis, granulosa cell proliferation, and cancer cell motility and metastasis—the latter through an autocrine NPY loop that is amplified under hypoxia via HIF-dependent transcriptional upregulation of NPY5R [PMID:35660638, PMID:31915051, PMID:40676141, PMID:35093384].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Determining whether NPY5R is individually required for NPY-driven feeding revealed functional redundancy with NPY1R, establishing that central orexigenic signaling does not depend on a single receptor subtype.\",\n      \"evidence\": \"Chronic ICV NPY infusion in Npy1r and Npy5r single-knockout mice with food intake and metabolic readouts\",\n      \"pmids\": [\"14525913\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Double Npy1r/Npy5r knockout not tested\", \"Downstream signaling pathways mediating feeding not dissected\", \"Contribution of other NPY receptor subtypes not excluded\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Pharmacological blockade of NPY5R in obese mice produced fat-selective weight loss confirmed on-target by Npy5r knockout controls, establishing NPY5R as a therapeutically relevant mediator of diet-induced obesity.\",\n      \"evidence\": \"Oral Y5 antagonist in diet-induced obese C57BL/6 vs. Npy5r−/− mice with body composition NMR and insulin tolerance tests\",\n      \"pmids\": [\"18421274\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of fat-selective weight loss not identified\", \"Long-term efficacy and compensatory receptor upregulation not assessed\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrating that NPY5R localizes to neuronal primary cilia via BBS-dependent trafficking linked ciliopathy-associated obesity to defective neuropeptide receptor signaling, showing that ciliary localization is required for PYY3-36-mediated satiety responses.\",\n      \"evidence\": \"GPCR localization screen, BBS and tubby mutant mouse models, c-fos activation, food intake, and cAMP signaling assays in ciliated vs. non-ciliated cells\",\n      \"pmids\": [\"24316073\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NPY5R signals exclusively from cilia or also from the plasma membrane not resolved\", \"Structural basis of BBS-mediated ciliary targeting of NPY5R unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Development of a brain-penetrant PET radiotracer with specific striatal binding demonstrated that NPY5R is expressed and pharmacologically accessible in vivo in primate brain, enabling future occupancy studies.\",\n      \"evidence\": \"PET imaging in baboons with [18F]LuAE00654 and displacement by selective NPY5R antagonist\",\n      \"pmids\": [\"26886507\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regional receptor density quantification not performed\", \"Translation to human imaging not yet demonstrated\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Two studies revealed region-specific NPY5R roles: in the PVN, oxytocin drives de novo NPY5R synthesis via PKC/eEF2 to mediate anxiolysis; in the LHA, NPY5R becomes the dominant orexigenic receptor under high-fat diet conditions, resolving how diet alters NPY receptor subtype dependence.\",\n      \"evidence\": \"Intra-PVN agonist/antagonist infusion with eEF2/PKC pathway dissection and anxiety tests in rats; intra-LHA NPY infusion with subtype-selective antagonists in chow vs. high-fat-fed rats\",\n      \"pmids\": [\"30826070\", \"31887359\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether eEF2-dependent NPY5R synthesis occurs in other brain regions unknown\", \"Molecular basis of diet-induced receptor subtype switching in LHA not identified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Electrophysiological dissection showed that NPY's direct inhibition of arcuate kisspeptin neurons is mediated by NPY1R, not NPY5R, delineating receptor subtype specificity in reproductive neuroendocrine circuits.\",\n      \"evidence\": \"Acute brain slice electrophysiology and calcium imaging in Kiss1-reporter mice with selective NPY1R/NPY5R antagonists and tetrodotoxin\",\n      \"pmids\": [\"32337804\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Indirect NPY5R effects via presynaptic or network mechanisms not excluded\", \"Only one hypothalamic cell type tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Circuit-level dissection established that NPY5R in the paraventricular thalamus is the specific receptor required for hunger-state-dependent switching of olfactory valence, connecting metabolic state to sensory preference.\",\n      \"evidence\": \"Npy5r knockout mice, optogenetic AGRP neuron activation, cell-specific NPY rescue, and olfactory behavioral assays\",\n      \"pmids\": [\"33658716\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream intracellular signaling in thalamic neurons not characterized\", \"Whether NPY5R modulates other sensory modalities unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Multiple studies defined peripheral NPY5R signaling: HIF-dependent transcriptional upregulation sensitizes breast cancer cells to NPY-driven MAPK/ERK signaling under hypoxia; NPY5R activates ERK1/2 and PKA to stimulate hepatic ApoA1 synthesis; and NPY5R forms a complex with NPY2R and NFATc1 in sebaceous glands linked to sebum gene regulation.\",\n      \"evidence\": \"ChIP for HIF at NPY5R locus plus MAPK assays in hypoxic breast cancer cells; hepatocyte cultures and rodent ApoA1 assays with pathway inhibitors; Co-IP/MS and ChIP-seq in sebaceous glands\",\n      \"pmids\": [\"35093384\", \"35660638\", \"37501148\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether HIF-NPY5R axis operates in non-breast cancers not tested\", \"ApoA1 regulation confirmed in cell lines and rodents but not in human hepatocytes\", \"Functional consequence of NPY2R-NPY5R-NFATc1 complex for NPY5R signaling not determined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Pharmacological NPY5R blockade under hypoxia showed enhanced anti-proliferative and anti-migratory effects in breast cancer models, and combined NPY1R/NPY5R antagonism was additive, establishing NPY5R as a hypoxia-responsive oncogenic signaling node.\",\n      \"evidence\": \"NPY1R/NPY5R antagonists in 2D/3D breast cancer models with MAPK, migration, invasion, and spheroid assays; immunofluorescence of human breast tumor tissue\",\n      \"pmids\": [\"37264315\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vivo tumor model with NPY5R antagonism\", \"Correlation of NPY5R levels with patient outcome not established causally\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"CRISPR knockout of NPY5R in Ewing sarcoma xenografts eliminated extrapulmonary metastasis and identified RhoA activation via an autocrine NPY loop as the pro-metastatic mechanism, establishing a direct requirement for NPY5R in tumor dissemination.\",\n      \"evidence\": \"Inducible CRISPR/Cas9 NPY5R KO in SK-ES-1 xenografts, in vivo metastasis assays, RhoA activation assays, motility assays\",\n      \"pmids\": [\"40676141\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RhoA activation is direct or through intermediate effectors not resolved\", \"Generalizability to other sarcoma or cancer types not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of NPY5R coupling to divergent downstream effectors (Gi/o, MAPK/ERK, PKA, RhoA) in different cell types, and whether these reflect biased agonism or cell-context-dependent signaling complexes, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No cryo-EM or crystal structure of NPY5R\", \"No systematic comparison of G-protein vs. arrestin coupling\", \"Mechanism by which ciliary vs. plasma membrane localization shapes signaling output unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1, 2, 3, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 14]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 2, 4, 5, 8, 12]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [1, 2, 6, 7]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [4, 11, 12]}\n    ],\n    \"complexes\": [\n      \"NPY2R-NPY5R-NFATc1 complex\"\n    ],\n    \"partners\": [\n      \"NPY2R\",\n      \"NFATc1\",\n      \"DYRK1A\",\n      \"RHOA\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}