{"gene":"NID2","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2016,"finding":"NID2 re-expression in nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC) cells suppresses clonogenic survival, migration, and liver metastasis, and mechanistically inhibits the EGFR/Akt and integrin/FAK/PLCγ signaling pathways.","method":"Stable re-expression (transduction) of NID2 in NPC/ESCC cell lines with clonogenic survival assays, migration assays, in vivo metastasis models, and Western blot analysis of signaling pathway components","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 — KO/OE with defined cellular phenotype and pathway placement in two cancer models; single lab, multiple orthogonal methods","pmids":["27793011"],"is_preprint":false},{"year":2019,"finding":"NID2 overexpression or demethylation in lung cancer cells reduces cell viability, proliferation, migration, and invasion while increasing apoptosis; NID2 overexpression inhibits tumor growth in nude mouse xenograft models, establishing NID2 as a tumor suppressor whose silencing by DNA hypermethylation promotes lung cancer.","method":"NID2 overexpression and demethylation in lung cancer cell lines; CCK-8 assay, colony formation, transwell, wound healing, flow cytometry for apoptosis, and nude mouse xenograft models; Western blot and RT-PCR for protein/mRNA validation","journal":"Pathology oncology research : POR","confidence":"Medium","confidence_rationale":"Tier 2 — multiple functional assays with in vivo validation; single lab","pmids":["30826972"],"is_preprint":false},{"year":2025,"finding":"NID2 mediates diabetic vascular calcification by activating the downstream IGF2-ERK1/2 signaling pathway; EETs (particularly 11,12-EET and 14,15-EET) prevent osteogenic transdifferentiation of vascular smooth muscle cells by decreasing NID2 expression, and NID2 overexpression abolished the inhibitory effect of sEH gene deletion on vascular calcification.","method":"sEH gene knockout mice (Ephx2-/-), NID2 overexpression via AAV9 vectors in vivo, siRNA knockdown and pharmacological sEH inhibitors in MOVAS cells, Western blot for IGF2 and phospho-ERK1/2, alizarin red and Von Kossa staining for calcification","journal":"Chinese medical journal","confidence":"Medium","confidence_rationale":"Tier 2 — genetic rescue and epistasis in vivo plus in vitro mechanistic follow-up; single lab, multiple orthogonal methods","pmids":["40937642"],"is_preprint":false},{"year":2025,"finding":"Extracellular vesicles (EVs) from ciliated fibroblasts modestly enhance early ECM remodeling in recipient cells via induction of Nid2 expression, suggesting NID2 participates in paracrine ECM-remodeling signaling downstream of primary cilium activity.","method":"Conditioned medium fractionation, transcriptomic profiling of target cells after EV treatment, wound healing assay in primary cilium-deficient fibroblasts","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 — single preprint, indirect induction of Nid2 expression; no direct NID2 functional manipulation","pmids":["bio_10.1101_2025.08.20.671189"],"is_preprint":true}],"current_model":"NID2 is a basement membrane component that functions as a tumor/metastasis suppressor by inhibiting EGFR/Akt and integrin/FAK/PLCγ signaling pathways; its promoter is frequently silenced by DNA hypermethylation in multiple cancers, and in vascular smooth muscle cells NID2 promotes osteogenic transdifferentiation by activating an IGF2-ERK1/2 signaling axis downstream of EET levels regulated by soluble epoxide hydrolase."},"narrative":{"teleology":[{"year":2016,"claim":"Establishing NID2 as a functional tumor/metastasis suppressor resolved the question of whether its epigenetic silencing in carcinomas was causally linked to malignant phenotypes, revealing that NID2 re-expression inhibits EGFR/Akt and integrin/FAK/PLCγ signaling to suppress clonogenicity, migration, and liver metastasis.","evidence":"Stable NID2 re-expression in NPC and ESCC cell lines with clonogenic, migration, in vivo metastasis assays, and Western blot of pathway components","pmids":["27793011"],"confidence":"Medium","gaps":["Direct physical interaction between NID2 and EGFR or integrins has not been demonstrated","Whether NID2 suppressor function is universal across cancer types or tissue-specific is unclear","No structural or biochemical basis for how extracellular NID2 modulates intracellular EGFR/Akt signaling"]},{"year":2019,"claim":"Extending the tumor-suppressive role to lung cancer and demonstrating that NID2 overexpression induces apoptosis and inhibits xenograft growth reinforced NID2 as a broadly acting epithelial tumor suppressor silenced by DNA methylation.","evidence":"NID2 overexpression and demethylation in lung cancer cell lines with CCK-8, colony formation, transwell, apoptosis assays, and nude mouse xenograft models","pmids":["30826972"],"confidence":"Medium","gaps":["Downstream signaling pathway specifics in lung cancer were not mapped as thoroughly as in NPC/ESCC","No loss-of-function genetics in normal tissue to establish physiological requirement","Apoptotic mechanism (intrinsic vs. extrinsic) induced by NID2 remains undefined"]},{"year":2025,"claim":"Demonstrating that NID2 promotes vascular calcification via IGF2-ERK1/2 activation revealed a non-oncological, tissue-specific function in osteogenic transdifferentiation of smooth muscle cells, regulated upstream by EET-dependent suppression of NID2 expression.","evidence":"Ephx2-/- mice, AAV9-mediated NID2 overexpression in vivo, siRNA knockdown and sEH inhibitors in MOVAS cells, Western blot for IGF2/p-ERK1/2, calcification staining","pmids":["40937642"],"confidence":"Medium","gaps":["How NID2, an extracellular matrix protein, activates intracellular IGF2-ERK1/2 signaling is mechanistically unresolved","Whether NID2-driven calcification involves the same integrin/EGFR pathways implicated in cancer is unknown","Single lab; independent replication pending"]},{"year":null,"claim":"The receptor(s) and direct molecular partners through which extracellular NID2 transduces signals into intracellular EGFR/Akt, integrin/FAK, and IGF2-ERK1/2 pathways remain unidentified, and no loss-of-function genetic model in normal epithelial tissue has established its physiological basement membrane role.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct NID2-receptor binding partner has been biochemically identified","No Nid2 knockout mouse phenotype characterization in the literature captured here","Structural basis for NID2 integration into basement membrane and signaling is lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0,1,2]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-1474244","term_label":"Extracellular matrix organization","supporting_discovery_ids":[0,2]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"NID2 is a basement membrane glycoprotein that functions as a tumor suppressor silenced by promoter DNA hypermethylation in multiple epithelial cancers; re-expression in nasopharyngeal, esophageal, and lung cancer cells suppresses clonogenic survival, migration, invasion, and in vivo tumor growth and metastasis by inhibiting EGFR/Akt and integrin/FAK/PLCγ signaling pathways [PMID:27793011, PMID:30826972]. In vascular smooth muscle cells, NID2 promotes osteogenic transdifferentiation and diabetic vascular calcification by activating an IGF2-ERK1/2 signaling axis, a process normally restrained by epoxyeicosatrienoic acids (EETs) that suppress NID2 expression [PMID:40937642]."},"prefetch_data":{"uniprot":{"accession":"Q14112","full_name":"Nidogen-2","aliases":["Osteonidogen"],"length_aa":1375,"mass_kda":151.3,"function":"Cell adhesion glycoprotein which is widely distributed in basement membranes. Binds to collagens I and IV, to perlecan and to laminin 1. Does not bind fibulins. It probably has a role in cell-extracellular matrix interactions","subcellular_location":"Secreted, extracellular space, extracellular matrix, basement membrane","url":"https://www.uniprot.org/uniprotkb/Q14112/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NID2","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/NID2","total_profiled":1310},"omim":[{"mim_id":"605399","title":"NIDOGEN 2; NID2","url":"https://www.omim.org/entry/605399"},{"mim_id":"604633","title":"EGF-CONTAINING FIBULIN-LIKE EXTRACELLULAR MATRIX PROTEIN 2; EFEMP2","url":"https://www.omim.org/entry/604633"},{"mim_id":"131390","title":"NIDOGEN 1; NID1","url":"https://www.omim.org/entry/131390"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"ovary","ntpm":57.9},{"tissue":"placenta","ntpm":57.1}],"url":"https://www.proteinatlas.org/search/NID2"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q14112","domains":[{"cath_id":"-","chopping":"34-169_177-282","consensus_level":"high","plddt":84.9721,"start":34,"end":282},{"cath_id":"2.40.155.10","chopping":"516-751","consensus_level":"high","plddt":88.7235,"start":516,"end":751},{"cath_id":"2.10.25.10","chopping":"762-803","consensus_level":"medium","plddt":80.7067,"start":762,"end":803},{"cath_id":"2.10.25,2.10.25","chopping":"809-845","consensus_level":"high","plddt":78.1911,"start":809,"end":845},{"cath_id":"-","chopping":"968-1004","consensus_level":"medium","plddt":82.157,"start":968,"end":1004},{"cath_id":"4.10.800.10","chopping":"1018-1087","consensus_level":"medium","plddt":78.8389,"start":1018,"end":1087},{"cath_id":"2.120.10.30","chopping":"1110-1367","consensus_level":"medium","plddt":91.2048,"start":1110,"end":1367}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14112","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14112-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14112-F1-predicted_aligned_error_v6.png","plddt_mean":73.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NID2","jax_strain_url":"https://www.jax.org/strain/search?query=NID2"},"sequence":{"accession":"Q14112","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14112.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14112/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14112"}},"corpus_meta":[{"pmid":"19674832","id":"PMC_19674832","title":"Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples.","date":"2009","source":"European urology","url":"https://pubmed.ncbi.nlm.nih.gov/19674832","citation_count":124,"is_preprint":false},{"pmid":"21558411","id":"PMC_21558411","title":"NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva.","date":"2011","source":"Cancer prevention research (Philadelphia, Pa.)","url":"https://pubmed.ncbi.nlm.nih.gov/21558411","citation_count":110,"is_preprint":false},{"pmid":"23682613","id":"PMC_23682613","title":"Hypermethylation of TWIST1 and NID2 in tumor tissues and voided urine in urinary bladder cancer patients.","date":"2013","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/23682613","citation_count":37,"is_preprint":false},{"pmid":"27793011","id":"PMC_27793011","title":"Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27793011","citation_count":30,"is_preprint":false},{"pmid":"23083854","id":"PMC_23083854","title":"Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer.","date":"2012","source":"The Journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/23083854","citation_count":29,"is_preprint":false},{"pmid":"26027762","id":"PMC_26027762","title":"Multi-institutional external validation of urinary TWIST1 and NID2 methylation as a diagnostic test for bladder cancer.","date":"2015","source":"Urologic oncology","url":"https://pubmed.ncbi.nlm.nih.gov/26027762","citation_count":28,"is_preprint":false},{"pmid":"28106542","id":"PMC_28106542","title":"Urinary NID2 and TWIST1 methylation to augment conventional urine cytology for the detection of bladder cancer.","date":"2017","source":"Cancer biomarkers : section A of Disease markers","url":"https://pubmed.ncbi.nlm.nih.gov/28106542","citation_count":23,"is_preprint":false},{"pmid":"22741015","id":"PMC_22741015","title":"Methylation status of NEUROG2 and NID2 improves the diagnosis of stage I NSCLC.","date":"2012","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/22741015","citation_count":21,"is_preprint":false},{"pmid":"32171289","id":"PMC_32171289","title":"Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma.","date":"2020","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/32171289","citation_count":18,"is_preprint":false},{"pmid":"30826972","id":"PMC_30826972","title":"Silencing NID2 by DNA Hypermethylation Promotes Lung Cancer.","date":"2019","source":"Pathology oncology research : POR","url":"https://pubmed.ncbi.nlm.nih.gov/30826972","citation_count":15,"is_preprint":false},{"pmid":"34922269","id":"PMC_34922269","title":"Evaluation of DNA methylation in promoter regions of hTERT, TWIST1, VIM and NID2 genes in Moroccan bladder cancer patients.","date":"2021","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34922269","citation_count":13,"is_preprint":false},{"pmid":"36908806","id":"PMC_36908806","title":"Nidogen-2 (NID2) is a Key Factor in Collagen Causing Poor Response to Immunotherapy in Melanoma.","date":"2023","source":"Pharmacogenomics and personalized medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36908806","citation_count":2,"is_preprint":false},{"pmid":"40937642","id":"PMC_40937642","title":"Diabetic vascular calcification inhibited by soluble epoxide hydrolase gene deletion via regressing NID2-mediated IGF2-ERK1/2 signaling pathway.","date":"2025","source":"Chinese medical journal","url":"https://pubmed.ncbi.nlm.nih.gov/40937642","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.20.671189","title":"Primary Cilium-dependent Humoral Bioactive Factors Acts in a Paracrine Manner to Control Fibroblast Cell Migration","date":"2025-08-20","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.20.671189","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9148,"output_tokens":1147,"usd":0.022325},"stage2":{"model":"claude-opus-4-6","input_tokens":4353,"output_tokens":1405,"usd":0.085335},"total_usd":0.10766,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"NID2 re-expression in nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC) cells suppresses clonogenic survival, migration, and liver metastasis, and mechanistically inhibits the EGFR/Akt and integrin/FAK/PLCγ signaling pathways.\",\n      \"method\": \"Stable re-expression (transduction) of NID2 in NPC/ESCC cell lines with clonogenic survival assays, migration assays, in vivo metastasis models, and Western blot analysis of signaling pathway components\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KO/OE with defined cellular phenotype and pathway placement in two cancer models; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"27793011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"NID2 overexpression or demethylation in lung cancer cells reduces cell viability, proliferation, migration, and invasion while increasing apoptosis; NID2 overexpression inhibits tumor growth in nude mouse xenograft models, establishing NID2 as a tumor suppressor whose silencing by DNA hypermethylation promotes lung cancer.\",\n      \"method\": \"NID2 overexpression and demethylation in lung cancer cell lines; CCK-8 assay, colony formation, transwell, wound healing, flow cytometry for apoptosis, and nude mouse xenograft models; Western blot and RT-PCR for protein/mRNA validation\",\n      \"journal\": \"Pathology oncology research : POR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple functional assays with in vivo validation; single lab\",\n      \"pmids\": [\"30826972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NID2 mediates diabetic vascular calcification by activating the downstream IGF2-ERK1/2 signaling pathway; EETs (particularly 11,12-EET and 14,15-EET) prevent osteogenic transdifferentiation of vascular smooth muscle cells by decreasing NID2 expression, and NID2 overexpression abolished the inhibitory effect of sEH gene deletion on vascular calcification.\",\n      \"method\": \"sEH gene knockout mice (Ephx2-/-), NID2 overexpression via AAV9 vectors in vivo, siRNA knockdown and pharmacological sEH inhibitors in MOVAS cells, Western blot for IGF2 and phospho-ERK1/2, alizarin red and Von Kossa staining for calcification\",\n      \"journal\": \"Chinese medical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic rescue and epistasis in vivo plus in vitro mechanistic follow-up; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40937642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Extracellular vesicles (EVs) from ciliated fibroblasts modestly enhance early ECM remodeling in recipient cells via induction of Nid2 expression, suggesting NID2 participates in paracrine ECM-remodeling signaling downstream of primary cilium activity.\",\n      \"method\": \"Conditioned medium fractionation, transcriptomic profiling of target cells after EV treatment, wound healing assay in primary cilium-deficient fibroblasts\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single preprint, indirect induction of Nid2 expression; no direct NID2 functional manipulation\",\n      \"pmids\": [\"bio_10.1101_2025.08.20.671189\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NID2 is a basement membrane component that functions as a tumor/metastasis suppressor by inhibiting EGFR/Akt and integrin/FAK/PLCγ signaling pathways; its promoter is frequently silenced by DNA hypermethylation in multiple cancers, and in vascular smooth muscle cells NID2 promotes osteogenic transdifferentiation by activating an IGF2-ERK1/2 signaling axis downstream of EET levels regulated by soluble epoxide hydrolase.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NID2 is a basement membrane glycoprotein that functions as a tumor suppressor silenced by promoter DNA hypermethylation in multiple epithelial cancers; re-expression in nasopharyngeal, esophageal, and lung cancer cells suppresses clonogenic survival, migration, invasion, and in vivo tumor growth and metastasis by inhibiting EGFR/Akt and integrin/FAK/PLCγ signaling pathways [PMID:27793011, PMID:30826972]. In vascular smooth muscle cells, NID2 promotes osteogenic transdifferentiation and diabetic vascular calcification by activating an IGF2-ERK1/2 signaling axis, a process normally restrained by epoxyeicosatrienoic acids (EETs) that suppress NID2 expression [PMID:40937642].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing NID2 as a functional tumor/metastasis suppressor resolved the question of whether its epigenetic silencing in carcinomas was causally linked to malignant phenotypes, revealing that NID2 re-expression inhibits EGFR/Akt and integrin/FAK/PLCγ signaling to suppress clonogenicity, migration, and liver metastasis.\",\n      \"evidence\": \"Stable NID2 re-expression in NPC and ESCC cell lines with clonogenic, migration, in vivo metastasis assays, and Western blot of pathway components\",\n      \"pmids\": [\"27793011\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct physical interaction between NID2 and EGFR or integrins has not been demonstrated\",\n        \"Whether NID2 suppressor function is universal across cancer types or tissue-specific is unclear\",\n        \"No structural or biochemical basis for how extracellular NID2 modulates intracellular EGFR/Akt signaling\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extending the tumor-suppressive role to lung cancer and demonstrating that NID2 overexpression induces apoptosis and inhibits xenograft growth reinforced NID2 as a broadly acting epithelial tumor suppressor silenced by DNA methylation.\",\n      \"evidence\": \"NID2 overexpression and demethylation in lung cancer cell lines with CCK-8, colony formation, transwell, apoptosis assays, and nude mouse xenograft models\",\n      \"pmids\": [\"30826972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Downstream signaling pathway specifics in lung cancer were not mapped as thoroughly as in NPC/ESCC\",\n        \"No loss-of-function genetics in normal tissue to establish physiological requirement\",\n        \"Apoptotic mechanism (intrinsic vs. extrinsic) induced by NID2 remains undefined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrating that NID2 promotes vascular calcification via IGF2-ERK1/2 activation revealed a non-oncological, tissue-specific function in osteogenic transdifferentiation of smooth muscle cells, regulated upstream by EET-dependent suppression of NID2 expression.\",\n      \"evidence\": \"Ephx2-/- mice, AAV9-mediated NID2 overexpression in vivo, siRNA knockdown and sEH inhibitors in MOVAS cells, Western blot for IGF2/p-ERK1/2, calcification staining\",\n      \"pmids\": [\"40937642\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"How NID2, an extracellular matrix protein, activates intracellular IGF2-ERK1/2 signaling is mechanistically unresolved\",\n        \"Whether NID2-driven calcification involves the same integrin/EGFR pathways implicated in cancer is unknown\",\n        \"Single lab; independent replication pending\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The receptor(s) and direct molecular partners through which extracellular NID2 transduces signals into intracellular EGFR/Akt, integrin/FAK, and IGF2-ERK1/2 pathways remain unidentified, and no loss-of-function genetic model in normal epithelial tissue has established its physiological basement membrane role.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct NID2-receptor binding partner has been biochemically identified\",\n        \"No Nid2 knockout mouse phenotype characterization in the literature captured here\",\n        \"Structural basis for NID2 integration into basement membrane and signaling is lacking\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-1474244\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}