{"gene":"LDLRAD3","run_date":"2026-06-13T19:06:35","timeline":{"discoveries":[],"current_model":"Parse failed"},"narrative":{"mechanistic_narrative":"No mechanistic discoveries found in literature.","teleology":[],"mechanism_profile":null},"prefetch_data":{"uniprot":{"accession":"Q86YD5","full_name":"Low-density lipoprotein receptor class A domain-containing protein 3","aliases":[],"length_aa":345,"mass_kda":37.4,"function":"May influence APP processing, resulting in a decrease in sAPP-alpha production and increased amyloidogenic P3 peptide production. May regulate ITCH and NEDD4 E3 ligase activity and degradation (PubMed:26854353) (Microbial infection) Acts as a receptor for Venezuelan equine encephalitis virus","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q86YD5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LDLRAD3","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/LDLRAD3","total_profiled":1310},"omim":[{"mim_id":"617986","title":"LOW DENSITY LIPOPROTEIN RECEPTOR CLASS A DOMAIN-CONTAINING PROTEIN 3; LDLRAD3","url":"https://www.omim.org/entry/617986"},{"mim_id":"606409","title":"ITCHY E3 UBIQUITIN PROTEIN LIGASE; ITCH","url":"https://www.omim.org/entry/606409"},{"mim_id":"602278","title":"NEURAL PRECURSOR CELL EXPRESSED, DEVELOPMENTALLY DOWNREGULATED 4; NEDD4","url":"https://www.omim.org/entry/602278"},{"mim_id":"104760","title":"AMYLOID BETA A4 PRECURSOR PROTEIN; APP","url":"https://www.omim.org/entry/104760"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cell Junctions","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":28.1}],"url":"https://www.proteinatlas.org/search/LDLRAD3"},"hgnc":{"alias_symbol":["LRAD3"],"prev_symbol":[]},"alphafold":{"accession":"Q86YD5","domains":[{"cath_id":"4.10.400.10","chopping":"28-64","consensus_level":"medium","plddt":77.3122,"start":28,"end":64},{"cath_id":"4.10.400.10","chopping":"73-106","consensus_level":"medium","plddt":78.5191,"start":73,"end":106},{"cath_id":"4.10.400.10","chopping":"107-147","consensus_level":"medium","plddt":77.0863,"start":107,"end":147},{"cath_id":"1.20.5","chopping":"169-202","consensus_level":"medium","plddt":89.0797,"start":169,"end":202}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YD5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YD5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YD5-F1-predicted_aligned_error_v6.png","plddt_mean":61.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LDLRAD3","jax_strain_url":"https://www.jax.org/strain/search?query=LDLRAD3"},"sequence":{"accession":"Q86YD5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86YD5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86YD5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YD5"}},"corpus_meta":[{"pmid":"29307994","id":"PMC_29307994","title":"Circular RNA circ-LDLRAD3 as a biomarker in diagnosis of pancreatic cancer.","date":"2017","source":"World journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/29307994","citation_count":160,"is_preprint":false},{"pmid":"33208938","id":"PMC_33208938","title":"LDLRAD3 is a receptor for Venezuelan equine encephalitis virus.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/33208938","citation_count":137,"is_preprint":false},{"pmid":"31521692","id":"PMC_31521692","title":"Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.","date":"2019","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31521692","citation_count":61,"is_preprint":false},{"pmid":"34646021","id":"PMC_34646021","title":"Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34646021","citation_count":52,"is_preprint":false},{"pmid":"34646020","id":"PMC_34646020","title":"Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34646020","citation_count":48,"is_preprint":false},{"pmid":"21795536","id":"PMC_21795536","title":"LRAD3, a novel low-density lipoprotein receptor family member that modulates amyloid precursor protein trafficking.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21795536","citation_count":41,"is_preprint":false},{"pmid":"32658600","id":"PMC_32658600","title":"Circular RNA circ-LDLRAD3 serves as an oncogene to promote non-small cell lung cancer progression by upregulating SLC1A5 through sponging miR-137.","date":"2020","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/32658600","citation_count":37,"is_preprint":false},{"pmid":"26854353","id":"PMC_26854353","title":"Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by LRAD3.","date":"2016","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26854353","citation_count":21,"is_preprint":false},{"pmid":"35975639","id":"PMC_35975639","title":"circ-LDLRAD3 Knockdown Reduces Cisplatin Chemoresistance and Inhibits the Development of Gastric Cancer with Cisplatin Resistance through miR-588 Enrichment-Mediated SOX5 Inhibition.","date":"2022","source":"Gut and liver","url":"https://pubmed.ncbi.nlm.nih.gov/35975639","citation_count":21,"is_preprint":false},{"pmid":"33389349","id":"PMC_33389349","title":"Circ-LDLRAD3 Enhances Cell Growth, Migration, and Invasion and Inhibits Apoptosis by Regulating MiR-224-5p/NRP2 Axis in Gastric Cancer.","date":"2021","source":"Digestive diseases and sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33389349","citation_count":15,"is_preprint":false},{"pmid":"37556325","id":"PMC_37556325","title":"Entry receptor LDLRAD3 is required for Venezuelan equine encephalitis virus peripheral infection and neurotropism leading to pathogenesis in mice.","date":"2023","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/37556325","citation_count":13,"is_preprint":false},{"pmid":"37587156","id":"PMC_37587156","title":"Expression status of circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 in patients with colorectal cancer.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37587156","citation_count":10,"is_preprint":false},{"pmid":"35035814","id":"PMC_35035814","title":"circRNA LDLRAD3 Enhances the Malignant Behaviors of NSCLC Cells via the miR-20a-5p-SLC7A5 Axis Activating the mTORC1 Signaling Pathway.","date":"2022","source":"Journal of healthcare engineering","url":"https://pubmed.ncbi.nlm.nih.gov/35035814","citation_count":3,"is_preprint":false},{"pmid":"39161132","id":"PMC_39161132","title":"Circular RNA LDLRAD3 promotes gastric cancer progression by upregulating COL4A5 through sponging miR-h37.","date":"2024","source":"Journal of the Chinese Medical Association : JCMA","url":"https://pubmed.ncbi.nlm.nih.gov/39161132","citation_count":1,"is_preprint":false},{"pmid":"38430029","id":"PMC_38430029","title":"Circ-LDLRAD3/miR-655-3p/MAPK1 axis enhances cell migration and invasion in papillary thyroid carcinoma.","date":"2024","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/38430029","citation_count":0,"is_preprint":false},{"pmid":"41344818","id":"PMC_41344818","title":"Transcriptomic and experimental validation identifies SOX6 and LDLRAD3 as key factors in vascular dementia.","date":"2026","source":"The journals of gerontology. Series A, Biological sciences and medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41344818","citation_count":0,"is_preprint":false},{"pmid":"40583129","id":"PMC_40583129","title":"Chemically Synthesized LRAD3-D1 Interacts with N-Terminal Domain of SARS-CoV-2 Spike Protein.","date":"2025","source":"Chembiochem : a European journal of chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/40583129","citation_count":0,"is_preprint":false},{"pmid":"37886338","id":"PMC_37886338","title":"Retracted: circRNA LDLRAD3 Enhances the Malignant Behaviors of NSCLC Cells via the miR-20a-5p-SLC7A5 Axis Activating the mTORC1 Signaling Pathway.","date":"2023","source":"Journal of healthcare engineering","url":"https://pubmed.ncbi.nlm.nih.gov/37886338","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10946,"output_tokens":623,"usd":0.021091,"stage1_stop_reason":"refusal"},"stage2":{"model":"","input_tokens":0,"output_tokens":0,"usd":0.0},"total_usd":0.021091,"stage1_batch_id":"msgbatch_0147LFpL5iCPFZF66xp23BqC","stage2_batch_id":"msgbatch_01Crtwc6eCsZh1CrnfJhY7J7","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"LDLRAD3 (LRAD3) is a type I transmembrane receptor expressed in neurons that physically interacts with amyloid precursor protein (APP), specifically with the C99 β-secretase product (but not sAPPα), and promotes the amyloidogenic processing of APP, resulting in decreased sAPPα production, increased Aβ peptide production, and reduced cellular half-life of mature APP.\",\n      \"method\": \"Coimmunoprecipitation, solid-phase binding assay, pulse-chase experiments, cell-based overexpression in HT22 neuronal cells\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and multiple orthogonal assays (solid-phase binding, pulse-chase) in a single lab\",\n      \"pmids\": [\"21795536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"LDLRAD3 (LRAD3) activates the E3 ubiquitin ligases Itch and Nedd4 via its intracellular PPxY motifs binding to their WW domains, promoting auto-ubiquitination and subsequent proteasomal degradation of these ligases; the terminal PPxY motif of LRAD3 is specifically required for Itch auto-ubiquitination.\",\n      \"method\": \"Mutational analysis of PPxY motifs, ubiquitination assays, proteasome inhibitor experiments, binding affinity assays\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis combined with functional ubiquitination assays and degradation assays in a single lab\",\n      \"pmids\": [\"26854353\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"LDLRAD3 is an entry receptor for Venezuelan equine encephalitis virus (VEEV); it binds directly to VEEV particles and enhances virus attachment and internalization into host cells. Domain 1 (D1) of LDLRAD3 is necessary and sufficient to support VEEV infection. Gene","stage2_raw":"","audit_flag":{"gene":"LDLRAD3","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"recall_miss","uniprot_band":"medium","rules_fired":"R5","issue":"R5: no narrative despite experimental UniProt FUNCTION (292 chars) and on-target evidence in corpus (18 on-target corpus titles)"},"evaluation":null}