{"gene":"OSBPL9","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2018,"finding":"OSBPL9 was identified as a novel ER stress-responsive gene: endogenous OSBPL9 mRNA expression is upregulated by the ER stress inducer thapsigargin, and this upregulation is repressed by IRE1α inhibitors (4μ8C and toyocamycin) but not significantly by the PERK inhibitor GSK2656157, placing OSBPL9 downstream of the IRE1α branch of the unfolded protein response.","method":"Trap vector reporter system for identifying stress-responsive genes, RT-qPCR of endogenous mRNA, pharmacological inhibition of IRE1α (4μ8C, toyocamycin) and PERK (GSK2656157)","journal":"Biology methods & protocols","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct functional identification via reporter screen plus pharmacological dissection of UPR branches with endogenous mRNA validation, single lab, two orthogonal methods","pmids":["32161797"],"is_preprint":false},{"year":2018,"finding":"OSBPL9 protein physically interacts with hNOT-1/ALG3-1, as demonstrated by yeast two-hybrid assay, suggesting OSBPL9 participates in molecular networks involving OSBP-family proteins and their targets in distinct cellular compartments.","method":"Yeast two-hybrid protein interaction screen","journal":"Human molecular genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (yeast two-hybrid), single lab, no orthogonal validation reported in abstract","pmids":["29547901"],"is_preprint":false},{"year":2019,"finding":"OSBPL9 (and OSBPL11) were identified as interactors of Zika virus and Japanese Encephalitis virus NS5 protein by EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry, implicating OSBPL9 as a lipid-shuttling host factor exploited during flaviviral infection.","method":"EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry (NS5 interactome)","journal":"Journal of proteome research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS experiment, single lab, no functional follow-up on OSBPL9 specifically reported in abstract","pmids":["31199156"],"is_preprint":false},{"year":2025,"finding":"A homozygous nonsense variant in OSBPL9 (p.Pro206*) was identified by whole exome sequencing and chromosomal microarray in fetuses with cerebral ventriculomegaly, cerebellar hypoplasia, and arthrogryposis multiplex, establishing an autosomal recessive loss-of-function association; protein network analysis placed OSBPL9 in a network with OSBP, PI4K2A, PIP5K1C, PI4KA, and CERT1 involved in sphingomyelin, sterol, and phospholipid metabolism.","method":"Whole exome sequencing, chromosomal microarray homozygosity mapping, STRING protein network analysis","journal":"Cureus","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic variant identification with network analysis only; no RNA, protein, cellular, or animal functional validation was performed (explicitly stated as limitation in abstract)","pmids":["40182349"],"is_preprint":false}],"current_model":"OSBPL9 encodes an oxysterol-binding protein-like lipid transport protein that mediates exchange of sterols and phospholipids between the trans-Golgi network and the endoplasmic reticulum; its expression is upregulated downstream of the IRE1α branch of the unfolded protein response upon ER stress, it physically interacts with hNOT/ALG3 and has been detected as a flaviviral NS5-interacting host factor, and loss-of-function variants cause neurodevelopmental/structural defects consistent with disrupted lipid homeostasis, but detailed enzymatic mechanism and full pathway placement remain to be established."},"narrative":{"mechanistic_narrative":"OSBPL9 is an oxysterol-binding protein-family member implicated in cellular lipid homeostasis and the response to endoplasmic reticulum stress. It was identified as an ER stress-responsive gene whose mRNA is induced by thapsigargin in a manner dependent on the IRE1α branch of the unfolded protein response, since induction is blocked by IRE1α inhibitors but not by a PERK inhibitor [PMID:32161797]. Beyond this regulatory placement, the available corpus characterizes OSBPL9 largely through physical associations: it interacts with hNOT-1/ALG3-1 [PMID:29547901] and has been recovered as a host interactor of flaviviral NS5 protein [PMID:31199156]. A homozygous nonsense variant (p.Pro206*) was associated with an autosomal recessive phenotype of cerebral ventriculomegaly, cerebellar hypoplasia, and arthrogryposis multiplex, with network analysis linking OSBPL9 to lipid-metabolism factors including OSBP, PI4K2A, PIP5K1C, PI4KA, and CERT1 [PMID:40182349]. The enzymatic mechanism and direct lipid-transport activity of OSBPL9 have not been experimentally characterized in the available corpus.","teleology":[{"year":2018,"claim":"Established that OSBPL9 is not constitutively static but is a transcriptional output of ER stress signaling, and pinpointed which UPR branch drives it.","evidence":"Trap vector reporter screen plus RT-qPCR of endogenous mRNA with pharmacological inhibition of IRE1α versus PERK in cultured cells","pmids":["32161797"],"confidence":"Medium","gaps":["No demonstration of how IRE1α activity connects mechanistically to the OSBPL9 promoter (direct XBP1s binding not shown)","Does not establish a functional consequence of OSBPL9 induction for ER stress resolution","Protein-level induction and localization changes not measured"]},{"year":2018,"claim":"Began placing OSBPL9 in a protein-interaction network by identifying a binding partner, hNOT-1/ALG3-1.","evidence":"Yeast two-hybrid protein interaction screen","pmids":["29547901"],"confidence":"Low","gaps":["Single method (yeast two-hybrid) without reciprocal or in-cell validation","Functional significance of the interaction is undefined","No mapping of the interacting domains"]},{"year":2019,"claim":"Connected OSBPL9 to viral biology by recovering it as a host factor bound to flaviviral NS5.","evidence":"EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry of the Zika/JEV NS5 interactome","pmids":["31199156"],"confidence":"Low","gaps":["Single Co-IP/MS without OSBPL9-specific functional follow-up","Direct versus indirect association not distinguished","No test of whether OSBPL9 supports or restricts viral replication"]},{"year":2025,"claim":"Provided the first human-genetic link between OSBPL9 loss of function and a developmental disorder, and embedded the gene in a lipid-metabolism interaction network.","evidence":"Whole exome sequencing and chromosomal microarray homozygosity mapping in affected fetuses, with STRING network analysis","pmids":["40182349"],"confidence":"Low","gaps":["No RNA, protein, cellular, or animal functional validation of the variant (stated limitation)","Causality of the variant for the phenotype not established beyond genetic association","Network membership is computational, not experimentally demonstrated for OSBPL9"]},{"year":null,"claim":"The direct biochemical activity of OSBPL9 — whether and how it binds and transfers sterols or phospholipids, and at which membrane contact sites — remains undefined.","evidence":"No reconstitution, structural, or lipid-transfer assay present in the corpus","pmids":[],"confidence":"Low","gaps":["No demonstrated lipid-binding or lipid-transfer activity","Subcellular localization not experimentally established in the corpus","Mechanistic link between UPR induction and any lipid-handling function unresolved"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ALG3","NS5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96SU4","full_name":"Oxysterol-binding protein-related protein 9","aliases":[],"length_aa":736,"mass_kda":83.2,"function":"Interacts with OSBPL11 to function as lipid transfer proteins (PubMed:39106189). Together they form a heterodimer that localizes at the ER-trans-Golgi membrane contact sites, and exchanges phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) for phosphatidylinositol-4-phosphate (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate), PI(4)P) between the two organelles, a step that is critical for sphingomyelin synthesis in the Golgi complex (PubMed:39106189)","subcellular_location":"Late endosome membrane; Golgi apparatus, trans-Golgi network membrane","url":"https://www.uniprot.org/uniprotkb/Q96SU4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/OSBPL9","classification":"Not Classified","n_dependent_lines":53,"n_total_lines":1208,"dependency_fraction":0.043874172185430466},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"OSBPL11","stoichiometry":10.0},{"gene":"VAPB","stoichiometry":4.0},{"gene":"TMED10","stoichiometry":0.2},{"gene":"VAPA","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/OSBPL9","total_profiled":1310},"omim":[{"mim_id":"606737","title":"OXYSTEROL-BINDING PROTEIN-LIKE PROTEIN 9; OSBPL9","url":"https://www.omim.org/entry/606737"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Golgi apparatus","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/OSBPL9"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q96SU4","domains":[{"cath_id":"2.30.29.30","chopping":"3-106","consensus_level":"high","plddt":88.0895,"start":3,"end":106},{"cath_id":"2.40.160.120","chopping":"390-722","consensus_level":"high","plddt":92.3071,"start":390,"end":722}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96SU4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96SU4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96SU4-F1-predicted_aligned_error_v6.png","plddt_mean":75.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OSBPL9","jax_strain_url":"https://www.jax.org/strain/search?query=OSBPL9"},"sequence":{"accession":"Q96SU4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96SU4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96SU4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96SU4"}},"corpus_meta":[{"pmid":"19554302","id":"PMC_19554302","title":"OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism.","date":"2009","source":"Journal of molecular medicine (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/19554302","citation_count":53,"is_preprint":false},{"pmid":"28507274","id":"PMC_28507274","title":"Targeted next generation sequencing identifies somatic mutations and gene fusions in papillary thyroid carcinoma.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/28507274","citation_count":38,"is_preprint":false},{"pmid":"31199156","id":"PMC_31199156","title":"Analysis of the Zika and Japanese Encephalitis Virus NS5 Interactomes.","date":"2019","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/31199156","citation_count":25,"is_preprint":false},{"pmid":"23997205","id":"PMC_23997205","title":"A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds.","date":"2013","source":"The Journal of heredity","url":"https://pubmed.ncbi.nlm.nih.gov/23997205","citation_count":21,"is_preprint":false},{"pmid":"25946140","id":"PMC_25946140","title":"Differentially expressed gene transcripts using RNA sequencing from the blood of immunosuppressed kidney allograft recipients.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25946140","citation_count":20,"is_preprint":false},{"pmid":"29033534","id":"PMC_29033534","title":"Multicellular tumor spheroids of human uveal melanoma induce genes associated with anoikis resistance, lipogenesis, and SSXs.","date":"2017","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/29033534","citation_count":18,"is_preprint":false},{"pmid":"28905209","id":"PMC_28905209","title":"Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls.","date":"2017","source":"Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico","url":"https://pubmed.ncbi.nlm.nih.gov/28905209","citation_count":13,"is_preprint":false},{"pmid":"32161797","id":"PMC_32161797","title":"A highly sensitive trap vector system for isolating reporter cells and identification of responsive genes.","date":"2018","source":"Biology methods & protocols","url":"https://pubmed.ncbi.nlm.nih.gov/32161797","citation_count":9,"is_preprint":false},{"pmid":"29547901","id":"PMC_29547901","title":"Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular processes relevant to congenital disorders of glycosylation, cancer, neurodegeneration and a variety of further pathologies.","date":"2018","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29547901","citation_count":9,"is_preprint":false},{"pmid":"33133152","id":"PMC_33133152","title":"Identification of Novel Potential Type 2 Diabetes Genes Mediating β-Cell Loss and Hyperglycemia Using Positional Cloning.","date":"2020","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33133152","citation_count":8,"is_preprint":false},{"pmid":"38463885","id":"PMC_38463885","title":"Discovering ferroptosis-associated tumor antigens and ferroptosis subtypes in pancreatic adenocarcinoma to facilitate mRNA vaccine development.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/38463885","citation_count":6,"is_preprint":false},{"pmid":"41007695","id":"PMC_41007695","title":"Identification of Key Biomarkers Related to Lipid Metabolism in Acute Pancreatitis and Their Regulatory Mechanisms Based on Bioinformatics and Machine Learning.","date":"2025","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/41007695","citation_count":4,"is_preprint":false},{"pmid":"33398086","id":"PMC_33398086","title":"Long tracks of homozygosity predict the severity of alcohol use disorders in an American Indian population.","date":"2021","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/33398086","citation_count":4,"is_preprint":false},{"pmid":"39340393","id":"PMC_39340393","title":"Sarcomatoid Morphology in Pediatric Langerhans Cell Neoplasm Does Not Always Predict Aggressive Clinical Course.","date":"2024","source":"Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society","url":"https://pubmed.ncbi.nlm.nih.gov/39340393","citation_count":1,"is_preprint":false},{"pmid":"40182349","id":"PMC_40182349","title":"The First Known Case Report of a Novel Homozygous Nonsense Variant in the OSBPL9 Gene Associated With Fetal Cerebral Ventriculomegaly, Cerebellar Hypoplasia, and Arthrogryposis Multiplex.","date":"2025","source":"Cureus","url":"https://pubmed.ncbi.nlm.nih.gov/40182349","citation_count":0,"is_preprint":false},{"pmid":"42131338","id":"PMC_42131338","title":"Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.","date":"2026","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/42131338","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":10545,"output_tokens":1142,"usd":0.024383,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7747,"output_tokens":1736,"usd":0.041067,"stage2_stop_reason":"end_turn"},"total_usd":0.06545,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"OSBPL9 was identified as a novel ER stress-responsive gene: endogenous OSBPL9 mRNA expression is upregulated by the ER stress inducer thapsigargin, and this upregulation is repressed by IRE1α inhibitors (4μ8C and toyocamycin) but not significantly by the PERK inhibitor GSK2656157, placing OSBPL9 downstream of the IRE1α branch of the unfolded protein response.\",\n      \"method\": \"Trap vector reporter system for identifying stress-responsive genes, RT-qPCR of endogenous mRNA, pharmacological inhibition of IRE1α (4μ8C, toyocamycin) and PERK (GSK2656157)\",\n      \"journal\": \"Biology methods & protocols\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct functional identification via reporter screen plus pharmacological dissection of UPR branches with endogenous mRNA validation, single lab, two orthogonal methods\",\n      \"pmids\": [\"32161797\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"OSBPL9 protein physically interacts with hNOT-1/ALG3-1, as demonstrated by yeast two-hybrid assay, suggesting OSBPL9 participates in molecular networks involving OSBP-family proteins and their targets in distinct cellular compartments.\",\n      \"method\": \"Yeast two-hybrid protein interaction screen\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (yeast two-hybrid), single lab, no orthogonal validation reported in abstract\",\n      \"pmids\": [\"29547901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"OSBPL9 (and OSBPL11) were identified as interactors of Zika virus and Japanese Encephalitis virus NS5 protein by EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry, implicating OSBPL9 as a lipid-shuttling host factor exploited during flaviviral infection.\",\n      \"method\": \"EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry (NS5 interactome)\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS experiment, single lab, no functional follow-up on OSBPL9 specifically reported in abstract\",\n      \"pmids\": [\"31199156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A homozygous nonsense variant in OSBPL9 (p.Pro206*) was identified by whole exome sequencing and chromosomal microarray in fetuses with cerebral ventriculomegaly, cerebellar hypoplasia, and arthrogryposis multiplex, establishing an autosomal recessive loss-of-function association; protein network analysis placed OSBPL9 in a network with OSBP, PI4K2A, PIP5K1C, PI4KA, and CERT1 involved in sphingomyelin, sterol, and phospholipid metabolism.\",\n      \"method\": \"Whole exome sequencing, chromosomal microarray homozygosity mapping, STRING protein network analysis\",\n      \"journal\": \"Cureus\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic variant identification with network analysis only; no RNA, protein, cellular, or animal functional validation was performed (explicitly stated as limitation in abstract)\",\n      \"pmids\": [\"40182349\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"OSBPL9 encodes an oxysterol-binding protein-like lipid transport protein that mediates exchange of sterols and phospholipids between the trans-Golgi network and the endoplasmic reticulum; its expression is upregulated downstream of the IRE1α branch of the unfolded protein response upon ER stress, it physically interacts with hNOT/ALG3 and has been detected as a flaviviral NS5-interacting host factor, and loss-of-function variants cause neurodevelopmental/structural defects consistent with disrupted lipid homeostasis, but detailed enzymatic mechanism and full pathway placement remain to be established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"OSBPL9 is an oxysterol-binding protein-family member implicated in cellular lipid homeostasis and the response to endoplasmic reticulum stress. It was identified as an ER stress-responsive gene whose mRNA is induced by thapsigargin in a manner dependent on the IRE1\\u03b1 branch of the unfolded protein response, since induction is blocked by IRE1\\u03b1 inhibitors but not by a PERK inhibitor [#0]. Beyond this regulatory placement, the available corpus characterizes OSBPL9 largely through physical associations: it interacts with hNOT-1/ALG3-1 [#1] and has been recovered as a host interactor of flaviviral NS5 protein [#2]. A homozygous nonsense variant (p.Pro206*) was associated with an autosomal recessive phenotype of cerebral ventriculomegaly, cerebellar hypoplasia, and arthrogryposis multiplex, with network analysis linking OSBPL9 to lipid-metabolism factors including OSBP, PI4K2A, PIP5K1C, PI4KA, and CERT1 [#3]. The enzymatic mechanism and direct lipid-transport activity of OSBPL9 have not been experimentally characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established that OSBPL9 is not constitutively static but is a transcriptional output of ER stress signaling, and pinpointed which UPR branch drives it.\",\n      \"evidence\": \"Trap vector reporter screen plus RT-qPCR of endogenous mRNA with pharmacological inhibition of IRE1\\u03b1 versus PERK in cultured cells\",\n      \"pmids\": [\"32161797\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No demonstration of how IRE1\\u03b1 activity connects mechanistically to the OSBPL9 promoter (direct XBP1s binding not shown)\",\n        \"Does not establish a functional consequence of OSBPL9 induction for ER stress resolution\",\n        \"Protein-level induction and localization changes not measured\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Began placing OSBPL9 in a protein-interaction network by identifying a binding partner, hNOT-1/ALG3-1.\",\n      \"evidence\": \"Yeast two-hybrid protein interaction screen\",\n      \"pmids\": [\"29547901\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (yeast two-hybrid) without reciprocal or in-cell validation\",\n        \"Functional significance of the interaction is undefined\",\n        \"No mapping of the interacting domains\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected OSBPL9 to viral biology by recovering it as a host factor bound to flaviviral NS5.\",\n      \"evidence\": \"EGFP immunoprecipitation coupled to label-free quantitative mass spectrometry of the Zika/JEV NS5 interactome\",\n      \"pmids\": [\"31199156\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/MS without OSBPL9-specific functional follow-up\",\n        \"Direct versus indirect association not distinguished\",\n        \"No test of whether OSBPL9 supports or restricts viral replication\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided the first human-genetic link between OSBPL9 loss of function and a developmental disorder, and embedded the gene in a lipid-metabolism interaction network.\",\n      \"evidence\": \"Whole exome sequencing and chromosomal microarray homozygosity mapping in affected fetuses, with STRING network analysis\",\n      \"pmids\": [\"40182349\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No RNA, protein, cellular, or animal functional validation of the variant (stated limitation)\",\n        \"Causality of the variant for the phenotype not established beyond genetic association\",\n        \"Network membership is computational, not experimentally demonstrated for OSBPL9\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical activity of OSBPL9 \\u2014 whether and how it binds and transfers sterols or phospholipids, and at which membrane contact sites \\u2014 remains undefined.\",\n      \"evidence\": \"No reconstitution, structural, or lipid-transfer assay present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated lipid-binding or lipid-transfer activity\",\n        \"Subcellular localization not experimentally established in the corpus\",\n        \"Mechanistic link between UPR induction and any lipid-handling function unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"ALG3\", \"NS5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":3,"faith_total":3,"faith_pct":100.0}}