{"gene":"SNX7","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2020,"finding":"SNX7 forms functional heterodimers with SNX4 (and SNX30) that associate with tubulovesicular endocytic membranes; the SNX4-SNX7 heterodimer is an autophagy-specific complex required for efficient recruitment and/or retention of core autophagy regulators at the nascent isolation membrane and coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites.","method":"siRNA knockdown, CRISPR-Cas9 knockout, image-based analysis of autophagosome assembly, co-immunoprecipitation/heterodimerization assays, co-localization with ATG9A-positive membranes","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP establishing heterodimer, CRISPR KO with defined cellular autophagy phenotype, multiple orthogonal methods (siRNA, CRISPR, imaging) in one study","pmids":["32513819"],"is_preprint":false},{"year":2012,"finding":"SNX7 knockdown in zebrafish hepatoblasts activates the c-FLIP/caspase-8 apoptotic pathway, leading to massive hepatoblast apoptosis during early liver budding; overexpression of c-FLIP(S) rescues the liver defect caused by SNX7 knockdown, establishing SNX7 as an antiapoptotic regulator that suppresses caspase-8 activation via c-FLIP.","method":"Morpholino knockdown in zebrafish, siRNA knockdown in cell culture, rescue by c-FLIP(S) overexpression, apoptosis assays","journal":"Hepatology (Baltimore, Md.)","confidence":"High","confidence_rationale":"Tier 2 / Moderate — morpholino KD with defined in vivo phenotype, cell culture confirmation, pathway placement by genetic rescue experiment","pmids":["22213104"],"is_preprint":false},{"year":2015,"finding":"Reduced SNX7 expression leads to a caspase-8-driven activation of interleukin-1β, which subsequently induces the brain kynurenine pathway enzyme TDO2, increasing kynurenic acid production in glia.","method":"Post-mortem brain tissue analysis and in vitro experiments (cell culture with SNX7 downregulation, measurement of caspase-8 activation, IL-1β levels, and TDO2 induction)","journal":"Molecular psychiatry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — in vitro cell experiments and post-mortem tissue, single lab, pathway placement supported but methods not fully detailed in abstract","pmids":["26666201"],"is_preprint":false},{"year":2017,"finding":"Overexpression of SNX7 in HEK293T cells reduces steady-state and cell-surface APP levels and decreases secreted Aβ and sAPPβ; this reduction is prevented by lysosomal inhibitors (NH4Cl, Bafilomycin A1), indicating SNX7 directs APP to lysosomal degradation. No change in BACE1 surface distribution or steady-state levels was observed upon SNX7 overexpression.","method":"Overexpression in HEK293T cells, ELISA for Aβ/sAPPβ, surface biotinylation, lysosomal inhibitor treatment (NH4Cl, Bafilomycin A1)","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — defined cellular mechanism with pharmacological pathway placement, single lab, single overexpression approach","pmids":["29080748"],"is_preprint":false},{"year":2014,"finding":"Recombinant human SNX7 PX-BAR domain fragment binds phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 in vitro, and the protein is homogeneous in solution.","method":"Recombinant protein expression and purification from E. coli, lipid overlay assay, dynamic light scattering","journal":"Sheng wu gong cheng xue bao = Chinese journal of biotechnology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro biochemical binding assay with purified recombinant protein, single lab, single method","pmids":["25720158"],"is_preprint":false},{"year":2025,"finding":"SNX7 overexpression in prostate cancer cells activates CFLIP expression, which in turn weakens the interaction between ATG3 and LC3A, thereby inhibiting autophagy; CFLIP knockdown enhanced ATG3-LC3A binding and SNX7 overexpression reversed this effect.","method":"Cell overexpression/knockdown experiments, co-immunoprecipitation of ATG3 and LC3A, rescue experiments, cell viability/migration/invasion assays","journal":"Discover oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — Co-IP establishing protein-protein interaction change, rescue experiment placing SNX7 upstream of CFLIP-ATG3-LC3 axis, single lab","pmids":["40883630"],"is_preprint":false}],"current_model":"SNX7 is a SNX-BAR family peripheral membrane protein that (1) forms an autophagy-specific heterodimer with SNX4 to coordinate ATG9A trafficking and autophagosome assembly at endocytic membranes; (2) suppresses apoptosis by inhibiting the c-FLIP/caspase-8 pathway; (3) directs APP to lysosomal degradation to reduce Aβ production; (4) activates CFLIP expression to inhibit autophagy by weakening ATG3-LC3A interaction in cancer cells; and (5) binds phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 via its PX domain, consistent with its role in endosomal membrane association."},"narrative":{"mechanistic_narrative":"SNX7 is a sorting nexin that operates at endocytic membranes to control protein trafficking, autophagy, and cell survival [PMID:32513819, PMID:22213104]. Its PX-BAR module binds the phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3, consistent with peripheral association with endosomal membranes [PMID:25720158]. SNX7 forms an autophagy-specific heterodimer with SNX4 (and SNX30) on tubulovesicular endocytic membranes, where it coordinates ATG9A trafficking and the recruitment of core autophagy regulators to establish productive autophagosome assembly sites [PMID:32513819]. In a cargo-sorting role, SNX7 directs amyloid precursor protein (APP) to lysosomal degradation, lowering steady-state and cell-surface APP and reducing secreted Aβ and sAPPβ without altering BACE1 [PMID:29080748]. SNX7 also acts as an antiapoptotic regulator: it suppresses caspase-8 activation through c-FLIP, and its loss drives caspase-8-dependent hepatoblast apoptosis that is rescued by c-FLIP(S) [PMID:22213104]. In prostate cancer cells, SNX7 overexpression activates CFLIP, which weakens the ATG3–LC3A interaction and thereby inhibits autophagy [PMID:40883630].","teleology":[{"year":2012,"claim":"Established SNX7 as an antiapoptotic regulator by showing its loss activates the caspase-8 pathway, addressing whether this sorting nexin has a role in cell survival.","evidence":"Morpholino knockdown in zebrafish hepatoblasts with siRNA confirmation in culture and genetic rescue by c-FLIP(S) overexpression","pmids":["22213104"],"confidence":"High","gaps":["Does not define how SNX7 mechanistically suppresses caspase-8/c-FLIP at the molecular level","Membrane/trafficking basis of the antiapoptotic effect not connected"]},{"year":2014,"claim":"Defined the lipid-binding specificity of the SNX7 PX-BAR domain, providing the biochemical basis for membrane association.","evidence":"Recombinant human PX-BAR fragment from E. coli tested by lipid overlay assay and dynamic light scattering","pmids":["25720158"],"confidence":"Medium","gaps":["In vitro lipid overlay does not establish in-cell membrane targeting","No structural model of the membrane-bound complex"]},{"year":2015,"claim":"Linked reduced SNX7 to a caspase-8/IL-1β/TDO2 cascade in glia, extending the antiapoptotic axis to downstream neuroinflammatory signaling.","evidence":"Post-mortem brain tissue analysis with in vitro SNX7 downregulation and measurement of caspase-8, IL-1β, and TDO2","pmids":["26666201"],"confidence":"Medium","gaps":["Causal chain from SNX7 to TDO2 not reconstituted","Single lab, abstract-level methods"]},{"year":2017,"claim":"Showed SNX7 functions as a cargo sorter directing APP to lysosomal degradation, providing a trafficking mechanism with implications for Aβ production.","evidence":"Overexpression in HEK293T cells with ELISA for Aβ/sAPPβ, surface biotinylation, and lysosomal inhibitor treatment","pmids":["29080748"],"confidence":"Medium","gaps":["Single overexpression approach without loss-of-function confirmation","Direct SNX7-APP interaction not demonstrated"]},{"year":2020,"claim":"Identified the SNX4-SNX7 heterodimer as an autophagy-specific complex coordinating ATG9A trafficking, defining SNX7's core trafficking function.","evidence":"siRNA knockdown, CRISPR-Cas9 knockout, reciprocal co-IP, and image-based analysis of autophagosome assembly and ATG9A co-localization","pmids":["32513819"],"confidence":"High","gaps":["Precise step at which ATG9A trafficking is controlled not resolved","How phosphoinositide binding directs heterodimer to autophagy membranes not established"]},{"year":2025,"claim":"Connected SNX7 to autophagy inhibition in cancer via a CFLIP-ATG3-LC3A axis, in apparent contrast to its autophagy-promoting role in the SNX4 heterodimer.","evidence":"Overexpression/knockdown in prostate cancer cells with co-IP of ATG3 and LC3A and rescue experiments","pmids":["40883630"],"confidence":"Medium","gaps":["Single lab, single cancer context","Does not reconcile autophagy-promoting versus autophagy-inhibiting roles of SNX7"]},{"year":null,"claim":"How SNX7's phosphoinositide-binding membrane activity is mechanistically coupled to its divergent roles in autophagy, cargo lysosomal sorting, and apoptosis suppression remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model linking lipid binding to cargo selection","Opposing autophagy effects (SNX4 heterodimer vs CFLIP-ATG3-LC3A) not integrated","Direct substrate/cargo interactions largely undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[0,5]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[1]}],"complexes":["SNX4-SNX7 heterodimer"],"partners":["SNX4","SNX30"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UNH6","full_name":"Sorting nexin-7","aliases":[],"length_aa":387,"mass_kda":45.3,"function":"Involved in the regulation of endocytosis and in several stages of intracellular trafficking (PubMed:32513819). Together with SNX4, involved in autophagosome assembly by regulating trafficking and recycling of phospholipid scramblase ATG9A (PubMed:32513819)","subcellular_location":"Early endosome membrane","url":"https://www.uniprot.org/uniprotkb/Q9UNH6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SNX7","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000162627","cell_line_id":"CID000684","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"SNX4","stoichiometry":10.0},{"gene":"PLIN2","stoichiometry":0.2},{"gene":"FANCL","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000684","total_profiled":1310},"omim":[{"mim_id":"620955","title":"SORTING NEXIN 30; 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many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNX7"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9UNH6","domains":[{"cath_id":"3.30.1520.10","chopping":"30-151","consensus_level":"medium","plddt":91.0124,"start":30,"end":151},{"cath_id":"1.20.1270.60","chopping":"180-387","consensus_level":"medium","plddt":92.132,"start":180,"end":387}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UNH6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UNH6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UNH6-F1-predicted_aligned_error_v6.png","plddt_mean":85.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNX7","jax_strain_url":"https://www.jax.org/strain/search?query=SNX7"},"sequence":{"accession":"Q9UNH6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UNH6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UNH6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UNH6"}},"corpus_meta":[{"pmid":"27245499","id":"PMC_27245499","title":"The kynurenine pathway in schizophrenia and bipolar disorder.","date":"2016","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/27245499","citation_count":217,"is_preprint":false},{"pmid":"26666201","id":"PMC_26666201","title":"A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder.","date":"2015","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/26666201","citation_count":86,"is_preprint":false},{"pmid":"32513819","id":"PMC_32513819","title":"A heterodimeric SNX4--SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/32513819","citation_count":37,"is_preprint":false},{"pmid":"16130112","id":"PMC_16130112","title":"New locus for hereditary spastic paraplegia maps to chromosome 1p31.1-1p21.1.","date":"2005","source":"Annals of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/16130112","citation_count":23,"is_preprint":false},{"pmid":"22213104","id":"PMC_22213104","title":"An antiapoptotic role of sorting nexin 7 is required for liver development in zebrafish.","date":"2012","source":"Hepatology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/22213104","citation_count":18,"is_preprint":false},{"pmid":"18273836","id":"PMC_18273836","title":"High definition cytogenetics and oligonucleotide aCGH analyses of cisplatin-resistant ovarian cancer cells.","date":"2008","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/18273836","citation_count":17,"is_preprint":false},{"pmid":"29080748","id":"PMC_29080748","title":"Overexpression of SNX7 reduces Aβ production by enhancing lysosomal degradation of APP.","date":"2017","source":"Biochemical and biophysical research 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productive autophagosome assembly sites.\",\n      \"method\": \"siRNA knockdown, CRISPR-Cas9 knockout, image-based analysis of autophagosome assembly, co-immunoprecipitation/heterodimerization assays, co-localization with ATG9A-positive membranes\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP establishing heterodimer, CRISPR KO with defined cellular autophagy phenotype, multiple orthogonal methods (siRNA, CRISPR, imaging) in one study\",\n      \"pmids\": [\"32513819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"SNX7 knockdown in zebrafish hepatoblasts activates the c-FLIP/caspase-8 apoptotic pathway, leading to massive hepatoblast apoptosis during early liver budding; overexpression of c-FLIP(S) rescues the liver defect caused by SNX7 knockdown, establishing SNX7 as an antiapoptotic regulator that suppresses caspase-8 activation via c-FLIP.\",\n      \"method\": \"Morpholino knockdown in zebrafish, siRNA knockdown in cell culture, rescue by c-FLIP(S) overexpression, apoptosis assays\",\n      \"journal\": \"Hepatology (Baltimore, Md.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino KD with defined in vivo phenotype, cell culture confirmation, pathway placement by genetic rescue experiment\",\n      \"pmids\": [\"22213104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Reduced SNX7 expression leads to a caspase-8-driven activation of interleukin-1β, which subsequently induces the brain kynurenine pathway enzyme TDO2, increasing kynurenic acid production in glia.\",\n      \"method\": \"Post-mortem brain tissue analysis and in vitro experiments (cell culture with SNX7 downregulation, measurement of caspase-8 activation, IL-1β levels, and TDO2 induction)\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — in vitro cell experiments and post-mortem tissue, single lab, pathway placement supported but methods not fully detailed in abstract\",\n      \"pmids\": [\"26666201\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Overexpression of SNX7 in HEK293T cells reduces steady-state and cell-surface APP levels and decreases secreted Aβ and sAPPβ; this reduction is prevented by lysosomal inhibitors (NH4Cl, Bafilomycin A1), indicating SNX7 directs APP to lysosomal degradation. No change in BACE1 surface distribution or steady-state levels was observed upon SNX7 overexpression.\",\n      \"method\": \"Overexpression in HEK293T cells, ELISA for Aβ/sAPPβ, surface biotinylation, lysosomal inhibitor treatment (NH4Cl, Bafilomycin A1)\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — defined cellular mechanism with pharmacological pathway placement, single lab, single overexpression approach\",\n      \"pmids\": [\"29080748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Recombinant human SNX7 PX-BAR domain fragment binds phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 in vitro, and the protein is homogeneous in solution.\",\n      \"method\": \"Recombinant protein expression and purification from E. coli, lipid overlay assay, dynamic light scattering\",\n      \"journal\": \"Sheng wu gong cheng xue bao = Chinese journal of biotechnology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro biochemical binding assay with purified recombinant protein, single lab, single method\",\n      \"pmids\": [\"25720158\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SNX7 overexpression in prostate cancer cells activates CFLIP expression, which in turn weakens the interaction between ATG3 and LC3A, thereby inhibiting autophagy; CFLIP knockdown enhanced ATG3-LC3A binding and SNX7 overexpression reversed this effect.\",\n      \"method\": \"Cell overexpression/knockdown experiments, co-immunoprecipitation of ATG3 and LC3A, rescue experiments, cell viability/migration/invasion assays\",\n      \"journal\": \"Discover oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — Co-IP establishing protein-protein interaction change, rescue experiment placing SNX7 upstream of CFLIP-ATG3-LC3 axis, single lab\",\n      \"pmids\": [\"40883630\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNX7 is a SNX-BAR family peripheral membrane protein that (1) forms an autophagy-specific heterodimer with SNX4 to coordinate ATG9A trafficking and autophagosome assembly at endocytic membranes; (2) suppresses apoptosis by inhibiting the c-FLIP/caspase-8 pathway; (3) directs APP to lysosomal degradation to reduce Aβ production; (4) activates CFLIP expression to inhibit autophagy by weakening ATG3-LC3A interaction in cancer cells; and (5) binds phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 via its PX domain, consistent with its role in endosomal membrane association.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNX7 is a sorting nexin that operates at endocytic membranes to control protein trafficking, autophagy, and cell survival [#0, #1]. Its PX-BAR module binds the phosphoinositides PtdIns(5)P, PtdIns(4,5)P2, and PtdIns(3,4,5)P3, consistent with peripheral association with endosomal membranes [#4]. SNX7 forms an autophagy-specific heterodimer with SNX4 (and SNX30) on tubulovesicular endocytic membranes, where it coordinates ATG9A trafficking and the recruitment of core autophagy regulators to establish productive autophagosome assembly sites [#0]. In a cargo-sorting role, SNX7 directs amyloid precursor protein (APP) to lysosomal degradation, lowering steady-state and cell-surface APP and reducing secreted Aβ and sAPPβ without altering BACE1 [#3]. SNX7 also acts as an antiapoptotic regulator: it suppresses caspase-8 activation through c-FLIP, and its loss drives caspase-8-dependent hepatoblast apoptosis that is rescued by c-FLIP(S) [#1]. In prostate cancer cells, SNX7 overexpression activates CFLIP, which weakens the ATG3–LC3A interaction and thereby inhibits autophagy [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established SNX7 as an antiapoptotic regulator by showing its loss activates the caspase-8 pathway, addressing whether this sorting nexin has a role in cell survival.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish hepatoblasts with siRNA confirmation in culture and genetic rescue by c-FLIP(S) overexpression\",\n      \"pmids\": [\"22213104\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define how SNX7 mechanistically suppresses caspase-8/c-FLIP at the molecular level\", \"Membrane/trafficking basis of the antiapoptotic effect not connected\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the lipid-binding specificity of the SNX7 PX-BAR domain, providing the biochemical basis for membrane association.\",\n      \"evidence\": \"Recombinant human PX-BAR fragment from E. coli tested by lipid overlay assay and dynamic light scattering\",\n      \"pmids\": [\"25720158\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vitro lipid overlay does not establish in-cell membrane targeting\", \"No structural model of the membrane-bound complex\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Linked reduced SNX7 to a caspase-8/IL-1β/TDO2 cascade in glia, extending the antiapoptotic axis to downstream neuroinflammatory signaling.\",\n      \"evidence\": \"Post-mortem brain tissue analysis with in vitro SNX7 downregulation and measurement of caspase-8, IL-1β, and TDO2\",\n      \"pmids\": [\"26666201\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal chain from SNX7 to TDO2 not reconstituted\", \"Single lab, abstract-level methods\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed SNX7 functions as a cargo sorter directing APP to lysosomal degradation, providing a trafficking mechanism with implications for Aβ production.\",\n      \"evidence\": \"Overexpression in HEK293T cells with ELISA for Aβ/sAPPβ, surface biotinylation, and lysosomal inhibitor treatment\",\n      \"pmids\": [\"29080748\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single overexpression approach without loss-of-function confirmation\", \"Direct SNX7-APP interaction not demonstrated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified the SNX4-SNX7 heterodimer as an autophagy-specific complex coordinating ATG9A trafficking, defining SNX7's core trafficking function.\",\n      \"evidence\": \"siRNA knockdown, CRISPR-Cas9 knockout, reciprocal co-IP, and image-based analysis of autophagosome assembly and ATG9A co-localization\",\n      \"pmids\": [\"32513819\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise step at which ATG9A trafficking is controlled not resolved\", \"How phosphoinositide binding directs heterodimer to autophagy membranes not established\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected SNX7 to autophagy inhibition in cancer via a CFLIP-ATG3-LC3A axis, in apparent contrast to its autophagy-promoting role in the SNX4 heterodimer.\",\n      \"evidence\": \"Overexpression/knockdown in prostate cancer cells with co-IP of ATG3 and LC3A and rescue experiments\",\n      \"pmids\": [\"40883630\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single cancer context\", \"Does not reconcile autophagy-promoting versus autophagy-inhibiting roles of SNX7\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNX7's phosphoinositide-binding membrane activity is mechanistically coupled to its divergent roles in autophagy, cargo lysosomal sorting, and apoptosis suppression remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model linking lipid binding to cargo selection\", \"Opposing autophagy effects (SNX4 heterodimer vs CFLIP-ATG3-LC3A) not integrated\", \"Direct substrate/cargo interactions largely undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"SNX4-SNX7 heterodimer\"],\n    \"partners\": [\"SNX4\", \"SNX30\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}