{"gene":"BET1","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":1990,"finding":"BET1 is required for transport from the endoplasmic reticulum to the Golgi complex in Saccharomyces cerevisiae. Genetic epistasis showed that BET1 interacts with BOS1 and SEC22: overproduction of BET1 suppresses sec22-3 growth and secretory defects, and a bet1 sec22 double mutant is inviable, placing these genes in the same essential ER-to-Golgi transport pathway. BET1 and BOS1 are not functionally equivalent, as BOS1 overproduction cannot rescue bet1 null lethality.","method":"Genetic suppression/epistasis analysis (multicopy suppression, double-mutant lethality) in S. cerevisiae","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic epistasis with multiple allele combinations replicated across several gene pairs, establishing pathway position","pmids":["2192256"],"is_preprint":false},{"year":2001,"finding":"Mammalian Bet1 forms a SNARE complex with Ykt6, syntaxin 5, and GS28, as demonstrated by co-immunoprecipitation. This complex participates in a late stage of ER-to-Golgi transport, as inhibition of Ykt6 (which associates with Bet1) blocks VSVG transport after the EGTA-sensitive stage and causes accumulation of cargo in peri-Golgi vesicular structures.","method":"Co-immunoprecipitation with specific antibodies; in vitro ER-Golgi transport assay with antibody inhibition and recombinant protein inhibition","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus functional in vitro transport assay with two orthogonal inhibition approaches in a single study","pmids":["11323436"],"is_preprint":false},{"year":2019,"finding":"In invasive cancer cells, MT1-MMP recruits Bet1 away from its canonical ER-Golgi transport role: Bet1 localizes to MT1-MMP-positive endosomes and forms a novel SNARE complex with syntaxin 4 and endosomal SNAREs to promote MT1-MMP trafficking to invadopodia at the plasma membrane. Bet1 also facilitates MT1-MMP export from raft-like ER structures at an early stage.","method":"Fluorescence co-localization, co-immunoprecipitation of SNARE complex components, loss-of-function analysis with trafficking readout","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus localization plus functional trafficking assay, single lab","pmids":["31519727"],"is_preprint":false},{"year":2021,"finding":"BET1 functions together with its SNARE complex partners GOSR2, SEC22b, and Syntaxin-5 for fusion of ER-derived vesicles with the ERGIC and cis-Golgi. Loss-of-function BET1 variants cause impaired ER-to-Golgi transport. The p.(Ile51Ser) variant was shown by in silico modeling and co-immunoprecipitation to reduce binding to novel interaction partners including ERGIC-53, and endogenous co-IP confirmed a BET1/ERGIC-53 interaction at the ERGIC compartment. Patient-derived fibroblasts showed mislocalization of ERGIC-53 and, in p.(Ile51Ser) cells, mislocalization of mutant BET1 itself.","method":"Endogenous co-immunoprecipitation, in silico structural modeling, patient-derived fibroblast functional assays (transport assay, protein localization by immunofluorescence), splice/frameshift variant characterization","journal":"EMBO molecular medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — endogenous Co-IP validated interaction, patient-derived functional data with multiple orthogonal methods (transport assay, localization, protein level quantification) across two families","pmids":["34779586"],"is_preprint":false}],"current_model":"BET1 is a SNARE protein that forms a complex with GOSR2 (BOS1), SEC22b, Syntaxin-5, and Ykt6 to mediate fusion of ER-derived vesicles with the ERGIC and cis-Golgi; it also interacts with ERGIC-53 at the ERGIC compartment, and in invasive cells can be recruited by MT1-MMP into novel endosomal SNARE complexes containing syntaxin 4 to facilitate MT1-MMP trafficking to invadopodia."},"narrative":{"mechanistic_narrative":"BET1 is a SNARE protein that mediates the fusion of ER-derived vesicles with the ERGIC and cis-Golgi during ER-to-Golgi transport [PMID:2192256, PMID:34779586]. It was first defined genetically in yeast, where it acts in an essential ER-to-Golgi pathway together with BOS1 and SEC22, with which it interacts non-redundantly [PMID:2192256]. In mammalian cells, BET1 assembles into a SNARE complex with syntaxin 5, Ykt6, and GS28 (GOSR1) to drive a late stage of ER-to-Golgi transport [PMID:11323436], and functions with GOSR2, SEC22b, and syntaxin 5 in vesicle fusion, additionally contacting ERGIC-53 at the ERGIC compartment [PMID:34779586]. Loss-of-function BET1 variants impair ER-to-Golgi transport and cause mislocalization of ERGIC-53, defining BET1 as the basis of a human disorder of ER-to-Golgi trafficking [PMID:34779586]. Beyond this canonical role, in invasive cancer cells MT1-MMP recruits BET1 to MT1-MMP-positive endosomes, where it forms a non-canonical SNARE complex with syntaxin 4 to promote MT1-MMP trafficking to invadopodia [PMID:31519727].","teleology":[{"year":1990,"claim":"Establishing that BET1 is a dedicated component of the ER-to-Golgi secretory pathway and acts in concert with specific partners answered where in trafficking this gene functions.","evidence":"Genetic suppression and double-mutant lethality analysis in S. cerevisiae","pmids":["2192256"],"confidence":"High","gaps":["Genetic epistasis does not establish physical complex membership or molecular activity","Does not define the mammalian orthologs or partners","No direct demonstration of vesicle fusion"]},{"year":2001,"claim":"Demonstrating that mammalian Bet1 physically assembles into a defined SNARE complex resolved its molecular mechanism as a fusion-mediating SNARE acting at a late ER-to-Golgi step.","evidence":"Co-immunoprecipitation and in vitro ER-Golgi transport assay with antibody and recombinant protein inhibition","pmids":["11323436"],"confidence":"High","gaps":["Stoichiometry and structural arrangement of the complex not resolved","Precise membrane (vesicle vs target) on which Bet1 resides not assigned","Regulation of complex assembly not addressed"]},{"year":2019,"claim":"Showing that MT1-MMP can divert Bet1 into a non-canonical endosomal SNARE complex established that BET1 has a context-dependent role beyond constitutive ER-to-Golgi transport.","evidence":"Fluorescence co-localization, co-IP of SNARE components, and loss-of-function trafficking readout in invasive cancer cells (single lab)","pmids":["31519727"],"confidence":"Medium","gaps":["Single-lab finding without independent replication","Mechanism of MT1-MMP-driven recruitment of Bet1 unknown","Generality across cancer types and physiological contexts unclear"]},{"year":2021,"claim":"Identifying loss-of-function BET1 variants in patients and the BET1/ERGIC-53 interaction connected the transport function to a human disease mechanism.","evidence":"Endogenous co-IP, in silico modeling, and patient-derived fibroblast transport and localization assays across two families","pmids":["34779586"],"confidence":"High","gaps":["Structural basis of the BET1/ERGIC-53 interaction not experimentally resolved","Full spectrum of clinical phenotype and genotype-phenotype correlation not defined","How variant-induced ERGIC-53 mislocalization produces pathology mechanistically unclear"]},{"year":null,"claim":"How BET1's canonical ER-to-Golgi function is balanced against its recruitment into alternative endosomal complexes, and the structural determinants of its complex assembly, remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of BET1-containing SNARE complexes in the corpus","Switch governing canonical vs MT1-MMP-associated function uncharacterized","Regulatory inputs controlling BET1 partner choice unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,3]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,3]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,3]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3]}],"complexes":["ER-to-Golgi SNARE complex (BET1/syntaxin 5/Ykt6/GS28)","BET1/GOSR2/SEC22b/syntaxin 5 SNARE complex","MT1-MMP endosomal SNARE complex (BET1/syntaxin 4)"],"partners":["GOSR2","SEC22B","STX5","YKT6","GOSR1","LMAN1","STX4","MMP14"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O15155","full_name":"BET1 homolog","aliases":["Golgi vesicular membrane-trafficking protein p18"],"length_aa":118,"mass_kda":13.3,"function":"Required for vesicular transport from the ER to the Golgi complex (PubMed:34779586). Functions as a SNARE involved in the docking process of ER-derived vesicles with the cis-Golgi membrane (By similarity)","subcellular_location":"Endoplasmic reticulum membrane; Golgi apparatus, cis-Golgi network membrane; Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/O15155/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/BET1","classification":"Common Essential","n_dependent_lines":428,"n_total_lines":1208,"dependency_fraction":0.3543046357615894},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000105829","cell_line_id":"CID000746","localizations":[{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"BET1;DKFZP781C0425","stoichiometry":10.0},{"gene":"NSF","stoichiometry":4.0},{"gene":"NAPA","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000746","total_profiled":1310},"omim":[{"mim_id":"615417","title":"BET1-LIKE PROTEIN; BET1L","url":"https://www.omim.org/entry/615417"},{"mim_id":"612442","title":"SEC22 HOMOLOG A, VESICLE TRAFFICKING PROTEIN; SEC22A","url":"https://www.omim.org/entry/612442"},{"mim_id":"605456","title":"BET1 GOLGI VESICULAR MEMBRANE-TRAFFICKING PROTEIN; BET1","url":"https://www.omim.org/entry/605456"},{"mim_id":"604029","title":"SEC22 HOMOLOG B, VESICLE TRAFFICKING PROTEIN; SEC22B","url":"https://www.omim.org/entry/604029"},{"mim_id":"604028","title":"SEC22 HOMOLOG C, VESICLE TRAFFICKING PROTEIN; SEC22C","url":"https://www.omim.org/entry/604028"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BET1"},"hgnc":{"alias_symbol":["hbet1"],"prev_symbol":[]},"alphafold":{"accession":"O15155","domains":[{"cath_id":"1.20.5","chopping":"22-91","consensus_level":"high","plddt":90.8877,"start":22,"end":91}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15155","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15155-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15155-F1-predicted_aligned_error_v6.png","plddt_mean":83.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BET1","jax_strain_url":"https://www.jax.org/strain/search?query=BET1"},"sequence":{"accession":"O15155","fasta_url":"https://rest.uniprot.org/uniprotkb/O15155.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15155/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15155"}},"corpus_meta":[{"pmid":"2192256","id":"PMC_2192256","title":"BET1, BOS1, and SEC22 are members of a group of interacting yeast genes required for transport from the endoplasmic reticulum to the Golgi complex.","date":"1990","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/2192256","citation_count":161,"is_preprint":false},{"pmid":"11323436","id":"PMC_11323436","title":"Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a late stage in endoplasmic reticulum-Golgi transport.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11323436","citation_count":113,"is_preprint":false},{"pmid":"20181741","id":"PMC_20181741","title":"Double bromodomain protein BET-1 and MYST HATs establish and maintain stable cell fates in C. elegans.","date":"2010","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/20181741","citation_count":21,"is_preprint":false},{"pmid":"31519727","id":"PMC_31519727","title":"MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane.","date":"2019","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31519727","citation_count":19,"is_preprint":false},{"pmid":"34779586","id":"PMC_34779586","title":"BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy.","date":"2021","source":"EMBO molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34779586","citation_count":14,"is_preprint":false},{"pmid":"36404134","id":"PMC_36404134","title":"Large-scale genetic screens identify BET-1 as a cytoskeleton regulator promoting actin function and life span.","date":"2022","source":"Aging cell","url":"https://pubmed.ncbi.nlm.nih.gov/36404134","citation_count":13,"is_preprint":false},{"pmid":"24285704","id":"PMC_24285704","title":"Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation.","date":"2013","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/24285704","citation_count":7,"is_preprint":false},{"pmid":"24349540","id":"PMC_24349540","title":"An RNAi-based dimorphic genetic screen identified the double bromodomain protein BET-1 as a sumo-dependent attenuator of RAS-mediated signalling.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24349540","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5999,"output_tokens":1532,"usd":0.020488,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7918,"output_tokens":2154,"usd":0.04672,"stage2_stop_reason":"end_turn"},"total_usd":0.067208,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully classify these papers before extracting discoveries.\n\n**Classification:**\n- Papers 1, 2, 4, 5: About the yeast/mammalian BET1 SNARE protein involved in ER-Golgi transport → INCLUDE (canonical BET1 / hbet1)\n- Papers 3, 6, 7, 8: About C. elegans BET-1, a **double bromodomain protein** — this is clearly a different protein (bromodomain-containing, regulates chromatin/actin/RAS signaling). This is a **symbol collision** — the C. elegans BET-1 bromodomain protein is not the ortholog of human BET1 (a SNARE protein). The corpus is predominantly about a SNARE protein; these C. elegans bromodomain papers describe a fundamentally incompatible function/domain architecture → EXCLUDE as symbol collision.\n\nNow extracting from papers 1, 2, 4, 5:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1990,\n      \"finding\": \"BET1 is required for transport from the endoplasmic reticulum to the Golgi complex in Saccharomyces cerevisiae. Genetic epistasis showed that BET1 interacts with BOS1 and SEC22: overproduction of BET1 suppresses sec22-3 growth and secretory defects, and a bet1 sec22 double mutant is inviable, placing these genes in the same essential ER-to-Golgi transport pathway. BET1 and BOS1 are not functionally equivalent, as BOS1 overproduction cannot rescue bet1 null lethality.\",\n      \"method\": \"Genetic suppression/epistasis analysis (multicopy suppression, double-mutant lethality) in S. cerevisiae\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic epistasis with multiple allele combinations replicated across several gene pairs, establishing pathway position\",\n      \"pmids\": [\"2192256\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Mammalian Bet1 forms a SNARE complex with Ykt6, syntaxin 5, and GS28, as demonstrated by co-immunoprecipitation. This complex participates in a late stage of ER-to-Golgi transport, as inhibition of Ykt6 (which associates with Bet1) blocks VSVG transport after the EGTA-sensitive stage and causes accumulation of cargo in peri-Golgi vesicular structures.\",\n      \"method\": \"Co-immunoprecipitation with specific antibodies; in vitro ER-Golgi transport assay with antibody inhibition and recombinant protein inhibition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus functional in vitro transport assay with two orthogonal inhibition approaches in a single study\",\n      \"pmids\": [\"11323436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In invasive cancer cells, MT1-MMP recruits Bet1 away from its canonical ER-Golgi transport role: Bet1 localizes to MT1-MMP-positive endosomes and forms a novel SNARE complex with syntaxin 4 and endosomal SNAREs to promote MT1-MMP trafficking to invadopodia at the plasma membrane. Bet1 also facilitates MT1-MMP export from raft-like ER structures at an early stage.\",\n      \"method\": \"Fluorescence co-localization, co-immunoprecipitation of SNARE complex components, loss-of-function analysis with trafficking readout\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus localization plus functional trafficking assay, single lab\",\n      \"pmids\": [\"31519727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"BET1 functions together with its SNARE complex partners GOSR2, SEC22b, and Syntaxin-5 for fusion of ER-derived vesicles with the ERGIC and cis-Golgi. Loss-of-function BET1 variants cause impaired ER-to-Golgi transport. The p.(Ile51Ser) variant was shown by in silico modeling and co-immunoprecipitation to reduce binding to novel interaction partners including ERGIC-53, and endogenous co-IP confirmed a BET1/ERGIC-53 interaction at the ERGIC compartment. Patient-derived fibroblasts showed mislocalization of ERGIC-53 and, in p.(Ile51Ser) cells, mislocalization of mutant BET1 itself.\",\n      \"method\": \"Endogenous co-immunoprecipitation, in silico structural modeling, patient-derived fibroblast functional assays (transport assay, protein localization by immunofluorescence), splice/frameshift variant characterization\",\n      \"journal\": \"EMBO molecular medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — endogenous Co-IP validated interaction, patient-derived functional data with multiple orthogonal methods (transport assay, localization, protein level quantification) across two families\",\n      \"pmids\": [\"34779586\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BET1 is a SNARE protein that forms a complex with GOSR2 (BOS1), SEC22b, Syntaxin-5, and Ykt6 to mediate fusion of ER-derived vesicles with the ERGIC and cis-Golgi; it also interacts with ERGIC-53 at the ERGIC compartment, and in invasive cells can be recruited by MT1-MMP into novel endosomal SNARE complexes containing syntaxin 4 to facilitate MT1-MMP trafficking to invadopodia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BET1 is a SNARE protein that mediates the fusion of ER-derived vesicles with the ERGIC and cis-Golgi during ER-to-Golgi transport [#0, #3]. It was first defined genetically in yeast, where it acts in an essential ER-to-Golgi pathway together with BOS1 and SEC22, with which it interacts non-redundantly [#0]. In mammalian cells, BET1 assembles into a SNARE complex with syntaxin 5, Ykt6, and GS28 (GOSR1) to drive a late stage of ER-to-Golgi transport [#1], and functions with GOSR2, SEC22b, and syntaxin 5 in vesicle fusion, additionally contacting ERGIC-53 at the ERGIC compartment [#3]. Loss-of-function BET1 variants impair ER-to-Golgi transport and cause mislocalization of ERGIC-53, defining BET1 as the basis of a human disorder of ER-to-Golgi trafficking [#3]. Beyond this canonical role, in invasive cancer cells MT1-MMP recruits BET1 to MT1-MMP-positive endosomes, where it forms a non-canonical SNARE complex with syntaxin 4 to promote MT1-MMP trafficking to invadopodia [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Establishing that BET1 is a dedicated component of the ER-to-Golgi secretory pathway and acts in concert with specific partners answered where in trafficking this gene functions.\",\n      \"evidence\": \"Genetic suppression and double-mutant lethality analysis in S. cerevisiae\",\n      \"pmids\": [\"2192256\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Genetic epistasis does not establish physical complex membership or molecular activity\",\n        \"Does not define the mammalian orthologs or partners\",\n        \"No direct demonstration of vesicle fusion\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Demonstrating that mammalian Bet1 physically assembles into a defined SNARE complex resolved its molecular mechanism as a fusion-mediating SNARE acting at a late ER-to-Golgi step.\",\n      \"evidence\": \"Co-immunoprecipitation and in vitro ER-Golgi transport assay with antibody and recombinant protein inhibition\",\n      \"pmids\": [\"11323436\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and structural arrangement of the complex not resolved\",\n        \"Precise membrane (vesicle vs target) on which Bet1 resides not assigned\",\n        \"Regulation of complex assembly not addressed\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that MT1-MMP can divert Bet1 into a non-canonical endosomal SNARE complex established that BET1 has a context-dependent role beyond constitutive ER-to-Golgi transport.\",\n      \"evidence\": \"Fluorescence co-localization, co-IP of SNARE components, and loss-of-function trafficking readout in invasive cancer cells (single lab)\",\n      \"pmids\": [\"31519727\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab finding without independent replication\",\n        \"Mechanism of MT1-MMP-driven recruitment of Bet1 unknown\",\n        \"Generality across cancer types and physiological contexts unclear\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying loss-of-function BET1 variants in patients and the BET1/ERGIC-53 interaction connected the transport function to a human disease mechanism.\",\n      \"evidence\": \"Endogenous co-IP, in silico modeling, and patient-derived fibroblast transport and localization assays across two families\",\n      \"pmids\": [\"34779586\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the BET1/ERGIC-53 interaction not experimentally resolved\",\n        \"Full spectrum of clinical phenotype and genotype-phenotype correlation not defined\",\n        \"How variant-induced ERGIC-53 mislocalization produces pathology mechanistically unclear\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How BET1's canonical ER-to-Golgi function is balanced against its recruitment into alternative endosomal complexes, and the structural determinants of its complex assembly, remain open.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of BET1-containing SNARE complexes in the corpus\",\n        \"Switch governing canonical vs MT1-MMP-associated function uncharacterized\",\n        \"Regulatory inputs controlling BET1 partner choice unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"ER-to-Golgi SNARE complex (BET1/syntaxin 5/Ykt6/GS28)\",\n      \"BET1/GOSR2/SEC22b/syntaxin 5 SNARE complex\",\n      \"MT1-MMP endosomal SNARE complex (BET1/syntaxin 4)\"\n    ],\n    \"partners\": [\n      \"GOSR2\",\n      \"SEC22B\",\n      \"STX5\",\n      \"YKT6\",\n      \"GOSR1\",\n      \"LMAN1\",\n      \"STX4\",\n      \"MMP14\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}