{"gene":"TBC1D10A","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2001,"finding":"EPI64 (TBC1D10A) was identified as a TBC/RabGAP domain-containing microvillar protein that binds preferentially to the first PDZ domain of EBP50 and E3KARP via its C-terminal DTYL motif; mutation to DTYLA abolishes PDZ binding and microvillar localization.","method":"Affinity chromatography from placental microvilli, PDZ domain binding assays, site-directed mutagenesis, colocalization by immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (affinity chromatography, mutagenesis, colocalization), replicated in subsequent studies","pmids":["11285285"],"is_preprint":false},{"year":2006,"finding":"EPI64 (TBC1D10A) is a specific GTPase-activating protein (GAP) for Rab27A; it induces melanosome aggregation in melanocytes, traps GTP-Rab27A via the Slac2-a SHD effector domain in cells, and mutations in the catalytic TBC domain abolish GAP activity and melanosome aggregation.","method":"Functional screen of 40 TBC proteins in melanocytes (melanosome aggregation assay), GTP-Rab27A trapping assay, in vitro Rab27A-GAP activity assay, catalytic domain mutagenesis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro GAP assay plus mutagenesis plus cell-based functional assay; replicated in subsequent independent studies","pmids":["16923811"],"is_preprint":false},{"year":2006,"finding":"EPI64 (TBC1D10A) regulates microvillar structure: overexpression relocalizes EPI64 and EBP50 to the microvillar base; uncoupling EPI64 from EBP50, mislocalizing its TBC domain, or knockdown of EBP50 all result in loss of microvilli. The TBC domain of EPI64 binds directly to Arf6-GTP and overexpression of the TBC domain increases Arf6-GTP levels; expression of dominant-active Arf6 causes microvillar loss.","method":"High-resolution light microscopy, overexpression and dominant-negative constructs, siRNA knockdown, direct binding assay (TBC domain vs. Arf6-GTP), GTP-bound Arf6 measurements","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (imaging, binding assay, KD, OE with mutagenesis) in a single focused study","pmids":["17145964"],"is_preprint":false},{"year":2007,"finding":"TBC1D10A–C were identified in a screen of 39 human RabGAPs as specific regulators of Shiga toxin trafficking from the cell surface to the Golgi apparatus, without affecting EGF uptake.","method":"Genome-wide RabGAP overexpression screen; Shiga toxin and EGF trafficking assays in HeLa cells","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — screen-based identification with defined readout, but mechanistic details for TBC1D10A specifically are limited to this screen result","pmids":["17562788"],"is_preprint":false},{"year":2011,"finding":"EPI64 (TBC1D10A) acts as a physiological Rab27-GAP in rat parotid acinar cells: it localizes to the apical plasma membrane, an anti-TBC domain antibody blocks reduction of GTP-Rab27 in permeabilized cells and inhibits amylase release dose-dependently, and EPI64 expression increases upon isoproterenol stimulation to enhance amylase secretion.","method":"Subcellular fractionation, immunohistochemistry, streptolysin-O permeabilization with anti-EPI64 antibody inhibition, antisense oligonucleotide knockdown, amylase release assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal approaches (antibody inhibition, antisense KD, fractionation) in a physiologically relevant cell type, consistent with prior in vitro GAP data","pmids":["21832089"],"is_preprint":false},{"year":2012,"finding":"EPI64 (TBC1D10A) regulates Arf6-dependent membrane trafficking: expression induces actin-coated vacuoles (an Arf6-activation phenotype) dependent on its RabGAP activity; EPI64 lowers Rab8a-GTP levels and directly binds the Rab8a effector JFC1 via its C-terminal region to recruit Rab8a-GTP for deactivation, coordinating Arf6 and Rab8a membrane trafficking.","method":"Overexpression of wild-type and GAP-dead mutants, Rab8-GTP pull-down, direct binding assay (EPI64 C-terminus vs. JFC1), co-localization, mutant rescue experiments","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding assay, Rab8-GTP pull-down, and multiple mutant analyses providing mechanistic model in single focused study","pmids":["22219378"],"is_preprint":false},{"year":2012,"finding":"All three EPI64 subfamily members (EPI64A/TBC1D10A, EPI64B/TBC1D10B, EPI64C/TBC1D10C) possess RasGAP activity in vivo, as shown by FRET-based Ras activity sensors, Bos pull-down assay, and time-lapse FRET imaging. EPI64A and EPI64B localize predominantly to the cell periphery (plasma membrane).","method":"Spectrofluorometry with FRET sensors, Bos pull-down assay for active Ras, time-lapse confocal FRET imaging in COS-7 cells","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — three independent in-cell methods from a single lab; no in vitro reconstitution with purified proteins","pmids":["23248241"],"is_preprint":false},{"year":2015,"finding":"In pancreatic β-cells, EPI64 (TBC1D10A) interacts with the Arf6-GEF ARNO (CYTH2); glucose-induced PI3K activation generates PIP3 that recruits ARNO to the plasma membrane, which in turn recruits EPI64 to regulate the early stage of endocytosis following insulin secretion.","method":"Co-immunoprecipitation (EPI64 with ARNO), PI3K inhibition, glucose stimulation assays, endocytosis assays in pancreatic β-cells","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-IP identifies binding partner, multiple cell-based functional assays; single lab study","pmids":["26683831"],"is_preprint":false},{"year":2017,"finding":"TBC1D10A acts as a GAP for Rab35 in human endothelial cells: TBC1D10A overexpression inhibits histamine-evoked Weibel-Palade body exocytosis in a GAP-activity-dependent manner, Rab35 co-immunoprecipitates with TBC1D10A, and expression of the GAP-insensitive Rab35(Q67A) mutant rescues the inhibitory effect of TBC1D10A.","method":"Genome-wide RabGAP overexpression screen for WPB exocytosis, co-immunoprecipitation, GAP-dead mutant rescue, Rab35 dominant-negative and siRNA knockdown, von Willebrand factor and P-selectin secretion assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP, GAP-dead mutagenesis, dominant-negative and knockdown rescue all converge on the same conclusion in one study","pmids":["28566286"],"is_preprint":false},{"year":2017,"finding":"TBC1D10A (as a Rab35-GAP) inhibits Rab35-mediated recruitment of the autophagy receptor NDP52 to bacteria-containing endosomes and to damaged mitochondria, thereby negatively regulating xenophagy and mitophagy.","method":"Overexpression of TBC1D10A GAP, NDP52 recruitment assay to intracellular bacteria and damaged mitochondria, mitophagy and autophagosome maturation assays","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function and overexpression with defined autophagy readouts; single lab study","pmids":["28848034"],"is_preprint":false},{"year":2019,"finding":"TBC1D10A acts on RAB13 (in addition to Rab27A and Rab35), colocalizes with RAB13 and VEGFR2 in activated endothelial cells, and leads to increased Erk1/2 signaling, opposite to the effect of the paralog TBC1D10B on VEGFR2 signaling.","method":"RabGAP overexpression panel, colocalization imaging (TBC1D10A, RAB13, VEGFR2), Erk1/2 and p38 signaling assays, tube formation assay","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — colocalization-based RAB13 substrate inference from a single lab; no direct GAP activity assay for RAB13 reported in abstract","pmids":["31527750"],"is_preprint":false},{"year":2019,"finding":"TBC1D10A (GAP for Rab35) and the Rab35-GEF DENND1B both localize to cilia, and TBC1D10A regulates ciliary length and the ciliary localization of Rab35 in mammalian cells.","method":"siRNA knockdown, GFP-TBC1D10A live imaging/localization to cilia, cilium length measurements","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment tied to functional consequence (ciliary length), supported by KD phenotype; single lab","pmids":["31432619"],"is_preprint":false},{"year":2019,"finding":"IRR (insulin receptor-related receptor) was identified as an EPI64-interacting protein in pancreatic β-cells; knockdown of IRR inhibits glucose-induced endocytosis (transferrin uptake), ARNO membrane translocation, and PIP3 generation, placing IRR upstream of PI3K/PIP3 in the EPI64-regulated endocytosis pathway.","method":"Protein interaction identification (EPI64-interactor screen), siRNA knockdown of IRR, transferrin uptake assay, ARNO translocation assay, PIP3 measurement","journal":"Journal of pharmacological sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single identification method; abstract does not specify how EPI64–IRR interaction was detected","pmids":["31353211"],"is_preprint":false}],"current_model":"TBC1D10A (EPI64) is a TBC-domain-containing RabGAP that localizes to apical microvilli via its C-terminal DTYL motif binding to the PDZ domains of the scaffolding protein EBP50, where it stabilizes Arf6-GTP (by binding Arf6-GTP through its TBC domain), inactivates Rab27A/Rab27B (promoting secretory granule exocytosis), inactivates Rab35 (suppressing NDP52-mediated autophagy and regulating ciliary length and Weibel-Palade body exocytosis), inactivates Rab8a (by recruiting it via the Rab8a effector JFC1), and also possesses RasGAP activity; together these activities coordinate microvillar structure, membrane trafficking, secretion, and autophagy."},"narrative":{"mechanistic_narrative":"TBC1D10A (EPI64) is a TBC-domain RabGAP that couples microvillar architecture to membrane trafficking and regulated secretion at the apical plasma membrane [PMID:11285285, PMID:17145964]. It is targeted to microvilli through its C-terminal DTYL motif, which binds the first PDZ domain of the scaffold EBP50; uncoupling EPI64 from EBP50 or mislocalizing its TBC domain abolishes both its localization and the integrity of microvilli [PMID:11285285, PMID:17145964]. Through its catalytic TBC domain it functions as a GAP for multiple Rab GTPases—Rab27A, where it drives melanosome aggregation and, in parotid acinar cells, controls Rab27-dependent amylase exocytosis [PMID:16923811, PMID:21832089]; Rab35, where it suppresses histamine-evoked Weibel-Palade body exocytosis and negatively regulates NDP52-dependent xenophagy and mitophagy while controlling ciliary length and ciliary Rab35 localization [PMID:28566286, PMID:28848034, PMID:31432619]; and Rab8a, which it recruits for inactivation via the effector JFC1 [PMID:22219378]. In parallel its TBC domain binds and stabilizes Arf6-GTP, linking its GAP activity to Arf6-dependent actin-coated vacuole formation and microvillar remodeling [PMID:17145964, PMID:22219378]. In pancreatic β-cells EPI64 is recruited downstream of PI3K/PIP3 by the Arf6-GEF ARNO to regulate endocytosis following insulin secretion [PMID:26683831]. Beyond these Rab/Arf activities, EPI64 also exhibits RasGAP activity [PMID:23248241].","teleology":[{"year":2001,"claim":"Established how an uncharacterized microvillar TBC protein is targeted to its site of action, defining the scaffold interaction that anchors EPI64 to microvilli.","evidence":"Affinity chromatography from placental microvilli with PDZ binding assays and DTYL-motif mutagenesis","pmids":["11285285"],"confidence":"High","gaps":["Did not define a catalytic substrate or GAP target","Functional consequence of microvillar localization unresolved at this stage"]},{"year":2006,"claim":"Resolved the catalytic identity of EPI64 by showing its TBC domain is a specific Rab27A-GAP, linking it to organelle (melanosome) transport.","evidence":"TBC-protein functional screen in melanocytes, GTP-Rab27A trapping, in vitro Rab27A-GAP assay, and catalytic-domain mutagenesis","pmids":["16923811"],"confidence":"High","gaps":["Physiological relevance in secretory tissues not yet shown","Other potential Rab substrates not surveyed"]},{"year":2006,"claim":"Connected EPI64's GAP scaffold to microvillar structure and revealed a second small-GTPase activity, showing its TBC domain binds and elevates Arf6-GTP.","evidence":"High-resolution imaging, EBP50 knockdown, dominant constructs, and direct TBC-domain–Arf6-GTP binding/GTP-level assays","pmids":["17145964"],"confidence":"High","gaps":["Mechanism by which Arf6-GTP binding is reconciled with GAP catalysis unclear","Whether Arf6 binding requires Rab inactivation not resolved"]},{"year":2011,"claim":"Demonstrated that EPI64's Rab27-GAP activity is physiologically required for regulated exocytosis in a native secretory cell.","evidence":"Fractionation, anti-TBC antibody inhibition in permeabilized parotid acinar cells, antisense knockdown, and amylase release assays","pmids":["21832089"],"confidence":"High","gaps":["Upstream signals controlling EPI64 expression beyond isoproterenol not defined","Direct in vivo Rab27 GTP measurement in this tissue limited"]},{"year":2012,"claim":"Expanded the trafficking model by showing EPI64 inactivates Rab8a through effector-mediated recruitment, coordinating Arf6 and Rab8a pathways.","evidence":"GAP-dead overexpression, Rab8-GTP pull-down, and direct binding of the EPI64 C-terminus to JFC1","pmids":["22219378"],"confidence":"High","gaps":["Whether Rab8a recruitment via JFC1 occurs in physiological cell types untested","Relationship to Rab27 inactivation events unclear"]},{"year":2012,"claim":"Identified an additional enzymatic dimension by showing all EPI64-family members possess RasGAP activity in cells.","evidence":"FRET Ras sensors, Bos pull-down for active Ras, and time-lapse FRET in COS-7 cells","pmids":["23248241"],"confidence":"Medium","gaps":["No in vitro reconstitution with purified proteins","Physiological context of RasGAP activity not defined"]},{"year":2015,"claim":"Placed EPI64 in a lipid-signaling-regulated endocytic pathway in β-cells, downstream of PIP3-recruited ARNO.","evidence":"Co-IP of EPI64 with ARNO, PI3K inhibition, and glucose-stimulated endocytosis assays in β-cells","pmids":["26683831"],"confidence":"Medium","gaps":["Single-lab co-IP without reciprocal structural mapping","Which Rab/Arf substrate executes the endocytic step unclear"]},{"year":2017,"claim":"Established Rab35 as a substrate and tied EPI64 to vascular secretion and selective autophagy regulation.","evidence":"RabGAP screen for WPB exocytosis, reciprocal co-IP, GAP-dead and Rab35(Q67A) rescue, knockdown; NDP52 recruitment and mitophagy assays","pmids":["28566286","28848034"],"confidence":"High","gaps":["Direct in vitro Rab35-GAP kinetics not reported","How EPI64 selects Rab35 versus Rab27/Rab8a substrates in vivo unresolved"]},{"year":2019,"claim":"Extended Rab35 regulation to the cilium, linking EPI64 to ciliary length control and ciliary Rab35 localization.","evidence":"siRNA knockdown, GFP-TBC1D10A ciliary live imaging, and cilium length measurements","pmids":["31432619"],"confidence":"Medium","gaps":["Mechanism coupling Rab35 inactivation to length control unclear","Single-lab localization data"]},{"year":2019,"claim":"Proposed additional substrate (RAB13) and an upstream β-cell receptor (IRR), broadening but not yet solidifying the regulatory network.","evidence":"Colocalization with RAB13/VEGFR2 and Erk signaling assays; EPI64-interactor identification with IRR knockdown endocytosis assays","pmids":["31527750","31353211"],"confidence":"Low","gaps":["No direct GAP activity assay for RAB13","EPI64–IRR interaction detection method not specified; single-lab, unreplicated"]},{"year":null,"claim":"How EPI64 selects among its multiple Rab substrates (Rab27A, Rab35, Rab8a, RAB13) and integrates concurrent Arf6 and Ras activities at distinct membranes remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model distinguishing substrate engagement","Spatial/temporal logic of competing GAP activities undefined","No loss-of-function organismal phenotype reported in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,4,8]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,5,8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,5]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2,4,6]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,3,5,7]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[6,7]}],"complexes":[],"partners":["EBP50","ARF6","RAB27A","RAB35","RAB8A","JFC1","ARNO"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BXI6","full_name":"TBC1 domain family member 10A","aliases":["EBP50-PDX interactor of 64 kDa","EPI64 protein","Rab27A-GAP-alpha"],"length_aa":508,"mass_kda":57.1,"function":"GTPase-activating protein (GAP) specific for RAB27A and RAB35 (PubMed:16923811, PubMed:30905672). Does not show GAP activity for RAB2A, RAB3A and RAB4A (PubMed:16923811)","subcellular_location":"Cell projection, microvillus","url":"https://www.uniprot.org/uniprotkb/Q9BXI6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TBC1D10A","classification":"Not Classified","n_dependent_lines":18,"n_total_lines":1208,"dependency_fraction":0.014900662251655629},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TBC1D10A","total_profiled":1310},"omim":[{"mim_id":"613620","title":"TBC1 DOMAIN FAMILY, MEMBER 10B; TBC1D10B","url":"https://www.omim.org/entry/613620"},{"mim_id":"610020","title":"TBC1 DOMAIN FAMILY, MEMBER 10A; TBC1D10A","url":"https://www.omim.org/entry/610020"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TBC1D10A"},"hgnc":{"alias_symbol":["EPI64","AC004997.C22.2"],"prev_symbol":["TBC1D10"]},"alphafold":{"accession":"Q9BXI6","domains":[{"cath_id":"1.10.8.270","chopping":"76-100_115-226","consensus_level":"medium","plddt":95.6736,"start":76,"end":226},{"cath_id":"1.10.472.80","chopping":"233-399","consensus_level":"medium","plddt":94.1692,"start":233,"end":399}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXI6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXI6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BXI6-F1-predicted_aligned_error_v6.png","plddt_mean":76.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TBC1D10A","jax_strain_url":"https://www.jax.org/strain/search?query=TBC1D10A"},"sequence":{"accession":"Q9BXI6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BXI6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BXI6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BXI6"}},"corpus_meta":[{"pmid":"17562788","id":"PMC_17562788","title":"Specific Rab GTPase-activating proteins define the Shiga toxin and epidermal growth factor uptake pathways.","date":"2007","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17562788","citation_count":126,"is_preprint":false},{"pmid":"16923811","id":"PMC_16923811","title":"Identification of EPI64 as a GTPase-activating protein specific for Rab27A.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16923811","citation_count":75,"is_preprint":false},{"pmid":"28848034","id":"PMC_28848034","title":"Rab35 GTPase recruits NDP52 to autophagy targets.","date":"2017","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/28848034","citation_count":75,"is_preprint":false},{"pmid":"17145964","id":"PMC_17145964","title":"EPI64 regulates microvillar subdomains and structure.","date":"2006","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17145964","citation_count":72,"is_preprint":false},{"pmid":"11285285","id":"PMC_11285285","title":"Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11285285","citation_count":66,"is_preprint":false},{"pmid":"31432619","id":"PMC_31432619","title":"Rab35 controls cilium length, function and membrane composition.","date":"2019","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31432619","citation_count":38,"is_preprint":false},{"pmid":"28566286","id":"PMC_28566286","title":"Rab35 protein regulates evoked exocytosis of endothelial Weibel-Palade bodies.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28566286","citation_count":31,"is_preprint":false},{"pmid":"31527750","id":"PMC_31527750","title":"Regulation of VEGFR2 trafficking and signaling by Rab GTPase-activating proteins.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31527750","citation_count":28,"is_preprint":false},{"pmid":"30763678","id":"PMC_30763678","title":"Ubiquitylome profiling of Parkin-null brain reveals dysregulation of calcium homeostasis factors ATP1A2, Hippocalcin and GNA11, reflected by altered firing of noradrenergic neurons.","date":"2019","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/30763678","citation_count":27,"is_preprint":false},{"pmid":"22219378","id":"PMC_22219378","title":"EPI64 interacts with Slp1/JFC1 to coordinate Rab8a and Arf6 membrane trafficking.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22219378","citation_count":24,"is_preprint":false},{"pmid":"26683831","id":"PMC_26683831","title":"PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a.","date":"2015","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26683831","citation_count":22,"is_preprint":false},{"pmid":"30060175","id":"PMC_30060175","title":"Whole exome sequencing analysis in severe chronic obstructive pulmonary disease.","date":"2018","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30060175","citation_count":22,"is_preprint":false},{"pmid":"21832089","id":"PMC_21832089","title":"EPI64 protein functions as a physiological GTPase-activating protein for Rab27 protein and regulates amylase release in rat parotid acinar cells.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21832089","citation_count":15,"is_preprint":false},{"pmid":"23671284","id":"PMC_23671284","title":"EPI64B acts as a GTPase-activating protein for Rab27B in pancreatic acinar cells.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23671284","citation_count":15,"is_preprint":false},{"pmid":"25776502","id":"PMC_25776502","title":"Quercetin derivatives regulate melanosome transportation via EPI64 inhibition and elongate the cell shape of B16 melanoma cells.","date":"2015","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/25776502","citation_count":10,"is_preprint":false},{"pmid":"23248241","id":"PMC_23248241","title":"All members of the EPI64 subfamily of TBC/RabGAPs also have GAP activities towards Ras.","date":"2012","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23248241","citation_count":9,"is_preprint":false},{"pmid":"30071094","id":"PMC_30071094","title":"RNA variant identification discrepancy among splice-aware alignment algorithms.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30071094","citation_count":9,"is_preprint":false},{"pmid":"34843939","id":"PMC_34843939","title":"Embryonic expression patterns of TBC1D10 subfamily genes in zebrafish.","date":"2021","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/34843939","citation_count":2,"is_preprint":false},{"pmid":"31353211","id":"PMC_31353211","title":"IRR is involved in glucose-induced endocytosis after insulin secretion.","date":"2019","source":"Journal of pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31353211","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11340,"output_tokens":3522,"usd":0.043425,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10946,"output_tokens":3373,"usd":0.069528,"stage2_stop_reason":"end_turn"},"total_usd":0.112953,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"EPI64 (TBC1D10A) was identified as a TBC/RabGAP domain-containing microvillar protein that binds preferentially to the first PDZ domain of EBP50 and E3KARP via its C-terminal DTYL motif; mutation to DTYLA abolishes PDZ binding and microvillar localization.\",\n      \"method\": \"Affinity chromatography from placental microvilli, PDZ domain binding assays, site-directed mutagenesis, colocalization by immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (affinity chromatography, mutagenesis, colocalization), replicated in subsequent studies\",\n      \"pmids\": [\"11285285\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"EPI64 (TBC1D10A) is a specific GTPase-activating protein (GAP) for Rab27A; it induces melanosome aggregation in melanocytes, traps GTP-Rab27A via the Slac2-a SHD effector domain in cells, and mutations in the catalytic TBC domain abolish GAP activity and melanosome aggregation.\",\n      \"method\": \"Functional screen of 40 TBC proteins in melanocytes (melanosome aggregation assay), GTP-Rab27A trapping assay, in vitro Rab27A-GAP activity assay, catalytic domain mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro GAP assay plus mutagenesis plus cell-based functional assay; replicated in subsequent independent studies\",\n      \"pmids\": [\"16923811\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"EPI64 (TBC1D10A) regulates microvillar structure: overexpression relocalizes EPI64 and EBP50 to the microvillar base; uncoupling EPI64 from EBP50, mislocalizing its TBC domain, or knockdown of EBP50 all result in loss of microvilli. The TBC domain of EPI64 binds directly to Arf6-GTP and overexpression of the TBC domain increases Arf6-GTP levels; expression of dominant-active Arf6 causes microvillar loss.\",\n      \"method\": \"High-resolution light microscopy, overexpression and dominant-negative constructs, siRNA knockdown, direct binding assay (TBC domain vs. Arf6-GTP), GTP-bound Arf6 measurements\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (imaging, binding assay, KD, OE with mutagenesis) in a single focused study\",\n      \"pmids\": [\"17145964\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"TBC1D10A–C were identified in a screen of 39 human RabGAPs as specific regulators of Shiga toxin trafficking from the cell surface to the Golgi apparatus, without affecting EGF uptake.\",\n      \"method\": \"Genome-wide RabGAP overexpression screen; Shiga toxin and EGF trafficking assays in HeLa cells\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — screen-based identification with defined readout, but mechanistic details for TBC1D10A specifically are limited to this screen result\",\n      \"pmids\": [\"17562788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"EPI64 (TBC1D10A) acts as a physiological Rab27-GAP in rat parotid acinar cells: it localizes to the apical plasma membrane, an anti-TBC domain antibody blocks reduction of GTP-Rab27 in permeabilized cells and inhibits amylase release dose-dependently, and EPI64 expression increases upon isoproterenol stimulation to enhance amylase secretion.\",\n      \"method\": \"Subcellular fractionation, immunohistochemistry, streptolysin-O permeabilization with anti-EPI64 antibody inhibition, antisense oligonucleotide knockdown, amylase release assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal approaches (antibody inhibition, antisense KD, fractionation) in a physiologically relevant cell type, consistent with prior in vitro GAP data\",\n      \"pmids\": [\"21832089\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"EPI64 (TBC1D10A) regulates Arf6-dependent membrane trafficking: expression induces actin-coated vacuoles (an Arf6-activation phenotype) dependent on its RabGAP activity; EPI64 lowers Rab8a-GTP levels and directly binds the Rab8a effector JFC1 via its C-terminal region to recruit Rab8a-GTP for deactivation, coordinating Arf6 and Rab8a membrane trafficking.\",\n      \"method\": \"Overexpression of wild-type and GAP-dead mutants, Rab8-GTP pull-down, direct binding assay (EPI64 C-terminus vs. JFC1), co-localization, mutant rescue experiments\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding assay, Rab8-GTP pull-down, and multiple mutant analyses providing mechanistic model in single focused study\",\n      \"pmids\": [\"22219378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"All three EPI64 subfamily members (EPI64A/TBC1D10A, EPI64B/TBC1D10B, EPI64C/TBC1D10C) possess RasGAP activity in vivo, as shown by FRET-based Ras activity sensors, Bos pull-down assay, and time-lapse FRET imaging. EPI64A and EPI64B localize predominantly to the cell periphery (plasma membrane).\",\n      \"method\": \"Spectrofluorometry with FRET sensors, Bos pull-down assay for active Ras, time-lapse confocal FRET imaging in COS-7 cells\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — three independent in-cell methods from a single lab; no in vitro reconstitution with purified proteins\",\n      \"pmids\": [\"23248241\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In pancreatic β-cells, EPI64 (TBC1D10A) interacts with the Arf6-GEF ARNO (CYTH2); glucose-induced PI3K activation generates PIP3 that recruits ARNO to the plasma membrane, which in turn recruits EPI64 to regulate the early stage of endocytosis following insulin secretion.\",\n      \"method\": \"Co-immunoprecipitation (EPI64 with ARNO), PI3K inhibition, glucose stimulation assays, endocytosis assays in pancreatic β-cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-IP identifies binding partner, multiple cell-based functional assays; single lab study\",\n      \"pmids\": [\"26683831\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TBC1D10A acts as a GAP for Rab35 in human endothelial cells: TBC1D10A overexpression inhibits histamine-evoked Weibel-Palade body exocytosis in a GAP-activity-dependent manner, Rab35 co-immunoprecipitates with TBC1D10A, and expression of the GAP-insensitive Rab35(Q67A) mutant rescues the inhibitory effect of TBC1D10A.\",\n      \"method\": \"Genome-wide RabGAP overexpression screen for WPB exocytosis, co-immunoprecipitation, GAP-dead mutant rescue, Rab35 dominant-negative and siRNA knockdown, von Willebrand factor and P-selectin secretion assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP, GAP-dead mutagenesis, dominant-negative and knockdown rescue all converge on the same conclusion in one study\",\n      \"pmids\": [\"28566286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TBC1D10A (as a Rab35-GAP) inhibits Rab35-mediated recruitment of the autophagy receptor NDP52 to bacteria-containing endosomes and to damaged mitochondria, thereby negatively regulating xenophagy and mitophagy.\",\n      \"method\": \"Overexpression of TBC1D10A GAP, NDP52 recruitment assay to intracellular bacteria and damaged mitochondria, mitophagy and autophagosome maturation assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function and overexpression with defined autophagy readouts; single lab study\",\n      \"pmids\": [\"28848034\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TBC1D10A acts on RAB13 (in addition to Rab27A and Rab35), colocalizes with RAB13 and VEGFR2 in activated endothelial cells, and leads to increased Erk1/2 signaling, opposite to the effect of the paralog TBC1D10B on VEGFR2 signaling.\",\n      \"method\": \"RabGAP overexpression panel, colocalization imaging (TBC1D10A, RAB13, VEGFR2), Erk1/2 and p38 signaling assays, tube formation assay\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — colocalization-based RAB13 substrate inference from a single lab; no direct GAP activity assay for RAB13 reported in abstract\",\n      \"pmids\": [\"31527750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TBC1D10A (GAP for Rab35) and the Rab35-GEF DENND1B both localize to cilia, and TBC1D10A regulates ciliary length and the ciliary localization of Rab35 in mammalian cells.\",\n      \"method\": \"siRNA knockdown, GFP-TBC1D10A live imaging/localization to cilia, cilium length measurements\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment tied to functional consequence (ciliary length), supported by KD phenotype; single lab\",\n      \"pmids\": [\"31432619\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"IRR (insulin receptor-related receptor) was identified as an EPI64-interacting protein in pancreatic β-cells; knockdown of IRR inhibits glucose-induced endocytosis (transferrin uptake), ARNO membrane translocation, and PIP3 generation, placing IRR upstream of PI3K/PIP3 in the EPI64-regulated endocytosis pathway.\",\n      \"method\": \"Protein interaction identification (EPI64-interactor screen), siRNA knockdown of IRR, transferrin uptake assay, ARNO translocation assay, PIP3 measurement\",\n      \"journal\": \"Journal of pharmacological sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single identification method; abstract does not specify how EPI64–IRR interaction was detected\",\n      \"pmids\": [\"31353211\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TBC1D10A (EPI64) is a TBC-domain-containing RabGAP that localizes to apical microvilli via its C-terminal DTYL motif binding to the PDZ domains of the scaffolding protein EBP50, where it stabilizes Arf6-GTP (by binding Arf6-GTP through its TBC domain), inactivates Rab27A/Rab27B (promoting secretory granule exocytosis), inactivates Rab35 (suppressing NDP52-mediated autophagy and regulating ciliary length and Weibel-Palade body exocytosis), inactivates Rab8a (by recruiting it via the Rab8a effector JFC1), and also possesses RasGAP activity; together these activities coordinate microvillar structure, membrane trafficking, secretion, and autophagy.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TBC1D10A (EPI64) is a TBC-domain RabGAP that couples microvillar architecture to membrane trafficking and regulated secretion at the apical plasma membrane [#0, #2]. It is targeted to microvilli through its C-terminal DTYL motif, which binds the first PDZ domain of the scaffold EBP50; uncoupling EPI64 from EBP50 or mislocalizing its TBC domain abolishes both its localization and the integrity of microvilli [#0, #2]. Through its catalytic TBC domain it functions as a GAP for multiple Rab GTPases—Rab27A, where it drives melanosome aggregation and, in parotid acinar cells, controls Rab27-dependent amylase exocytosis [#1, #4]; Rab35, where it suppresses histamine-evoked Weibel-Palade body exocytosis and negatively regulates NDP52-dependent xenophagy and mitophagy while controlling ciliary length and ciliary Rab35 localization [#8, #9, #11]; and Rab8a, which it recruits for inactivation via the effector JFC1 [#5]. In parallel its TBC domain binds and stabilizes Arf6-GTP, linking its GAP activity to Arf6-dependent actin-coated vacuole formation and microvillar remodeling [#2, #5]. In pancreatic β-cells EPI64 is recruited downstream of PI3K/PIP3 by the Arf6-GEF ARNO to regulate endocytosis following insulin secretion [#7]. Beyond these Rab/Arf activities, EPI64 also exhibits RasGAP activity [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established how an uncharacterized microvillar TBC protein is targeted to its site of action, defining the scaffold interaction that anchors EPI64 to microvilli.\",\n      \"evidence\": \"Affinity chromatography from placental microvilli with PDZ binding assays and DTYL-motif mutagenesis\",\n      \"pmids\": [\"11285285\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define a catalytic substrate or GAP target\", \"Functional consequence of microvillar localization unresolved at this stage\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Resolved the catalytic identity of EPI64 by showing its TBC domain is a specific Rab27A-GAP, linking it to organelle (melanosome) transport.\",\n      \"evidence\": \"TBC-protein functional screen in melanocytes, GTP-Rab27A trapping, in vitro Rab27A-GAP assay, and catalytic-domain mutagenesis\",\n      \"pmids\": [\"16923811\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological relevance in secretory tissues not yet shown\", \"Other potential Rab substrates not surveyed\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Connected EPI64's GAP scaffold to microvillar structure and revealed a second small-GTPase activity, showing its TBC domain binds and elevates Arf6-GTP.\",\n      \"evidence\": \"High-resolution imaging, EBP50 knockdown, dominant constructs, and direct TBC-domain–Arf6-GTP binding/GTP-level assays\",\n      \"pmids\": [\"17145964\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which Arf6-GTP binding is reconciled with GAP catalysis unclear\", \"Whether Arf6 binding requires Rab inactivation not resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated that EPI64's Rab27-GAP activity is physiologically required for regulated exocytosis in a native secretory cell.\",\n      \"evidence\": \"Fractionation, anti-TBC antibody inhibition in permeabilized parotid acinar cells, antisense knockdown, and amylase release assays\",\n      \"pmids\": [\"21832089\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream signals controlling EPI64 expression beyond isoproterenol not defined\", \"Direct in vivo Rab27 GTP measurement in this tissue limited\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Expanded the trafficking model by showing EPI64 inactivates Rab8a through effector-mediated recruitment, coordinating Arf6 and Rab8a pathways.\",\n      \"evidence\": \"GAP-dead overexpression, Rab8-GTP pull-down, and direct binding of the EPI64 C-terminus to JFC1\",\n      \"pmids\": [\"22219378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Rab8a recruitment via JFC1 occurs in physiological cell types untested\", \"Relationship to Rab27 inactivation events unclear\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identified an additional enzymatic dimension by showing all EPI64-family members possess RasGAP activity in cells.\",\n      \"evidence\": \"FRET Ras sensors, Bos pull-down for active Ras, and time-lapse FRET in COS-7 cells\",\n      \"pmids\": [\"23248241\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No in vitro reconstitution with purified proteins\", \"Physiological context of RasGAP activity not defined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Placed EPI64 in a lipid-signaling-regulated endocytic pathway in β-cells, downstream of PIP3-recruited ARNO.\",\n      \"evidence\": \"Co-IP of EPI64 with ARNO, PI3K inhibition, and glucose-stimulated endocytosis assays in β-cells\",\n      \"pmids\": [\"26683831\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single-lab co-IP without reciprocal structural mapping\", \"Which Rab/Arf substrate executes the endocytic step unclear\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Established Rab35 as a substrate and tied EPI64 to vascular secretion and selective autophagy regulation.\",\n      \"evidence\": \"RabGAP screen for WPB exocytosis, reciprocal co-IP, GAP-dead and Rab35(Q67A) rescue, knockdown; NDP52 recruitment and mitophagy assays\",\n      \"pmids\": [\"28566286\", \"28848034\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct in vitro Rab35-GAP kinetics not reported\", \"How EPI64 selects Rab35 versus Rab27/Rab8a substrates in vivo unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended Rab35 regulation to the cilium, linking EPI64 to ciliary length control and ciliary Rab35 localization.\",\n      \"evidence\": \"siRNA knockdown, GFP-TBC1D10A ciliary live imaging, and cilium length measurements\",\n      \"pmids\": [\"31432619\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism coupling Rab35 inactivation to length control unclear\", \"Single-lab localization data\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Proposed additional substrate (RAB13) and an upstream β-cell receptor (IRR), broadening but not yet solidifying the regulatory network.\",\n      \"evidence\": \"Colocalization with RAB13/VEGFR2 and Erk signaling assays; EPI64-interactor identification with IRR knockdown endocytosis assays\",\n      \"pmids\": [\"31527750\", \"31353211\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct GAP activity assay for RAB13\", \"EPI64–IRR interaction detection method not specified; single-lab, unreplicated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How EPI64 selects among its multiple Rab substrates (Rab27A, Rab35, Rab8a, RAB13) and integrates concurrent Arf6 and Ras activities at distinct membranes remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model distinguishing substrate engagement\", \"Spatial/temporal logic of competing GAP activities undefined\", \"No loss-of-function organismal phenotype reported in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 4, 8]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 5, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 4, 6]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 3, 5, 7]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EBP50\", \"Arf6\", \"Rab27A\", \"Rab35\", \"Rab8a\", \"JFC1\", \"ARNO\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}