{"gene":"RAB43","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2007,"finding":"RN-tre (USP6NL) is the GAP for RAB43 and controls retrograde transport into the Golgi from the endocytic pathway; expression of RN-tre disrupts Golgi organization and protein transport, establishing RAB43 as a key Rab required for maintenance of functional Golgi structure.","method":"Overexpression of 38 human Rab GAPs with Golgi morphology and protein transport readouts; identification of RN-tre as RAB43-specific GAP","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic functional screen across all human Rab GAPs with multiple orthogonal readouts (Golgi morphology, cargo transport), replicated in subsequent studies","pmids":["17684057"],"is_preprint":false},{"year":2008,"finding":"Dominant-negative RAB43-T32N redistributes Golgi elements to ER exit sites without blocking ER-to-cell-surface trafficking of VSVG-GFP; wild-type RAB43 overexpression redistributes the p150(Glued) subunit of dynactin, indicating a specific role for RAB43 in regulating association of pre-Golgi intermediates with microtubules.","method":"Dominant-negative and overexpression of GFP-RAB43 constructs with live-cell imaging and VSVG-GFP trafficking assays; co-localization of dynactin subunit p150(Glued)","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — dominant-negative and overexpression phenotypes with multiple readouts (Golgi morphology, cargo trafficking, dynactin redistribution) but single lab","pmids":["18664496"],"is_preprint":false},{"year":2011,"finding":"RAB43 depletion causes fragmentation and dispersal of the trans-Golgi network and associated membranes, rendering these compartments unable to support secondary envelopment of HSV-1; RAB43's role in maintaining TGN integrity is required for viral glycoprotein incorporation.","method":"Overexpression of 37 Rab GAPs with infectious titer assays; siRNA knockdown of RAB43 with electron microscopy and virion assembly analysis","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — GAP screen plus siRNA KD with defined ultrastructural and functional phenotypes, single lab","pmids":["21680502"],"is_preprint":false},{"year":2016,"finding":"RAB43 localizes to the Golgi apparatus and LAMP1-negative cytoplasmic vesicles in CD8α+ dendritic cells; RAB43 knockout mice show a specific defect in cross-presentation of cell-associated antigens by CD8α+ and CD103+ DCs but not monocyte-derived DCs, with normal cDC development.","method":"Germline and conditional Rab43 knockout mice; monoclonal antibody localization; in vivo and in vitro cross-presentation assays with cell-associated antigen","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout (germline and conditional) with specific antigen presentation phenotype, specific antibody localization, and cell-type selectivity controls","pmids":["27899443"],"is_preprint":false},{"year":2016,"finding":"RAB43 regulates sorting of a subset of membrane cargo (G(AE) but not VSV-G) through the medial Golgi; overexpressed GFP-RAB43 arrests anterograde transport of G(AE) in a RAB43-positive medial Golgi compartment and inhibits its glycosylation and surface delivery, while siRNA knockdown of RAB43 increases G(AE) surface accumulation.","method":"GFP-RAB43 overexpression and siRNA knockdown with fluorescent cargo trafficking assays, glycosylation assays (endoH resistance), and flow cytometry surface delivery measurements","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complementary overexpression and knockdown approaches with multiple orthogonal readouts (trafficking, glycosylation, surface levels), single lab","pmids":["27053659"],"is_preprint":false},{"year":2017,"finding":"RAB43 specifically regulates anterograde ER-to-Golgi transport of nascent GPCRs (but not non-GPCR membrane proteins); RAB43 directly interacts with GPCRs in an activation-dependent fashion, and the RAB43-binding domain in receptors can confer RAB43-dependent transport on non-GPCR membrane proteins.","method":"Rab GTPase siRNA screen for GPCR surface transport; dominant-negative and constitutively-active RAB43 mutants; co-immunoprecipitation of RAB43 with multiple GPCRs; domain-swap experiments with chimeric proteins","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — systematic Rab screen, direct binding by Co-IP, domain-swap rescue, multiple GPCRs tested, activation-state dependence established","pmids":["29069590"],"is_preprint":false},{"year":2021,"finding":"RAB43 differentially regulates surface expression and signaling of endogenous α2-adrenergic receptor and muscarinic acetylcholine receptor in primary neurons, and exerts distinct effects on dendritic and postsynaptic transport of specific receptor subtypes (α2B-AR and M3 mAChR) via direct interaction; this neuron-specific sorting activity is dictated by direct RAB43-receptor interaction.","method":"Dominant-negative inhibition and CRISPR-Cas9 KO of Rab43 in primary neurons; co-immunoprecipitation; dendritic and postsynaptic localization imaging; signaling assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO plus dominant-negative, direct interaction by Co-IP, multiple receptor subtypes, neuronal and non-neuronal cell comparison","pmids":["33676895"],"is_preprint":false},{"year":2022,"finding":"RAB43 directly interacts with CD91 (LRP1) to mediate its anterograde transport from the cytoplasm to the cell surface in macrophages; HMGB1 suppresses RAB43 expression, thereby impairing CD91 surface transport and macrophage-mediated efferocytosis.","method":"Co-immunoprecipitation of RAB43 with CD91; Rab43 knockdown and overexpression with CD91 surface localization assays; Rab43 KO mice with ALI model","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP for direct interaction, KD/KO with defined cargo transport phenotype, in vivo validation, single lab","pmids":["35392093"],"is_preprint":false},{"year":2025,"finding":"Crystal structure of the RN-Tre (USP6NL)–RAB43 complex reveals a bipartite recognition mechanism: the RN-Tre N-terminal subdomain catalytically remodels RAB43 Switch regions while the C-terminal subdomain engages Switch II and reorients the hydrophobic triad to confer substrate specificity; Leu146 and C-terminal residues of RN-Tre are key specificity determinants; disease-associated RN-Tre mutations impair GAP activity leading to aberrant Golgi architecture and endocytic trafficking.","method":"X-ray crystallography of RN-Tre–RAB43 complex; mutational analysis of specificity determinants; GAP activity assays; Golgi morphology assays with disease-associated mutants","journal":"International journal of biological macromolecules","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutational validation plus in vitro GAP activity assays plus cellular functional readouts in one study","pmids":["41401861"],"is_preprint":false},{"year":2025,"finding":"LRRK1 phosphorylates RAB43 at the Switch-II region; this represents a novel kinase:Rab pair identified by in vitro kinase profiling.","method":"In vitro kinase profiling of LRRK1, LRRK2, DYRK1A, MST1, and TBK1 against a panel of Rab GTPases","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assay, preprint, no cellular validation for LRRK1:Rab43 pair specifically","pmids":["bio_10.1101_2025.04.09.647999"],"is_preprint":true},{"year":2026,"finding":"RAB43 promotes ubiquitination and degradation of MyD88 in macrophages; Rab43 KO elevates MyD88 protein levels (by ~80%) without affecting MyD88 mRNA, leading to overactivation of the MAPK-NF-κB pathway; Co-IP confirms RAB43 regulates the interaction of MyD88 with ubiquitin protein, and Rab43 deficiency reduces MyD88-ubiquitin levels by 58% accompanied by downregulation of ubiquitinase genes A20, SPOP, HOIL-1, and OTUD4.","method":"Myeloid-specific Rab43 KO mice; LPS-induced ALI model; co-immunoprecipitation; Western blot; qPCR; flow cytometry","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO mouse model, Co-IP for ubiquitin interaction, multiple biochemical readouts, single lab","pmids":["41501355"],"is_preprint":false}],"current_model":"RAB43 is a Rab GTPase that localizes to the Golgi apparatus and functions in anterograde ER-to-Golgi trafficking of specific cargo (especially GPCRs and select membrane proteins via direct interaction), retrograde endosome-to-Golgi transport, and maintenance of Golgi structure; it is inactivated by the GAP RN-tre (USP6NL) through a structurally defined bipartite mechanism, can be phosphorylated at its Switch-II region by LRRK1, mediates postsynaptic GPCR targeting in neurons, supports cross-presentation by CD8α+ dendritic cells, controls anterograde transport of CD91 in macrophages to enable efferocytosis, and promotes MyD88 ubiquitination and degradation to restrain TLR4-MyD88-MAPK-NF-κB inflammatory signaling."},"narrative":{"mechanistic_narrative":"RAB43 is a Golgi-localized Rab GTPase that organizes pre-Golgi and trans-Golgi membrane compartments and selectively sorts specific cargo through the secretory pathway [PMID:17684057, PMID:27899443, PMID:27053659]. It maintains functional Golgi architecture: its depletion fragments and disperses the trans-Golgi network, and the GTPase-activating protein RN-tre (USP6NL) inactivates RAB43 and controls retrograde endosome-to-Golgi transport [PMID:17684057, PMID:21680502]. A crystal structure of the RN-tre–RAB43 complex defines a bipartite recognition mechanism in which the GAP N-terminal subdomain catalytically remodels the RAB43 Switch regions while the C-terminal subdomain engages Switch II to confer substrate specificity, and disease-associated RN-tre mutations that impair this GAP activity produce aberrant Golgi architecture [PMID:41401861]. Functionally, RAB43 acts as a cargo-selective trafficking factor: it routes a subset of membrane proteins through the medial Golgi [PMID:27053659] and drives anterograde ER-to-Golgi transport of nascent GPCRs through direct, activation-dependent receptor binding, a binding domain sufficient to confer RAB43-dependent transport on non-GPCR proteins [PMID:29069590]. This sorting activity extends to specialized cell types: RAB43 governs dendritic and postsynaptic targeting of α2-adrenergic and muscarinic receptors in neurons via direct interaction [PMID:33676895], is required for cross-presentation of cell-associated antigens by CD8α+ dendritic cells [PMID:27899443], mediates anterograde surface transport of CD91 (LRP1) to support macrophage efferocytosis [PMID:35392093], and restrains TLR4–MyD88–MAPK–NF-κB inflammatory signaling by promoting ubiquitination and degradation of MyD88 in macrophages [PMID:41501355].","teleology":[{"year":2007,"claim":"Identifying the GAP for RAB43 established that the protein is a bona fide cycling Rab and placed it as a regulator of retrograde traffic into the Golgi and of Golgi integrity.","evidence":"Overexpression screen of 38 human Rab GAPs with Golgi morphology and protein transport readouts, identifying RN-tre (USP6NL) as the RAB43-specific GAP","pmids":["17684057"],"confidence":"High","gaps":["Did not define the cargo RAB43 transports","Did not identify effectors downstream of active RAB43"]},{"year":2008,"claim":"Dominant-negative and overexpression phenotypes localized RAB43 function to the pre-Golgi/ER-exit-site interface and linked it to microtubule-based positioning of Golgi intermediates.","evidence":"GFP-RAB43 dominant-negative (T32N) and overexpression with live-cell imaging, VSVG-GFP trafficking, and dynactin p150(Glued) co-localization","pmids":["18664496"],"confidence":"Medium","gaps":["Mechanism connecting RAB43 to dynactin not resolved","Single lab; no direct effector identified"]},{"year":2011,"claim":"Showed that RAB43-dependent TGN integrity is functionally required, using HSV-1 secondary envelopment as a sensitive readout of intact trans-Golgi membranes.","evidence":"Rab GAP overexpression screen plus RAB43 siRNA with electron microscopy and virion assembly/titer assays","pmids":["21680502"],"confidence":"Medium","gaps":["Did not establish whether the defect reflects loss of a direct RAB43 cargo or general Golgi disruption"]},{"year":2016,"claim":"Two studies converged on RAB43 as a cargo-selective sorter — through the medial Golgi for a subset of membrane proteins and as a requirement for dendritic-cell cross-presentation — moving beyond a purely structural role.","evidence":"GFP-RAB43 overexpression/siRNA with glycosylation and surface-delivery cargo assays; germline and conditional Rab43 knockout mice with cross-presentation assays and antibody localization","pmids":["27053659","27899443"],"confidence":"High","gaps":["Molecular basis of cargo selectivity not yet defined","Identity of the cross-presentation cargo/compartment not pinned down"]},{"year":2017,"claim":"Demonstrated direct, activation-dependent RAB43–GPCR binding and that the receptor RAB43-binding domain is transferable, explaining how RAB43 achieves cargo specificity in anterograde ER-to-Golgi transport.","evidence":"Rab siRNA screen for GPCR surface transport, dominant-negative/constitutively-active mutants, Co-IP with multiple GPCRs, and domain-swap chimeras","pmids":["29069590"],"confidence":"High","gaps":["Structural basis of RAB43–receptor recognition not determined","Effector machinery linking bound cargo to vesicle movement unknown"]},{"year":2021,"claim":"Extended the direct-interaction sorting model to neurons, showing RAB43 controls subtype-specific dendritic and postsynaptic receptor targeting and signaling.","evidence":"Dominant-negative and CRISPR-Cas9 Rab43 KO in primary neurons with Co-IP, postsynaptic imaging, and signaling assays for α2B-AR and M3 mAChR","pmids":["33676895"],"confidence":"High","gaps":["How RAB43 distinguishes dendritic vs somatic routing not resolved"]},{"year":2022,"claim":"Identified CD91/LRP1 as a RAB43 cargo in macrophages and connected RAB43 expression control to efferocytosis, linking the trafficking activity to a tissue function.","evidence":"Co-IP of RAB43 with CD91, knockdown/overexpression surface-localization assays, and Rab43 KO mice in an acute lung injury model","pmids":["35392093"],"confidence":"Medium","gaps":["Mechanism by which HMGB1 suppresses RAB43 expression not detailed","Single lab"]},{"year":2025,"claim":"A crystal structure of the RN-tre–RAB43 complex resolved the bipartite mechanism of GAP specificity and tied disease-associated RN-tre mutations to defective RAB43 inactivation and Golgi/endocytic phenotypes.","evidence":"X-ray crystallography of the RN-tre–RAB43 complex with mutational analysis, in vitro GAP assays, and Golgi morphology assays of disease mutants","pmids":["41401861"],"confidence":"High","gaps":["No structure of active RAB43 bound to an effector or cargo","GEF for RAB43 not identified"]},{"year":2025,"claim":"An in vitro kinase screen nominated LRRK1 as a kinase phosphorylating RAB43 at Switch II, raising the possibility of kinase-regulated RAB43 cycling.","evidence":"In vitro kinase profiling of LRRK1, LRRK2, DYRK1A, MST1, and TBK1 against a Rab GTPase panel (preprint)","pmids":["bio_10.1101_2025.04.09.647999"],"confidence":"Low","gaps":["No cellular validation of LRRK1:RAB43 phosphorylation","Functional consequence of Switch-II phosphorylation unknown","Preprint, not peer-reviewed"]},{"year":2026,"claim":"Revealed a signaling-regulatory role: RAB43 promotes MyD88 ubiquitination and degradation to dampen TLR4–MyD88–MAPK–NF-κB inflammatory output in macrophages.","evidence":"Myeloid-specific Rab43 KO mice in an LPS-induced ALI model with Co-IP of MyD88–ubiquitin, Western blot, qPCR of deubiquitinase genes, and flow cytometry","pmids":["41501355"],"confidence":"Medium","gaps":["Whether RAB43 acts directly on MyD88 ubiquitination or via its trafficking activity is unresolved","Mechanism linking RAB43 to ubiquitinase gene expression (A20, SPOP, HOIL-1, OTUD4) unknown"]},{"year":null,"claim":"The activating GEF, the downstream effectors that link cargo-bound RAB43 to vesicle budding/movement, and whether Switch-II phosphorylation regulates RAB43 cycling in cells remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No GEF identified for RAB43","No effector bridging RAB43 to motor/coat machinery characterized","Cellular role of LRRK1-mediated phosphorylation not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[0,8]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[5,6,7]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,2,3,4]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,4,5]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[5,6,7]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[3,7,10]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,2]}],"complexes":[],"partners":["USP6NL","CD91","MYD88","LRRK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86YS6","full_name":"Ras-related protein Rab-43","aliases":["Ras-related protein Rab-41"],"length_aa":212,"mass_kda":23.3,"function":"The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:16086013, PubMed:17562788, PubMed:17684057, PubMed:18664496, PubMed:21255211, PubMed:29069590). Involved in retrograde transport from the endocytic pathway to the Golgi apparatus (PubMed:17684057). Required for the structural integrity of the Golgi complex (PubMed:17684057, PubMed:18664496). Also controls the anterograde ER-to-Golgi transport of nascent G-protein-coupled receptors (including ADRA2A, ADRA2B, ADRA2C, ADRA1B, ADRB2 and AGTR1) and regulates the ER sorting of GPCR members by virtue of its ability to interact directly (PubMed:18664496, PubMed:29069590). Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network (PubMed:17562788). Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis (PubMed:21255211)","subcellular_location":"Golgi apparatus; Golgi apparatus, cis-Golgi network membrane; Golgi apparatus, trans-Golgi network membrane; Endoplasmic reticulum membrane; Endoplasmic reticulum-Golgi intermediate compartment membrane; Cytoplasmic vesicle, phagosome membrane","url":"https://www.uniprot.org/uniprotkb/Q86YS6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RAB43","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":true,"resolved_as":"RAB11B","ensg_id":"ENSG00000185236","cell_line_id":"CID000417","localizations":[{"compartment":"golgi","grade":3},{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"RAB11A","stoichiometry":10.0},{"gene":"SCAMP2","stoichiometry":10.0},{"gene":"SCAMP4","stoichiometry":4.0},{"gene":"VAMP3","stoichiometry":4.0},{"gene":"ELOVL1","stoichiometry":0.2},{"gene":"GDI1","stoichiometry":0.2},{"gene":"GDI2","stoichiometry":0.2},{"gene":"VAMP3;VAMP2","stoichiometry":0.2},{"gene":"SLC35F2","stoichiometry":0.2},{"gene":"RAB11FIP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000417","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"liver","ntpm":44.2}],"url":"https://www.proteinatlas.org/search/RAB43"},"hgnc":{"alias_symbol":["RAB41","RAB11B","ISY1"],"prev_symbol":[]},"alphafold":{"accession":"Q86YS6","domains":[{"cath_id":"3.40.50.300","chopping":"13-185","consensus_level":"high","plddt":93.6755,"start":13,"end":185}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YS6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YS6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YS6-F1-predicted_aligned_error_v6.png","plddt_mean":84.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RAB43","jax_strain_url":"https://www.jax.org/strain/search?query=RAB43"},"sequence":{"accession":"Q86YS6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86YS6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86YS6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YS6"}},"corpus_meta":[{"pmid":"17684057","id":"PMC_17684057","title":"Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17684057","citation_count":173,"is_preprint":false},{"pmid":"18664496","id":"PMC_18664496","title":"Rab18 and Rab43 have key roles in ER-Golgi trafficking.","date":"2008","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/18664496","citation_count":137,"is_preprint":false},{"pmid":"27899443","id":"PMC_27899443","title":"RAB43 facilitates cross-presentation of cell-associated antigens by CD8α+ dendritic cells.","date":"2016","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/27899443","citation_count":70,"is_preprint":false},{"pmid":"21680502","id":"PMC_21680502","title":"Analysis of Rab GTPase-activating proteins indicates that Rab1a/b and Rab43 are important for herpes simplex virus 1 secondary envelopment.","date":"2011","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/21680502","citation_count":66,"is_preprint":false},{"pmid":"29069590","id":"PMC_29069590","title":"The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29069590","citation_count":48,"is_preprint":false},{"pmid":"35392093","id":"PMC_35392093","title":"Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the Rab43-Controlled Cell Surface Transport of CD91.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35392093","citation_count":25,"is_preprint":false},{"pmid":"33676895","id":"PMC_33676895","title":"Rab43 GTPase directs postsynaptic trafficking and neuron-specific sorting of G protein-coupled receptors.","date":"2021","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/33676895","citation_count":18,"is_preprint":false},{"pmid":"27053659","id":"PMC_27053659","title":"Rab43 regulates the sorting of a subset of membrane protein cargo through the medial Golgi.","date":"2016","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/27053659","citation_count":14,"is_preprint":false},{"pmid":"32102752","id":"PMC_32102752","title":"Downregulation of TNFRSF19 and RAB43 by a novel miRNA, miR-HCC3, promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma cells.","date":"2020","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/32102752","citation_count":12,"is_preprint":false},{"pmid":"32210585","id":"PMC_32210585","title":"RAB43 Promotes Gastric Cancer Cell Proliferation and Metastasis via Regulating the PI3K/AKT Signaling Pathway.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32210585","citation_count":10,"is_preprint":false},{"pmid":"31226964","id":"PMC_31226964","title":"A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome.","date":"2019","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31226964","citation_count":5,"is_preprint":false},{"pmid":"35597125","id":"PMC_35597125","title":"miR-4742-5p promotes invasiveness of gastric cancer via targeting Rab43: An in vitro study.","date":"2022","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/35597125","citation_count":4,"is_preprint":false},{"pmid":"40601689","id":"PMC_40601689","title":"circRNA_BMPR2 affects the progression of polycystic ovary syndrome by regulating the expression of Rab43.","date":"2025","source":"Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/40601689","citation_count":0,"is_preprint":false},{"pmid":"39229605","id":"PMC_39229605","title":"RAB43 Promotes Gastric Cancer Cell Proliferation and Metastasis via Regulating the PI3K/AKT Signaling Pathway [Retraction].","date":"2024","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/39229605","citation_count":0,"is_preprint":false},{"pmid":"41501355","id":"PMC_41501355","title":"Rab43 mitigates the inflammatory response in acute lung injury via MyD88 ubiquitination.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41501355","citation_count":0,"is_preprint":false},{"pmid":"41401861","id":"PMC_41401861","title":"Molecular basis of Rab43 inactivation by RN-Tre in endocytic trafficking unveils a general Rab-GAP recognition mechanism.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/41401861","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.09.647999","title":"Selectivity profiles and substrate recognition of Rab phosphorylating kinases","date":"2025-04-10","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.09.647999","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9999,"output_tokens":3018,"usd":0.037634,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10399,"output_tokens":3712,"usd":0.072398,"stage2_stop_reason":"end_turn"},"total_usd":0.110032,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"RN-tre (USP6NL) is the GAP for RAB43 and controls retrograde transport into the Golgi from the endocytic pathway; expression of RN-tre disrupts Golgi organization and protein transport, establishing RAB43 as a key Rab required for maintenance of functional Golgi structure.\",\n      \"method\": \"Overexpression of 38 human Rab GAPs with Golgi morphology and protein transport readouts; identification of RN-tre as RAB43-specific GAP\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic functional screen across all human Rab GAPs with multiple orthogonal readouts (Golgi morphology, cargo transport), replicated in subsequent studies\",\n      \"pmids\": [\"17684057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Dominant-negative RAB43-T32N redistributes Golgi elements to ER exit sites without blocking ER-to-cell-surface trafficking of VSVG-GFP; wild-type RAB43 overexpression redistributes the p150(Glued) subunit of dynactin, indicating a specific role for RAB43 in regulating association of pre-Golgi intermediates with microtubules.\",\n      \"method\": \"Dominant-negative and overexpression of GFP-RAB43 constructs with live-cell imaging and VSVG-GFP trafficking assays; co-localization of dynactin subunit p150(Glued)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — dominant-negative and overexpression phenotypes with multiple readouts (Golgi morphology, cargo trafficking, dynactin redistribution) but single lab\",\n      \"pmids\": [\"18664496\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"RAB43 depletion causes fragmentation and dispersal of the trans-Golgi network and associated membranes, rendering these compartments unable to support secondary envelopment of HSV-1; RAB43's role in maintaining TGN integrity is required for viral glycoprotein incorporation.\",\n      \"method\": \"Overexpression of 37 Rab GAPs with infectious titer assays; siRNA knockdown of RAB43 with electron microscopy and virion assembly analysis\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — GAP screen plus siRNA KD with defined ultrastructural and functional phenotypes, single lab\",\n      \"pmids\": [\"21680502\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"RAB43 localizes to the Golgi apparatus and LAMP1-negative cytoplasmic vesicles in CD8α+ dendritic cells; RAB43 knockout mice show a specific defect in cross-presentation of cell-associated antigens by CD8α+ and CD103+ DCs but not monocyte-derived DCs, with normal cDC development.\",\n      \"method\": \"Germline and conditional Rab43 knockout mice; monoclonal antibody localization; in vivo and in vitro cross-presentation assays with cell-associated antigen\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout (germline and conditional) with specific antigen presentation phenotype, specific antibody localization, and cell-type selectivity controls\",\n      \"pmids\": [\"27899443\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"RAB43 regulates sorting of a subset of membrane cargo (G(AE) but not VSV-G) through the medial Golgi; overexpressed GFP-RAB43 arrests anterograde transport of G(AE) in a RAB43-positive medial Golgi compartment and inhibits its glycosylation and surface delivery, while siRNA knockdown of RAB43 increases G(AE) surface accumulation.\",\n      \"method\": \"GFP-RAB43 overexpression and siRNA knockdown with fluorescent cargo trafficking assays, glycosylation assays (endoH resistance), and flow cytometry surface delivery measurements\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complementary overexpression and knockdown approaches with multiple orthogonal readouts (trafficking, glycosylation, surface levels), single lab\",\n      \"pmids\": [\"27053659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RAB43 specifically regulates anterograde ER-to-Golgi transport of nascent GPCRs (but not non-GPCR membrane proteins); RAB43 directly interacts with GPCRs in an activation-dependent fashion, and the RAB43-binding domain in receptors can confer RAB43-dependent transport on non-GPCR membrane proteins.\",\n      \"method\": \"Rab GTPase siRNA screen for GPCR surface transport; dominant-negative and constitutively-active RAB43 mutants; co-immunoprecipitation of RAB43 with multiple GPCRs; domain-swap experiments with chimeric proteins\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — systematic Rab screen, direct binding by Co-IP, domain-swap rescue, multiple GPCRs tested, activation-state dependence established\",\n      \"pmids\": [\"29069590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RAB43 differentially regulates surface expression and signaling of endogenous α2-adrenergic receptor and muscarinic acetylcholine receptor in primary neurons, and exerts distinct effects on dendritic and postsynaptic transport of specific receptor subtypes (α2B-AR and M3 mAChR) via direct interaction; this neuron-specific sorting activity is dictated by direct RAB43-receptor interaction.\",\n      \"method\": \"Dominant-negative inhibition and CRISPR-Cas9 KO of Rab43 in primary neurons; co-immunoprecipitation; dendritic and postsynaptic localization imaging; signaling assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO plus dominant-negative, direct interaction by Co-IP, multiple receptor subtypes, neuronal and non-neuronal cell comparison\",\n      \"pmids\": [\"33676895\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RAB43 directly interacts with CD91 (LRP1) to mediate its anterograde transport from the cytoplasm to the cell surface in macrophages; HMGB1 suppresses RAB43 expression, thereby impairing CD91 surface transport and macrophage-mediated efferocytosis.\",\n      \"method\": \"Co-immunoprecipitation of RAB43 with CD91; Rab43 knockdown and overexpression with CD91 surface localization assays; Rab43 KO mice with ALI model\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP for direct interaction, KD/KO with defined cargo transport phenotype, in vivo validation, single lab\",\n      \"pmids\": [\"35392093\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Crystal structure of the RN-Tre (USP6NL)–RAB43 complex reveals a bipartite recognition mechanism: the RN-Tre N-terminal subdomain catalytically remodels RAB43 Switch regions while the C-terminal subdomain engages Switch II and reorients the hydrophobic triad to confer substrate specificity; Leu146 and C-terminal residues of RN-Tre are key specificity determinants; disease-associated RN-Tre mutations impair GAP activity leading to aberrant Golgi architecture and endocytic trafficking.\",\n      \"method\": \"X-ray crystallography of RN-Tre–RAB43 complex; mutational analysis of specificity determinants; GAP activity assays; Golgi morphology assays with disease-associated mutants\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutational validation plus in vitro GAP activity assays plus cellular functional readouts in one study\",\n      \"pmids\": [\"41401861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"LRRK1 phosphorylates RAB43 at the Switch-II region; this represents a novel kinase:Rab pair identified by in vitro kinase profiling.\",\n      \"method\": \"In vitro kinase profiling of LRRK1, LRRK2, DYRK1A, MST1, and TBK1 against a panel of Rab GTPases\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assay, preprint, no cellular validation for LRRK1:Rab43 pair specifically\",\n      \"pmids\": [\"bio_10.1101_2025.04.09.647999\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"RAB43 promotes ubiquitination and degradation of MyD88 in macrophages; Rab43 KO elevates MyD88 protein levels (by ~80%) without affecting MyD88 mRNA, leading to overactivation of the MAPK-NF-κB pathway; Co-IP confirms RAB43 regulates the interaction of MyD88 with ubiquitin protein, and Rab43 deficiency reduces MyD88-ubiquitin levels by 58% accompanied by downregulation of ubiquitinase genes A20, SPOP, HOIL-1, and OTUD4.\",\n      \"method\": \"Myeloid-specific Rab43 KO mice; LPS-induced ALI model; co-immunoprecipitation; Western blot; qPCR; flow cytometry\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO mouse model, Co-IP for ubiquitin interaction, multiple biochemical readouts, single lab\",\n      \"pmids\": [\"41501355\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RAB43 is a Rab GTPase that localizes to the Golgi apparatus and functions in anterograde ER-to-Golgi trafficking of specific cargo (especially GPCRs and select membrane proteins via direct interaction), retrograde endosome-to-Golgi transport, and maintenance of Golgi structure; it is inactivated by the GAP RN-tre (USP6NL) through a structurally defined bipartite mechanism, can be phosphorylated at its Switch-II region by LRRK1, mediates postsynaptic GPCR targeting in neurons, supports cross-presentation by CD8α+ dendritic cells, controls anterograde transport of CD91 in macrophages to enable efferocytosis, and promotes MyD88 ubiquitination and degradation to restrain TLR4-MyD88-MAPK-NF-κB inflammatory signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RAB43 is a Golgi-localized Rab GTPase that organizes pre-Golgi and trans-Golgi membrane compartments and selectively sorts specific cargo through the secretory pathway [#0, #3, #4]. It maintains functional Golgi architecture: its depletion fragments and disperses the trans-Golgi network, and the GTPase-activating protein RN-tre (USP6NL) inactivates RAB43 and controls retrograde endosome-to-Golgi transport [#0, #2]. A crystal structure of the RN-tre–RAB43 complex defines a bipartite recognition mechanism in which the GAP N-terminal subdomain catalytically remodels the RAB43 Switch regions while the C-terminal subdomain engages Switch II to confer substrate specificity, and disease-associated RN-tre mutations that impair this GAP activity produce aberrant Golgi architecture [#8]. Functionally, RAB43 acts as a cargo-selective trafficking factor: it routes a subset of membrane proteins through the medial Golgi [#4] and drives anterograde ER-to-Golgi transport of nascent GPCRs through direct, activation-dependent receptor binding, a binding domain sufficient to confer RAB43-dependent transport on non-GPCR proteins [#5]. This sorting activity extends to specialized cell types: RAB43 governs dendritic and postsynaptic targeting of α2-adrenergic and muscarinic receptors in neurons via direct interaction [#6], is required for cross-presentation of cell-associated antigens by CD8α+ dendritic cells [#3], mediates anterograde surface transport of CD91 (LRP1) to support macrophage efferocytosis [#7], and restrains TLR4–MyD88–MAPK–NF-κB inflammatory signaling by promoting ubiquitination and degradation of MyD88 in macrophages [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying the GAP for RAB43 established that the protein is a bona fide cycling Rab and placed it as a regulator of retrograde traffic into the Golgi and of Golgi integrity.\",\n      \"evidence\": \"Overexpression screen of 38 human Rab GAPs with Golgi morphology and protein transport readouts, identifying RN-tre (USP6NL) as the RAB43-specific GAP\",\n      \"pmids\": [\"17684057\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the cargo RAB43 transports\", \"Did not identify effectors downstream of active RAB43\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Dominant-negative and overexpression phenotypes localized RAB43 function to the pre-Golgi/ER-exit-site interface and linked it to microtubule-based positioning of Golgi intermediates.\",\n      \"evidence\": \"GFP-RAB43 dominant-negative (T32N) and overexpression with live-cell imaging, VSVG-GFP trafficking, and dynactin p150(Glued) co-localization\",\n      \"pmids\": [\"18664496\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism connecting RAB43 to dynactin not resolved\", \"Single lab; no direct effector identified\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed that RAB43-dependent TGN integrity is functionally required, using HSV-1 secondary envelopment as a sensitive readout of intact trans-Golgi membranes.\",\n      \"evidence\": \"Rab GAP overexpression screen plus RAB43 siRNA with electron microscopy and virion assembly/titer assays\",\n      \"pmids\": [\"21680502\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not establish whether the defect reflects loss of a direct RAB43 cargo or general Golgi disruption\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Two studies converged on RAB43 as a cargo-selective sorter — through the medial Golgi for a subset of membrane proteins and as a requirement for dendritic-cell cross-presentation — moving beyond a purely structural role.\",\n      \"evidence\": \"GFP-RAB43 overexpression/siRNA with glycosylation and surface-delivery cargo assays; germline and conditional Rab43 knockout mice with cross-presentation assays and antibody localization\",\n      \"pmids\": [\"27053659\", \"27899443\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of cargo selectivity not yet defined\", \"Identity of the cross-presentation cargo/compartment not pinned down\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Demonstrated direct, activation-dependent RAB43–GPCR binding and that the receptor RAB43-binding domain is transferable, explaining how RAB43 achieves cargo specificity in anterograde ER-to-Golgi transport.\",\n      \"evidence\": \"Rab siRNA screen for GPCR surface transport, dominant-negative/constitutively-active mutants, Co-IP with multiple GPCRs, and domain-swap chimeras\",\n      \"pmids\": [\"29069590\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of RAB43–receptor recognition not determined\", \"Effector machinery linking bound cargo to vesicle movement unknown\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended the direct-interaction sorting model to neurons, showing RAB43 controls subtype-specific dendritic and postsynaptic receptor targeting and signaling.\",\n      \"evidence\": \"Dominant-negative and CRISPR-Cas9 Rab43 KO in primary neurons with Co-IP, postsynaptic imaging, and signaling assays for α2B-AR and M3 mAChR\",\n      \"pmids\": [\"33676895\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How RAB43 distinguishes dendritic vs somatic routing not resolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified CD91/LRP1 as a RAB43 cargo in macrophages and connected RAB43 expression control to efferocytosis, linking the trafficking activity to a tissue function.\",\n      \"evidence\": \"Co-IP of RAB43 with CD91, knockdown/overexpression surface-localization assays, and Rab43 KO mice in an acute lung injury model\",\n      \"pmids\": [\"35392093\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which HMGB1 suppresses RAB43 expression not detailed\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A crystal structure of the RN-tre–RAB43 complex resolved the bipartite mechanism of GAP specificity and tied disease-associated RN-tre mutations to defective RAB43 inactivation and Golgi/endocytic phenotypes.\",\n      \"evidence\": \"X-ray crystallography of the RN-tre–RAB43 complex with mutational analysis, in vitro GAP assays, and Golgi morphology assays of disease mutants\",\n      \"pmids\": [\"41401861\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of active RAB43 bound to an effector or cargo\", \"GEF for RAB43 not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"An in vitro kinase screen nominated LRRK1 as a kinase phosphorylating RAB43 at Switch II, raising the possibility of kinase-regulated RAB43 cycling.\",\n      \"evidence\": \"In vitro kinase profiling of LRRK1, LRRK2, DYRK1A, MST1, and TBK1 against a Rab GTPase panel (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.04.09.647999\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No cellular validation of LRRK1:RAB43 phosphorylation\", \"Functional consequence of Switch-II phosphorylation unknown\", \"Preprint, not peer-reviewed\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Revealed a signaling-regulatory role: RAB43 promotes MyD88 ubiquitination and degradation to dampen TLR4–MyD88–MAPK–NF-κB inflammatory output in macrophages.\",\n      \"evidence\": \"Myeloid-specific Rab43 KO mice in an LPS-induced ALI model with Co-IP of MyD88–ubiquitin, Western blot, qPCR of deubiquitinase genes, and flow cytometry\",\n      \"pmids\": [\"41501355\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether RAB43 acts directly on MyD88 ubiquitination or via its trafficking activity is unresolved\", \"Mechanism linking RAB43 to ubiquitinase gene expression (A20, SPOP, HOIL-1, OTUD4) unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The activating GEF, the downstream effectors that link cargo-bound RAB43 to vesicle budding/movement, and whether Switch-II phosphorylation regulates RAB43 cycling in cells remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No GEF identified for RAB43\", \"No effector bridging RAB43 to motor/coat machinery characterized\", \"Cellular role of LRRK1-mediated phosphorylation not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [5, 6, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 2, 3, 4]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 4, 5]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [5, 6, 7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [3, 7, 10]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"USP6NL\", \"CD91\", \"MyD88\", \"LRRK1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}