{"gene":"SNX4","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2007,"finding":"SNX4, through its PX and BAR domains, associates with tubular and vesicular elements of early endosomes and the juxtanuclear endocytic recycling compartment (ERC). SNX4 suppression causes lysosomal degradation of the transferrin receptor (TfnR), establishing its role in endosomal sorting and recycling. SNX4 interacts with KIBRA (which binds dynein light chain 1) to associate with the minus-end-directed microtubule motor dynein, linking membrane tubulation-driven cargo sorting to long-range carrier transport from early endosomes to the ERC.","method":"siRNA knockdown, co-immunoprecipitation, fluorescence microscopy, endosomal fractionation","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP for SNX4-KIBRA-dynein interaction, siRNA loss-of-function with defined trafficking phenotype (lysosomal degradation of TfnR), domain-level localization; replicated in multiple follow-up studies","pmids":["17994011"],"is_preprint":false},{"year":2003,"finding":"In yeast, Snx4p (ortholog of SNX4) mediates retrieval of the exocytic v-SNARE Snc1p from post-Golgi endosomes back to the Golgi. Snc1p can be chemically cross-linked to Snx4p. Snx4p physically binds Snx41p and Snx42p, and all three sorting nexins are required for efficient Snc1p sorting, defining a distinct retrieval pathway from early endosomes that is separable from the retromer pathway operating at pre-vacuolar endosomes.","method":"Chemical cross-linking, yeast genetics (deletion mutants), subcellular fractionation, fluorescence microscopy","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct chemical cross-linking of cargo to Snx4p, multiple deletion mutants with defined phenotypes, replicated by subsequent studies","pmids":["12554655"],"is_preprint":false},{"year":2009,"finding":"SNX4 forms complexes with clathrin and dynein on endosomes; these interactions depend on PI3-kinase activity (inhibited by wortmannin), indicating they occur when SNX4 is PI(3)P-associated. A clathrin-box variant motif on SNX4 was identified as the clathrin-interacting site; a short peptide containing this motif is sufficient to pull down both clathrin and dynein. Clathrin knockdown is not required for the SNX4/dynein interaction but leads to increased retrograde Golgi transport of ricin and redistribution of endosomes, suggesting clathrin regulates SNX4-dependent transport.","method":"Co-immunoprecipitation, peptide pulldown, siRNA knockdown, pharmacological inhibition (wortmannin), fluorescence microscopy, toxin trafficking assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — peptide pulldown identifies clathrin-box motif, Co-IP and pharmacological inhibition, single lab with two orthogonal methods","pmids":["19529763"],"is_preprint":false},{"year":2013,"finding":"Reggie-1 (flotillin-2) directly interacts with SNX4 and Rab11a at the tubulovesicular recycling compartment. Reggie-1 depletion impairs TfR recycling to the plasma membrane and E-cadherin recycling after internalization; both defects are rescued by overexpression of constitutively active Rab11a or SNX4, placing reggie-1 as a regulator upstream of the Rab11a/SNX4-controlled recycling pathway.","method":"Co-immunoprecipitation (direct interaction), shRNA knockdown, overexpression rescue experiments, fluorescence microscopy","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct Co-IP plus genetic rescue experiments, single lab, two orthogonal methods","pmids":["23825023"],"is_preprint":false},{"year":2017,"finding":"Yeast Snx4 forms two functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats a distinct endosome-derived tubule mediating retrograde sorting of different cargo: Snc1 is sorted by Snx4-Atg20, and Atg27 is sorted by Snx4-Snx41. The dynamin-family GTPase Vps1, which promotes fission of retromer-coated tubules, also promotes fission of Snx4-Atg20-coated tubules, linking tubule scission to Snx4-dependent retrograde trafficking.","method":"Live-cell fluorescence microscopy, genetic deletion, cargo-specific trafficking assays, co-localization","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging of distinct tubules, cargo-specific trafficking assays with deletions, single lab","pmids":["28026081"],"is_preprint":false},{"year":2017,"finding":"Yeast Snx4 cooperates with Snx41 and Snx42 to mediate autophagic turnover of the 26S proteasome and other large multisubunit complexes during nitrogen starvation. Snx4 is required for the formation of cytoplasmic proteasome puncta that accumulate when autophagosome formation is blocked, placing Snx4 at the step of cytoplasmic agglomeration of proteasomes prior to autophagic delivery.","method":"Yeast deletion mutants, fluorescence microscopy, pharmacological tethering, targeted autophagy gene screen","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — targeted genetic screen, fluorescence microscopy with proteasome puncta as readout, single lab with multiple orthogonal approaches","pmids":["29109144"],"is_preprint":false},{"year":2020,"finding":"In mammalian cells, SNX4 is required for efficient LC3 lipidation and autophagosome assembly. SNX4 forms functional heterodimers with either SNX7 or SNX30 on tubulovesicular endocytic membranes. SNX4-SNX7 is an autophagy-specific heterodimer required for recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localizes with juxtanuclear ATG9A-positive membranes, and SNX4 disruption causes mis-trafficking/retention of ATG9A in the Golgi region, linking the SNX4-SNX7 complex to ATG9A trafficking during autophagosome assembly.","method":"siRNA knockdown, CRISPR-Cas9 knockout, quantitative fluorescence microscopy, co-immunoprecipitation (heterodimer identification)","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO and siRNA with defined autophagy phenotype, heterodimer identification by Co-IP, image-based ATG9A trafficking analysis; two orthogonal genetic tools in single study","pmids":["32513819"],"is_preprint":false},{"year":2021,"finding":"SNX4 mediates recycling of the lipid scramblase ATG9A from endolysosomes to early endosomes, from where ATG9A is further recycled to the trans-Golgi network in a retromer (VPS35)-dependent manner. SNX4 depletion causes accumulation of ATG9A on endolysosomes; VPS35 depletion causes accumulation on early endosomes. SNX4-mediated ATG9A recycling is required for starvation-induced autophagosome biogenesis and autophagic flux, likely by preventing exhaustion of the ATG9A pool.","method":"siRNA knockdown, fluorescence microscopy, autophagy flux assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with compartment-specific ATG9A accumulation as readout plus autophagic flux assay, two orthogonal readouts, single lab","pmids":["33468622"],"is_preprint":false},{"year":2021,"finding":"In yeast, the sorting nexin heterodimer Snx4/Atg24-Atg20 is required for a selective autophagy pathway (Snx4-assisted autophagy of transcription factors, SAA-TF) that targets transcriptional regulators Ssn2/Med13, Rim15, and Msn2 for vacuolar proteolysis upon nitrogen starvation. Snx4-Atg20 binds Atg17, relocates to the perinucleus upon starvation, and is required for efficient transfer of cargo (Ssn2/Med13) to Atg17-initiated phagophores anchored to the vacuole.","method":"Yeast genetics (deletion analysis), fluorescence microscopy, co-immunoprecipitation","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic deletions with specific cargo degradation readouts, Co-IP for Snx4-Atg17 interaction, single lab","pmids":["33678121"],"is_preprint":false},{"year":2024,"finding":"In yeast, the Snx4-Atg20 heterodimer delivers the cargo Ssn2/Med13 to phagophores in the SAA-TF pathway. Ksp1, an autophagic receptor, is recruited early to phagophores via Atg29 independently of both Atg8 and Snx4; Snx4 delivers Ssn2/Med13 to phagophores thereafter, defining the temporal order of receptor and cargo delivery in this pathway.","method":"Yeast two-hybrid, genetic deletion analysis, fluorescence microscopy, mutagenesis of AIM/LIR motifs","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis combined with mutagenesis of interaction motifs to order pathway steps, single lab","pmids":["37733395"],"is_preprint":false},{"year":2024,"finding":"In neurons, SNX4 conditional knockout leads to an increase in docked synaptic vesicles at the active zone and decreased active zone length, resulting in increased docked vesicle density per release site. This causes enhanced neurotransmission during train stimulation without affecting vesicle recycling, autophagic flux, or VAMP2/synaptobrevin-2 levels or localization, establishing SNX4 as a negative regulator of synaptic vesicle docking and release.","method":"Conditional knockout mouse model, electron microscopy (ultrastructure), electrophysiology (evoked EPSCs), Western blot, fluorescence microscopy","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with ultrastructural (EM) and functional (electrophysiology) readouts, multiple orthogonal methods, defined phenotype at synaptic vesicle docking","pmids":["39699951"],"is_preprint":false}],"current_model":"SNX4 is a PI(3)P-binding SNX-BAR protein that functions as an endosomal sorting and recycling coordinator: it drives membrane tubulation on early endosomes/recycling compartments (via its PX and BAR domains) to sort cargo such as the transferrin receptor, associates with dynein (via KIBRA) and clathrin for long-range carrier transport, forms functionally distinct heterodimers (with SNX7/SNX30 in mammals, or Snx41/Atg20 in yeast) that mediate retrograde trafficking of specific cargoes (TfnR, Snc1, Atg27) and ATG9A recycling from endolysosomes to sustain autophagosome biogenesis; in yeast it additionally mediates selective autophagy of proteasomes and transcription factors via a complex with Atg17 and Atg20, and in neurons it limits synaptic vesicle docking and neurotransmitter release."},"narrative":{"mechanistic_narrative":"SNX4 is a PI(3)P-associated sorting nexin that coordinates endosomal cargo sorting, tubulation-driven membrane recycling, and autophagosome biogenesis [PMID:17994011, PMID:32513819]. Through its PX and BAR domains it associates with tubular and vesicular elements of early endosomes and the juxtanuclear endocytic recycling compartment, where it sorts cargo such as the transferrin receptor away from lysosomal degradation [PMID:17994011]. SNX4 couples this tubulation-based sorting to long-range microtubule-based transport by interacting with KIBRA to engage minus-end-directed dynein and by binding clathrin through a clathrin-box variant motif, with both interactions dependent on PI3-kinase activity [PMID:17994011, PMID:19529763]. In yeast the ortholog forms two functionally distinct heterodimers, Snx4-Atg20 and Snx4-Snx41, that coat separate endosome-derived tubules to retrieve distinct cargoes (Snc1 and Atg27), with Vps1 promoting tubule fission [PMID:12554655, PMID:28026081]. In mammalian cells SNX4 assembles analogous heterodimers with SNX7 or SNX30; the autophagy-specific SNX4-SNX7 complex supports LC3 lipidation and recycles the lipid scramblase ATG9A from endolysosomes to early endosomes, sustaining the ATG9A pool required for starvation-induced autophagosome assembly [PMID:32513819, PMID:33468622]. In yeast SNX4 additionally drives selective autophagy of the 26S proteasome and of transcription factors (Ssn2/Med13, Rim15, Msn2) by delivering cargo to Atg17-initiated phagophores [PMID:29109144, PMID:33678121, PMID:37733395]. In neurons SNX4 acts as a negative regulator of synaptic vesicle docking, limiting docked vesicle density and neurotransmitter release at the active zone [PMID:39699951].","teleology":[{"year":2003,"claim":"Established that the SNX4 ortholog defines a retromer-independent retrieval route, answering whether SNX4-family proteins sort specific cargo back to the Golgi from early endosomes.","evidence":"Chemical cross-linking of Snc1p to Snx4p with yeast deletion mutants and fractionation","pmids":["12554655"],"confidence":"High","gaps":["Did not define the structural basis of cargo selection","Mammalian relevance not established at this point"]},{"year":2007,"claim":"Defined SNX4 as an endosomal sorting/recycling factor that protects the transferrin receptor from degradation and linked its membrane tubulation to dynein-based transport, answering how sorted cargo reaches the recycling compartment.","evidence":"siRNA knockdown with TfnR degradation phenotype plus reciprocal Co-IP of SNX4-KIBRA-dynein in mammalian cells","pmids":["17994011"],"confidence":"High","gaps":["Mechanism of KIBRA-mediated motor recruitment not resolved at molecular level","Did not address autophagy roles"]},{"year":2009,"claim":"Identified the clathrin-binding determinant on SNX4 and showed PI3-kinase dependence of its dynein/clathrin associations, clarifying how SNX4 carrier transport is regulated.","evidence":"Peptide pulldown defining a clathrin-box variant motif, Co-IP, and wortmannin inhibition with toxin trafficking assays","pmids":["19529763"],"confidence":"Medium","gaps":["Single lab","Functional consequence of clathrin regulation on physiological cargo not fully defined"]},{"year":2013,"claim":"Placed reggie-1/flotillin-2 upstream of the Rab11a/SNX4 recycling pathway, addressing what regulates SNX4-dependent recycling of TfR and E-cadherin.","evidence":"Direct Co-IP plus shRNA knockdown with overexpression rescue by Rab11a or SNX4 in mammalian cells","pmids":["23825023"],"confidence":"Medium","gaps":["Single lab","Direct biochemical hierarchy among reggie-1, Rab11a, and SNX4 not fully resolved"]},{"year":2017,"claim":"Resolved SNX4 into two cargo-specific heterodimers and linked their tubules to Vps1-mediated fission, answering how a single nexin sorts distinct cargoes.","evidence":"Live-cell imaging of distinct tubules with cargo-specific trafficking assays and deletions in yeast","pmids":["28026081"],"confidence":"Medium","gaps":["Single lab","Did not establish whether mammalian heterodimers segregate cargo identically"]},{"year":2017,"claim":"Extended SNX4 function to selective autophagy of large complexes by showing it is required for cytoplasmic proteasome agglomeration prior to autophagic delivery.","evidence":"Targeted autophagy gene screen and fluorescence microscopy with proteasome puncta readout in yeast","pmids":["29109144"],"confidence":"Medium","gaps":["Mechanism of proteasome capture by Snx4 not defined","Single organism"]},{"year":2020,"claim":"Established the mammalian SNX4-SNX7 heterodimer as an autophagy-specific complex required for LC3 lipidation and proper ATG9A trafficking, answering whether SNX4 contributes to autophagosome assembly in human cells.","evidence":"CRISPR knockout and siRNA with autophagy phenotypes, Co-IP heterodimer identification, and ATG9A imaging","pmids":["32513819"],"confidence":"High","gaps":["Did not define the precise membrane source supported by SNX4-SNX7","Structural basis of heterodimer specificity unresolved"]},{"year":2021,"claim":"Defined the directionality of SNX4-dependent ATG9A recycling (endolysosome to early endosome, then retromer to TGN), explaining how SNX4 sustains the ATG9A pool for autophagy.","evidence":"siRNA knockdown with compartment-specific ATG9A accumulation and autophagic flux assays","pmids":["33468622"],"confidence":"Medium","gaps":["Single lab","Did not resolve how SNX4 and retromer hand off ATG9A"]},{"year":2021,"claim":"Defined a selective autophagy pathway (SAA-TF) in which Snx4-Atg20 binds Atg17 and delivers transcription-factor cargo to vacuole-anchored phagophores.","evidence":"Yeast deletion analysis, fluorescence microscopy, and Co-IP for Snx4-Atg17 interaction","pmids":["33678121"],"confidence":"Medium","gaps":["Single lab","Cargo recognition mechanism for individual transcription factors not defined"]},{"year":2024,"claim":"Ordered the temporal steps of the SAA-TF pathway, showing receptor (Ksp1) recruitment precedes Snx4-mediated cargo delivery to phagophores.","evidence":"Yeast two-hybrid, genetic epistasis, and AIM/LIR motif mutagenesis in yeast","pmids":["37733395"],"confidence":"Medium","gaps":["Single lab","Conservation of this temporal logic in mammals unknown"]},{"year":2024,"claim":"Revealed a neuron-specific role, establishing SNX4 as a negative regulator of synaptic vesicle docking and neurotransmitter release independent of its autophagy and recycling roles.","evidence":"Conditional knockout mouse with EM ultrastructure and electrophysiology of evoked release","pmids":["39699951"],"confidence":"High","gaps":["Molecular mechanism by which SNX4 restrains docking not defined","Cargo or partner mediating active-zone effect unidentified"]},{"year":null,"claim":"How SNX4 heterodimer composition, lipid binding, and partner engagement are switched between its recycling, autophagy, and synaptic-regulatory functions remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model connecting heterodimer choice to cargo selection","Mechanism linking SNX4 to synaptic vesicle docking unknown","Integration of dynein/clathrin transport with autophagic membrane supply not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[0,2]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,4,6]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,1,4,6,7]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[7]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,6]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,6]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[5,6,7,8]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,2,4]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,3,7]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[10]}],"complexes":["SNX4-SNX7 heterodimer","SNX4-SNX30 heterodimer","Snx4-Atg20 heterodimer","Snx4-Snx41 heterodimer"],"partners":["KIBRA","CLATHRIN","DYNEIN","SNX7","SNX30","ATG20","SNX41","ATG17"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95219","full_name":"Sorting nexin-4","aliases":[],"length_aa":450,"mass_kda":51.9,"function":"Involved in the regulation of endocytosis and in several stages of intracellular trafficking (PubMed:12668730, PubMed:17994011, PubMed:32513819, PubMed:33468622). Plays a role in recycling endocytosed transferrin receptor and prevent its degradation (PubMed:17994011). Involved in autophagosome assembly by regulating trafficking and recycling of phospholipid scramblase ATG9A (PubMed:32513819, PubMed:33468622)","subcellular_location":"Early endosome membrane","url":"https://www.uniprot.org/uniprotkb/O95219/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SNX4","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000114520","cell_line_id":"CID000681","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":2}],"interactors":[{"gene":"SNX7","stoichiometry":10.0},{"gene":"SNX30","stoichiometry":10.0},{"gene":"PIP5K1C","stoichiometry":0.2},{"gene":"SNX2","stoichiometry":0.2},{"gene":"NPEPPS","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000681","total_profiled":1310},"omim":[{"mim_id":"621073","title":"SORTING NEXIN 32; SNX32","url":"https://www.omim.org/entry/621073"},{"mim_id":"620955","title":"SORTING NEXIN 30; SNX30","url":"https://www.omim.org/entry/620955"},{"mim_id":"614904","title":"SORTING NEXIN 7; SNX7","url":"https://www.omim.org/entry/614904"},{"mim_id":"606098","title":"SORTING NEXIN 6; SNX6","url":"https://www.omim.org/entry/606098"},{"mim_id":"605964","title":"SORTING NEXIN 15; SNX15","url":"https://www.omim.org/entry/605964"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SNX4"},"hgnc":{"alias_symbol":["ATG24B"],"prev_symbol":[]},"alphafold":{"accession":"O95219","domains":[{"cath_id":"1.20.1270.60","chopping":"201-348_369-450","consensus_level":"medium","plddt":94.063,"start":201,"end":450}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95219","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95219-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95219-F1-predicted_aligned_error_v6.png","plddt_mean":83.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNX4","jax_strain_url":"https://www.jax.org/strain/search?query=SNX4"},"sequence":{"accession":"O95219","fasta_url":"https://rest.uniprot.org/uniprotkb/O95219.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95219/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95219"}},"corpus_meta":[{"pmid":"17994011","id":"PMC_17994011","title":"SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment.","date":"2007","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17994011","citation_count":222,"is_preprint":false},{"pmid":"12554655","id":"PMC_12554655","title":"Retromer and the sorting nexins Snx4/41/42 mediate distinct retrieval pathways from yeast endosomes.","date":"2003","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/12554655","citation_count":175,"is_preprint":false},{"pmid":"23825023","id":"PMC_23825023","title":"Reggies/flotillins interact with Rab11a and SNX4 at the tubulovesicular recycling compartment and function in transferrin receptor and E-cadherin trafficking.","date":"2013","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23825023","citation_count":65,"is_preprint":false},{"pmid":"29109144","id":"PMC_29109144","title":"Autophagic clearance of proteasomes in yeast requires the conserved sorting nexin Snx4.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29109144","citation_count":65,"is_preprint":false},{"pmid":"28026081","id":"PMC_28026081","title":"Distinct complexes of yeast Snx4 family SNX-BARs mediate retrograde trafficking of Snc1 and Atg27.","date":"2017","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/28026081","citation_count":52,"is_preprint":false},{"pmid":"32513819","id":"PMC_32513819","title":"A heterodimeric SNX4--SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/32513819","citation_count":37,"is_preprint":false},{"pmid":"19529763","id":"PMC_19529763","title":"SNX4 in complex with clathrin and dynein: implications for endosome movement.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19529763","citation_count":35,"is_preprint":false},{"pmid":"33468622","id":"PMC_33468622","title":"The phosphatidylinositol 3-phosphate-binding protein SNX4 controls ATG9A recycling and autophagy.","date":"2021","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/33468622","citation_count":33,"is_preprint":false},{"pmid":"33678121","id":"PMC_33678121","title":"Snx4-assisted vacuolar targeting of transcription factors defines a new autophagy pathway for controlling ATG expression.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/33678121","citation_count":15,"is_preprint":false},{"pmid":"37733395","id":"PMC_37733395","title":"Ksp1 is an autophagic receptor protein for the Snx4-assisted autophagy of Ssn2/Med13.","date":"2024","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/37733395","citation_count":5,"is_preprint":false},{"pmid":"39699951","id":"PMC_39699951","title":"Endosomal sorting protein SNX4 limits synaptic vesicle docking and release.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/39699951","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.04.657876","title":"Neurotrophic Factor-α1/carboxypeptidase E regulates critical protein networks to rescue neurodegeneration, defective synaptogenesis and impaired autophagy in Alzheimer’s Disease mice","date":"2025-06-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.04.657876","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8472,"output_tokens":3386,"usd":0.038103,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10872,"output_tokens":3812,"usd":0.07483,"stage2_stop_reason":"end_turn"},"total_usd":0.112933,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"SNX4, through its PX and BAR domains, associates with tubular and vesicular elements of early endosomes and the juxtanuclear endocytic recycling compartment (ERC). SNX4 suppression causes lysosomal degradation of the transferrin receptor (TfnR), establishing its role in endosomal sorting and recycling. SNX4 interacts with KIBRA (which binds dynein light chain 1) to associate with the minus-end-directed microtubule motor dynein, linking membrane tubulation-driven cargo sorting to long-range carrier transport from early endosomes to the ERC.\",\n      \"method\": \"siRNA knockdown, co-immunoprecipitation, fluorescence microscopy, endosomal fractionation\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP for SNX4-KIBRA-dynein interaction, siRNA loss-of-function with defined trafficking phenotype (lysosomal degradation of TfnR), domain-level localization; replicated in multiple follow-up studies\",\n      \"pmids\": [\"17994011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"In yeast, Snx4p (ortholog of SNX4) mediates retrieval of the exocytic v-SNARE Snc1p from post-Golgi endosomes back to the Golgi. Snc1p can be chemically cross-linked to Snx4p. Snx4p physically binds Snx41p and Snx42p, and all three sorting nexins are required for efficient Snc1p sorting, defining a distinct retrieval pathway from early endosomes that is separable from the retromer pathway operating at pre-vacuolar endosomes.\",\n      \"method\": \"Chemical cross-linking, yeast genetics (deletion mutants), subcellular fractionation, fluorescence microscopy\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct chemical cross-linking of cargo to Snx4p, multiple deletion mutants with defined phenotypes, replicated by subsequent studies\",\n      \"pmids\": [\"12554655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"SNX4 forms complexes with clathrin and dynein on endosomes; these interactions depend on PI3-kinase activity (inhibited by wortmannin), indicating they occur when SNX4 is PI(3)P-associated. A clathrin-box variant motif on SNX4 was identified as the clathrin-interacting site; a short peptide containing this motif is sufficient to pull down both clathrin and dynein. Clathrin knockdown is not required for the SNX4/dynein interaction but leads to increased retrograde Golgi transport of ricin and redistribution of endosomes, suggesting clathrin regulates SNX4-dependent transport.\",\n      \"method\": \"Co-immunoprecipitation, peptide pulldown, siRNA knockdown, pharmacological inhibition (wortmannin), fluorescence microscopy, toxin trafficking assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — peptide pulldown identifies clathrin-box motif, Co-IP and pharmacological inhibition, single lab with two orthogonal methods\",\n      \"pmids\": [\"19529763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Reggie-1 (flotillin-2) directly interacts with SNX4 and Rab11a at the tubulovesicular recycling compartment. Reggie-1 depletion impairs TfR recycling to the plasma membrane and E-cadherin recycling after internalization; both defects are rescued by overexpression of constitutively active Rab11a or SNX4, placing reggie-1 as a regulator upstream of the Rab11a/SNX4-controlled recycling pathway.\",\n      \"method\": \"Co-immunoprecipitation (direct interaction), shRNA knockdown, overexpression rescue experiments, fluorescence microscopy\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct Co-IP plus genetic rescue experiments, single lab, two orthogonal methods\",\n      \"pmids\": [\"23825023\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Yeast Snx4 forms two functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats a distinct endosome-derived tubule mediating retrograde sorting of different cargo: Snc1 is sorted by Snx4-Atg20, and Atg27 is sorted by Snx4-Snx41. The dynamin-family GTPase Vps1, which promotes fission of retromer-coated tubules, also promotes fission of Snx4-Atg20-coated tubules, linking tubule scission to Snx4-dependent retrograde trafficking.\",\n      \"method\": \"Live-cell fluorescence microscopy, genetic deletion, cargo-specific trafficking assays, co-localization\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging of distinct tubules, cargo-specific trafficking assays with deletions, single lab\",\n      \"pmids\": [\"28026081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Yeast Snx4 cooperates with Snx41 and Snx42 to mediate autophagic turnover of the 26S proteasome and other large multisubunit complexes during nitrogen starvation. Snx4 is required for the formation of cytoplasmic proteasome puncta that accumulate when autophagosome formation is blocked, placing Snx4 at the step of cytoplasmic agglomeration of proteasomes prior to autophagic delivery.\",\n      \"method\": \"Yeast deletion mutants, fluorescence microscopy, pharmacological tethering, targeted autophagy gene screen\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — targeted genetic screen, fluorescence microscopy with proteasome puncta as readout, single lab with multiple orthogonal approaches\",\n      \"pmids\": [\"29109144\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In mammalian cells, SNX4 is required for efficient LC3 lipidation and autophagosome assembly. SNX4 forms functional heterodimers with either SNX7 or SNX30 on tubulovesicular endocytic membranes. SNX4-SNX7 is an autophagy-specific heterodimer required for recruitment/retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially co-localizes with juxtanuclear ATG9A-positive membranes, and SNX4 disruption causes mis-trafficking/retention of ATG9A in the Golgi region, linking the SNX4-SNX7 complex to ATG9A trafficking during autophagosome assembly.\",\n      \"method\": \"siRNA knockdown, CRISPR-Cas9 knockout, quantitative fluorescence microscopy, co-immunoprecipitation (heterodimer identification)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO and siRNA with defined autophagy phenotype, heterodimer identification by Co-IP, image-based ATG9A trafficking analysis; two orthogonal genetic tools in single study\",\n      \"pmids\": [\"32513819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SNX4 mediates recycling of the lipid scramblase ATG9A from endolysosomes to early endosomes, from where ATG9A is further recycled to the trans-Golgi network in a retromer (VPS35)-dependent manner. SNX4 depletion causes accumulation of ATG9A on endolysosomes; VPS35 depletion causes accumulation on early endosomes. SNX4-mediated ATG9A recycling is required for starvation-induced autophagosome biogenesis and autophagic flux, likely by preventing exhaustion of the ATG9A pool.\",\n      \"method\": \"siRNA knockdown, fluorescence microscopy, autophagy flux assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with compartment-specific ATG9A accumulation as readout plus autophagic flux assay, two orthogonal readouts, single lab\",\n      \"pmids\": [\"33468622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In yeast, the sorting nexin heterodimer Snx4/Atg24-Atg20 is required for a selective autophagy pathway (Snx4-assisted autophagy of transcription factors, SAA-TF) that targets transcriptional regulators Ssn2/Med13, Rim15, and Msn2 for vacuolar proteolysis upon nitrogen starvation. Snx4-Atg20 binds Atg17, relocates to the perinucleus upon starvation, and is required for efficient transfer of cargo (Ssn2/Med13) to Atg17-initiated phagophores anchored to the vacuole.\",\n      \"method\": \"Yeast genetics (deletion analysis), fluorescence microscopy, co-immunoprecipitation\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic deletions with specific cargo degradation readouts, Co-IP for Snx4-Atg17 interaction, single lab\",\n      \"pmids\": [\"33678121\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In yeast, the Snx4-Atg20 heterodimer delivers the cargo Ssn2/Med13 to phagophores in the SAA-TF pathway. Ksp1, an autophagic receptor, is recruited early to phagophores via Atg29 independently of both Atg8 and Snx4; Snx4 delivers Ssn2/Med13 to phagophores thereafter, defining the temporal order of receptor and cargo delivery in this pathway.\",\n      \"method\": \"Yeast two-hybrid, genetic deletion analysis, fluorescence microscopy, mutagenesis of AIM/LIR motifs\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis combined with mutagenesis of interaction motifs to order pathway steps, single lab\",\n      \"pmids\": [\"37733395\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In neurons, SNX4 conditional knockout leads to an increase in docked synaptic vesicles at the active zone and decreased active zone length, resulting in increased docked vesicle density per release site. This causes enhanced neurotransmission during train stimulation without affecting vesicle recycling, autophagic flux, or VAMP2/synaptobrevin-2 levels or localization, establishing SNX4 as a negative regulator of synaptic vesicle docking and release.\",\n      \"method\": \"Conditional knockout mouse model, electron microscopy (ultrastructure), electrophysiology (evoked EPSCs), Western blot, fluorescence microscopy\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with ultrastructural (EM) and functional (electrophysiology) readouts, multiple orthogonal methods, defined phenotype at synaptic vesicle docking\",\n      \"pmids\": [\"39699951\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNX4 is a PI(3)P-binding SNX-BAR protein that functions as an endosomal sorting and recycling coordinator: it drives membrane tubulation on early endosomes/recycling compartments (via its PX and BAR domains) to sort cargo such as the transferrin receptor, associates with dynein (via KIBRA) and clathrin for long-range carrier transport, forms functionally distinct heterodimers (with SNX7/SNX30 in mammals, or Snx41/Atg20 in yeast) that mediate retrograde trafficking of specific cargoes (TfnR, Snc1, Atg27) and ATG9A recycling from endolysosomes to sustain autophagosome biogenesis; in yeast it additionally mediates selective autophagy of proteasomes and transcription factors via a complex with Atg17 and Atg20, and in neurons it limits synaptic vesicle docking and neurotransmitter release.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNX4 is a PI(3)P-associated sorting nexin that coordinates endosomal cargo sorting, tubulation-driven membrane recycling, and autophagosome biogenesis [#0, #6]. Through its PX and BAR domains it associates with tubular and vesicular elements of early endosomes and the juxtanuclear endocytic recycling compartment, where it sorts cargo such as the transferrin receptor away from lysosomal degradation [#0]. SNX4 couples this tubulation-based sorting to long-range microtubule-based transport by interacting with KIBRA to engage minus-end-directed dynein and by binding clathrin through a clathrin-box variant motif, with both interactions dependent on PI3-kinase activity [#0, #2]. In yeast the ortholog forms two functionally distinct heterodimers, Snx4-Atg20 and Snx4-Snx41, that coat separate endosome-derived tubules to retrieve distinct cargoes (Snc1 and Atg27), with Vps1 promoting tubule fission [#1, #4]. In mammalian cells SNX4 assembles analogous heterodimers with SNX7 or SNX30; the autophagy-specific SNX4-SNX7 complex supports LC3 lipidation and recycles the lipid scramblase ATG9A from endolysosomes to early endosomes, sustaining the ATG9A pool required for starvation-induced autophagosome assembly [#6, #7]. In yeast SNX4 additionally drives selective autophagy of the 26S proteasome and of transcription factors (Ssn2/Med13, Rim15, Msn2) by delivering cargo to Atg17-initiated phagophores [#5, #8, #9]. In neurons SNX4 acts as a negative regulator of synaptic vesicle docking, limiting docked vesicle density and neurotransmitter release at the active zone [#10].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that the SNX4 ortholog defines a retromer-independent retrieval route, answering whether SNX4-family proteins sort specific cargo back to the Golgi from early endosomes.\",\n      \"evidence\": \"Chemical cross-linking of Snc1p to Snx4p with yeast deletion mutants and fractionation\",\n      \"pmids\": [\"12554655\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the structural basis of cargo selection\", \"Mammalian relevance not established at this point\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Defined SNX4 as an endosomal sorting/recycling factor that protects the transferrin receptor from degradation and linked its membrane tubulation to dynein-based transport, answering how sorted cargo reaches the recycling compartment.\",\n      \"evidence\": \"siRNA knockdown with TfnR degradation phenotype plus reciprocal Co-IP of SNX4-KIBRA-dynein in mammalian cells\",\n      \"pmids\": [\"17994011\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of KIBRA-mediated motor recruitment not resolved at molecular level\", \"Did not address autophagy roles\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identified the clathrin-binding determinant on SNX4 and showed PI3-kinase dependence of its dynein/clathrin associations, clarifying how SNX4 carrier transport is regulated.\",\n      \"evidence\": \"Peptide pulldown defining a clathrin-box variant motif, Co-IP, and wortmannin inhibition with toxin trafficking assays\",\n      \"pmids\": [\"19529763\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Functional consequence of clathrin regulation on physiological cargo not fully defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed reggie-1/flotillin-2 upstream of the Rab11a/SNX4 recycling pathway, addressing what regulates SNX4-dependent recycling of TfR and E-cadherin.\",\n      \"evidence\": \"Direct Co-IP plus shRNA knockdown with overexpression rescue by Rab11a or SNX4 in mammalian cells\",\n      \"pmids\": [\"23825023\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct biochemical hierarchy among reggie-1, Rab11a, and SNX4 not fully resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolved SNX4 into two cargo-specific heterodimers and linked their tubules to Vps1-mediated fission, answering how a single nexin sorts distinct cargoes.\",\n      \"evidence\": \"Live-cell imaging of distinct tubules with cargo-specific trafficking assays and deletions in yeast\",\n      \"pmids\": [\"28026081\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Did not establish whether mammalian heterodimers segregate cargo identically\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Extended SNX4 function to selective autophagy of large complexes by showing it is required for cytoplasmic proteasome agglomeration prior to autophagic delivery.\",\n      \"evidence\": \"Targeted autophagy gene screen and fluorescence microscopy with proteasome puncta readout in yeast\",\n      \"pmids\": [\"29109144\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of proteasome capture by Snx4 not defined\", \"Single organism\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Established the mammalian SNX4-SNX7 heterodimer as an autophagy-specific complex required for LC3 lipidation and proper ATG9A trafficking, answering whether SNX4 contributes to autophagosome assembly in human cells.\",\n      \"evidence\": \"CRISPR knockout and siRNA with autophagy phenotypes, Co-IP heterodimer identification, and ATG9A imaging\",\n      \"pmids\": [\"32513819\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the precise membrane source supported by SNX4-SNX7\", \"Structural basis of heterodimer specificity unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined the directionality of SNX4-dependent ATG9A recycling (endolysosome to early endosome, then retromer to TGN), explaining how SNX4 sustains the ATG9A pool for autophagy.\",\n      \"evidence\": \"siRNA knockdown with compartment-specific ATG9A accumulation and autophagic flux assays\",\n      \"pmids\": [\"33468622\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Did not resolve how SNX4 and retromer hand off ATG9A\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined a selective autophagy pathway (SAA-TF) in which Snx4-Atg20 binds Atg17 and delivers transcription-factor cargo to vacuole-anchored phagophores.\",\n      \"evidence\": \"Yeast deletion analysis, fluorescence microscopy, and Co-IP for Snx4-Atg17 interaction\",\n      \"pmids\": [\"33678121\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Cargo recognition mechanism for individual transcription factors not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Ordered the temporal steps of the SAA-TF pathway, showing receptor (Ksp1) recruitment precedes Snx4-mediated cargo delivery to phagophores.\",\n      \"evidence\": \"Yeast two-hybrid, genetic epistasis, and AIM/LIR motif mutagenesis in yeast\",\n      \"pmids\": [\"37733395\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Conservation of this temporal logic in mammals unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a neuron-specific role, establishing SNX4 as a negative regulator of synaptic vesicle docking and neurotransmitter release independent of its autophagy and recycling roles.\",\n      \"evidence\": \"Conditional knockout mouse with EM ultrastructure and electrophysiology of evoked release\",\n      \"pmids\": [\"39699951\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which SNX4 restrains docking not defined\", \"Cargo or partner mediating active-zone effect unidentified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SNX4 heterodimer composition, lipid binding, and partner engagement are switched between its recycling, autophagy, and synaptic-regulatory functions remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model connecting heterodimer choice to cargo selection\", \"Mechanism linking SNX4 to synaptic vesicle docking unknown\", \"Integration of dynein/clathrin transport with autophagic membrane supply not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 4, 6]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 1, 4, 6, 7]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 6]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [5, 6, 7, 8]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 2, 4]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 3, 7]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"SNX4-SNX7 heterodimer\",\n      \"SNX4-SNX30 heterodimer\",\n      \"Snx4-Atg20 heterodimer\",\n      \"Snx4-Snx41 heterodimer\"\n    ],\n    \"partners\": [\n      \"KIBRA\",\n      \"clathrin\",\n      \"dynein\",\n      \"SNX7\",\n      \"SNX30\",\n      \"Atg20\",\n      \"Snx41\",\n      \"Atg17\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}