{"gene":"SNX20","run_date":"2026-06-10T07:46:37","timeline":{"discoveries":[{"year":2008,"finding":"SLIC-1/SNX20 directly interacts with the cytoplasmic domain of PSGL-1, as identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation and motif mapping.","method":"Yeast two-hybrid screen, co-immunoprecipitation, motif mapping","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with motif mapping, single lab, two orthogonal methods","pmids":["18196517"],"is_preprint":false},{"year":2008,"finding":"SLIC-1/SNX20 contains a Phox homology (PX) domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes, as demonstrated by colocalization experiments.","method":"Colocalization experiments, subcellular fractionation/imaging","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — colocalization established endosomal targeting, single lab but supported by known PX-domain phosphoinositide binding function and motif mapping","pmids":["18196517"],"is_preprint":false},{"year":2008,"finding":"Deficiency of the murine homologue of SLIC-1/SNX20 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1, indicating that SNX20 functions as a sorting molecule cycling PSGL-1 into endosomes without impacting leukocyte recruitment.","method":"Knockout mouse model, neutrophil adhesion assays, signaling assays","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function in vivo with defined cellular phenotype readouts, single lab","pmids":["18196517"],"is_preprint":false},{"year":2018,"finding":"SNX20 and SNX21 are classified as SNX-PXB proteins based on the presence of a PX-associated B (PXB) domain, predicted to function as endosome-associated scaffolds; this paper established the SNX21 interactome but did not directly characterize SNX20 binding partners.","method":"Unbiased quantitative proteomics (for SNX21); classification of SNX20 as SNX-PXB protein by domain analysis","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 4 / Weak — SNX20 classification is domain-prediction based; no direct experiment performed on SNX20 in this paper","pmids":["30072438"],"is_preprint":false}],"current_model":"SNX20 (SLIC-1) is an endosomal sorting nexin that uses its PX domain to bind phosphoinositides and target the PSGL-1/SNX20 complex to endosomes; it directly interacts with the cytoplasmic domain of PSGL-1 but loss of SNX20 does not affect PSGL-1-dependent signaling or neutrophil adhesion, indicating its role is confined to endosomal recycling/sorting of PSGL-1 rather than outside-in signaling."},"narrative":{"mechanistic_narrative":"SNX20 (SLIC-1) is an endosomal sorting nexin that controls the subcellular trafficking of the leukocyte adhesion receptor PSGL-1 [PMID:18196517]. It binds directly to the cytoplasmic domain of PSGL-1 through a mapped interaction motif [PMID:18196517], and its Phox homology (PX) domain binds phosphoinositides to target the resulting PSGL-1/SNX20 complex to endosomes [PMID:18196517]. Loss of the murine homologue does not impair PSGL-1-dependent signaling or neutrophil adhesion, indicating that SNX20 acts in endosomal recycling/sorting of PSGL-1 rather than in outside-in signaling or leukocyte recruitment [PMID:18196517]. Beyond this PSGL-1 trafficking role, no further binding partners or mechanistic detail for SNX20 have been characterized in the available corpus [PMID:30072438].","teleology":[{"year":2008,"claim":"Establishing a physical partner for SNX20 defined its first molecular function: a yeast two-hybrid screen identified direct binding to the cytoplasmic domain of the adhesion receptor PSGL-1.","evidence":"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, and motif mapping","pmids":["18196517"],"confidence":"Medium","gaps":["Binding interface defined only by motif mapping, not by structure","Whether SNX20 binds other receptor tails was not tested"]},{"year":2008,"claim":"Localizing the complex addressed where SNX20 acts: its PX domain binds phosphoinositides and targets the PSGL-1/SNX20 complex to endosomes, placing SNX20 in the membrane sorting machinery.","evidence":"Colocalization imaging and subcellular fractionation","pmids":["18196517"],"confidence":"Medium","gaps":["Specific phosphoinositide species bound not resolved","No direct lipid-binding biochemistry reported"]},{"year":2008,"claim":"A knockout addressed whether SNX20 contributes to PSGL-1 signaling versus trafficking: loss of the murine homologue left PSGL-1-dependent signaling and neutrophil adhesion intact, confining SNX20's role to endosomal sorting rather than leukocyte recruitment.","evidence":"Knockout mouse with neutrophil adhesion and signaling assays","pmids":["18196517"],"confidence":"Medium","gaps":["Direct measurement of PSGL-1 endosomal cycling kinetics not shown","Possible redundancy with related sorting nexins not assessed"]},{"year":2018,"claim":"Domain analysis placed SNX20 in the SNX-PXB family of predicted endosome-associated scaffolds, but no SNX20-specific interactome was generated.","evidence":"Quantitative proteomics on SNX21 with domain-based classification of SNX20","pmids":["30072438"],"confidence":"Low","gaps":["No direct experiment performed on SNX20 in this study","SNX20 binding partners beyond PSGL-1 remain unidentified","Scaffold function is predicted, not demonstrated"]},{"year":null,"claim":"Whether SNX20 has cargoes or functions beyond PSGL-1, and the molecular consequences of its endosomal sorting activity, remain undefined.","evidence":"No further direct functional characterization in the available corpus","pmids":[],"confidence":"Low","gaps":["No SNX20-specific interactome","No structural model of the PX or PXB domains","Functional significance of PSGL-1 recycling not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["SELPLG"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z614","full_name":"Sorting nexin-20","aliases":["Selectin ligand-interactor cytoplasmic 1","SLIC-1"],"length_aa":316,"mass_kda":36.2,"function":"May play a role in cellular vesicle trafficking. Has been proposed to function as a sorting protein that targets SELPLG into endosomes, but has no effect on SELPLG internalization from the cell surface, or on SELPLG-mediated cell-cell adhesion","subcellular_location":"Early endosome membrane; Cell membrane; Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q7Z614/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SNX20","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SNX20","total_profiled":1310},"omim":[{"mim_id":"619200","title":"SORTING NEXIN FAMILY, MEMBER 21; SNX21","url":"https://www.omim.org/entry/619200"},{"mim_id":"613281","title":"SORTING NEXIN 20; SNX20","url":"https://www.omim.org/entry/613281"},{"mim_id":"600738","title":"SELECTIN P LIGAND; SELPLG","url":"https://www.omim.org/entry/600738"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":14.7},{"tissue":"lymphoid tissue","ntpm":30.9}],"url":"https://www.proteinatlas.org/search/SNX20"},"hgnc":{"alias_symbol":["SLIC-1","SLIC1"],"prev_symbol":[]},"alphafold":{"accession":"Q7Z614","domains":[{"cath_id":"3.30.1520.10","chopping":"72-177","consensus_level":"medium","plddt":91.5207,"start":72,"end":177},{"cath_id":"1.25.40","chopping":"202-316","consensus_level":"medium","plddt":92.6738,"start":202,"end":316}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z614","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z614-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z614-F1-predicted_aligned_error_v6.png","plddt_mean":83.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SNX20","jax_strain_url":"https://www.jax.org/strain/search?query=SNX20"},"sequence":{"accession":"Q7Z614","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z614.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z614/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z614"}},"corpus_meta":[{"pmid":"18196517","id":"PMC_18196517","title":"SLIC-1/sorting nexin 20: a novel sorting nexin that directs subcellular distribution of PSGL-1.","date":"2008","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18196517","citation_count":22,"is_preprint":false},{"pmid":"33116590","id":"PMC_33116590","title":"Increased SNX20 and PD-L1 Levels Can Predict the Clinical Response to PD-1 Inhibitors in Lung Adenocarcinoma.","date":"2020","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33116590","citation_count":8,"is_preprint":false},{"pmid":"33358908","id":"PMC_33358908","title":"The molecular basis of gender disparities in smoking lung cancer patients.","date":"2020","source":"Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33358908","citation_count":8,"is_preprint":false},{"pmid":"30072438","id":"PMC_30072438","title":"Sorting nexin-21 is a scaffold for the endosomal recruitment of huntingtin.","date":"2018","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/30072438","citation_count":8,"is_preprint":false},{"pmid":"35747917","id":"PMC_35747917","title":"[The Expression of RTN1 in Lung Adenocarcinoma and 
Its Effect on Immune Microenvironment].","date":"2022","source":"Zhongguo fei ai za zhi = Chinese journal of lung cancer","url":"https://pubmed.ncbi.nlm.nih.gov/35747917","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5277,"output_tokens":932,"usd":0.014906,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7390,"output_tokens":1636,"usd":0.038925,"stage2_stop_reason":"end_turn"},"total_usd":0.053831,"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\": 2008,\n      \"finding\": \"SLIC-1/SNX20 directly interacts with the cytoplasmic domain of PSGL-1, as identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation and motif mapping.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, motif mapping\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with motif mapping, single lab, two orthogonal methods\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"SLIC-1/SNX20 contains a Phox homology (PX) domain that binds phosphoinositides and targets the PSGL-1/SLIC-1 complex to endosomes, as demonstrated by colocalization experiments.\",\n      \"method\": \"Colocalization experiments, subcellular fractionation/imaging\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — colocalization established endosomal targeting, single lab but supported by known PX-domain phosphoinositide binding function and motif mapping\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Deficiency of the murine homologue of SLIC-1/SNX20 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1, indicating that SNX20 functions as a sorting molecule cycling PSGL-1 into endosomes without impacting leukocyte recruitment.\",\n      \"method\": \"Knockout mouse model, neutrophil adhesion assays, signaling assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in vivo with defined cellular phenotype readouts, single lab\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SNX20 and SNX21 are classified as SNX-PXB proteins based on the presence of a PX-associated B (PXB) domain, predicted to function as endosome-associated scaffolds; this paper established the SNX21 interactome but did not directly characterize SNX20 binding partners.\",\n      \"method\": \"Unbiased quantitative proteomics (for SNX21); classification of SNX20 as SNX-PXB protein by domain analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — SNX20 classification is domain-prediction based; no direct experiment performed on SNX20 in this paper\",\n      \"pmids\": [\"30072438\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNX20 (SLIC-1) is an endosomal sorting nexin that uses its PX domain to bind phosphoinositides and target the PSGL-1/SNX20 complex to endosomes; it directly interacts with the cytoplasmic domain of PSGL-1 but loss of SNX20 does not affect PSGL-1-dependent signaling or neutrophil adhesion, indicating its role is confined to endosomal recycling/sorting of PSGL-1 rather than outside-in signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SNX20 (SLIC-1) is an endosomal sorting nexin that controls the subcellular trafficking of the leukocyte adhesion receptor PSGL-1 [#0, #1]. It binds directly to the cytoplasmic domain of PSGL-1 through a mapped interaction motif [#0], and its Phox homology (PX) domain binds phosphoinositides to target the resulting PSGL-1/SNX20 complex to endosomes [#1]. Loss of the murine homologue does not impair PSGL-1-dependent signaling or neutrophil adhesion, indicating that SNX20 acts in endosomal recycling/sorting of PSGL-1 rather than in outside-in signaling or leukocyte recruitment [#2]. Beyond this PSGL-1 trafficking role, no further binding partners or mechanistic detail for SNX20 have been characterized in the available corpus [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Establishing a physical partner for SNX20 defined its first molecular function: a yeast two-hybrid screen identified direct binding to the cytoplasmic domain of the adhesion receptor PSGL-1.\",\n      \"evidence\": \"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, and motif mapping\",\n      \"pmids\": [\"18196517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding interface defined only by motif mapping, not by structure\",\n        \"Whether SNX20 binds other receptor tails was not tested\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Localizing the complex addressed where SNX20 acts: its PX domain binds phosphoinositides and targets the PSGL-1/SNX20 complex to endosomes, placing SNX20 in the membrane sorting machinery.\",\n      \"evidence\": \"Colocalization imaging and subcellular fractionation\",\n      \"pmids\": [\"18196517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific phosphoinositide species bound not resolved\",\n        \"No direct lipid-binding biochemistry reported\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"A knockout addressed whether SNX20 contributes to PSGL-1 signaling versus trafficking: loss of the murine homologue left PSGL-1-dependent signaling and neutrophil adhesion intact, confining SNX20's role to endosomal sorting rather than leukocyte recruitment.\",\n      \"evidence\": \"Knockout mouse with neutrophil adhesion and signaling assays\",\n      \"pmids\": [\"18196517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct measurement of PSGL-1 endosomal cycling kinetics not shown\",\n        \"Possible redundancy with related sorting nexins not assessed\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Domain analysis placed SNX20 in the SNX-PXB family of predicted endosome-associated scaffolds, but no SNX20-specific interactome was generated.\",\n      \"evidence\": \"Quantitative proteomics on SNX21 with domain-based classification of SNX20\",\n      \"pmids\": [\"30072438\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct experiment performed on SNX20 in this study\",\n        \"SNX20 binding partners beyond PSGL-1 remain unidentified\",\n        \"Scaffold function is predicted, not demonstrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether SNX20 has cargoes or functions beyond PSGL-1, and the molecular consequences of its endosomal sorting activity, remain undefined.\",\n      \"evidence\": \"No further direct functional characterization in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No SNX20-specific interactome\",\n        \"No structural model of the PX or PXB domains\",\n        \"Functional significance of PSGL-1 recycling not established\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SELPLG\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":3,"faith_pct":66.66666666666667}}