{"gene":"SNX20","run_date":"2026-04-28T20:42:08","timeline":{"discoveries":[{"year":2008,"finding":"SNX20 (SLIC-1) 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 — reciprocal Co-IP with motif mapping, single lab","pmids":["18196517"],"is_preprint":false},{"year":2008,"finding":"SNX20 (SLIC-1) contains a Phox homology (PX) domain that binds phosphoinositides and targets the PSGL-1/SNX20 complex to endosomes, as demonstrated by colocalization experiments.","method":"Colocalization microscopy, PX domain functional analysis","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2-3 — direct localization experiment with functional consequence (endosomal targeting), single lab","pmids":["18196517"],"is_preprint":false},{"year":2008,"finding":"Deficiency of the murine homologue of SNX20 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1, indicating SNX20 functions as a sorting molecule cycling PSGL-1 into endosomes without impacting leukocyte recruitment.","method":"Loss-of-function mouse model, functional adhesion/signaling assays","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cellular phenotype, single lab","pmids":["18196517"],"is_preprint":false},{"year":2018,"finding":"SNX20 belongs to the SNX-PXB sub-family, possessing a PX-associated B (PXB) domain proposed to function as an endosome-associated scaffold for protein-protein interactions, consistent with the characterized role of its paralog SNX21.","method":"Bioinformatic domain analysis; functional context from SNX21 quantitative proteomics","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 4 — domain prediction supported by indirect analogy from SNX21 data, no direct SNX20 experiment","pmids":["30072438"],"is_preprint":false}],"current_model":"SNX20 is an endosomal sorting nexin that uses its PX domain to bind phosphoinositides and localize to endosomes, where it directly interacts (via its cytoplasmic-domain-binding activity) with PSGL-1 to cycle it into endosomes, but is dispensable for PSGL-1-dependent leukocyte adhesion and signaling."},"narrative":{"teleology":[{"year":2008,"claim":"Identification of SNX20 as a direct PSGL-1 cytoplasmic-domain interactor established that a sorting nexin participates in PSGL-1 trafficking, answering the question of how PSGL-1 is routed to endosomes.","evidence":"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, and motif mapping in human cells; PX-domain-dependent colocalization to endosomes; murine knockout with adhesion and signaling assays","pmids":["18196517"],"confidence":"Medium","gaps":["Single-lab study; independent replication in a second system is lacking","Structural basis of SNX20–PSGL-1 interaction is unresolved","Functional consequence of disrupted PSGL-1 endosomal sorting (e.g., surface turnover kinetics) was not quantified"]},{"year":2018,"claim":"Classification of SNX20 within the SNX-PXB sub-family suggested that its PXB domain serves as an endosome-associated scaffold, extending the mechanistic model from simple phosphoinositide binding to a platform for additional protein–protein interactions.","evidence":"Bioinformatic domain analysis and functional analogy drawn from quantitative proteomics of paralog SNX21","pmids":["30072438"],"confidence":"Low","gaps":["No direct experimental data on the SNX20 PXB domain; inference is based solely on SNX21 analogy","Interactors recruited by the PXB domain of SNX20 have not been identified","No structural or mutagenesis data for the SNX20 PXB domain"]},{"year":null,"claim":"It remains unknown whether SNX20 sorts additional cargo beyond PSGL-1, what the physiological consequence of disrupted PSGL-1 endosomal sorting is in vivo, and whether the PXB domain recruits specific effectors to endosomes.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unbiased cargo identification screen has been performed for SNX20","In vivo phenotype of SNX20 loss beyond leukocyte adhesion has not been examined","No structural model of SNX20 exists"]}],"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":[0,1]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,2]}],"pathway":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["SELPLG"],"other_free_text":[]},"mechanistic_narrative":"SNX20 is a sorting nexin of the SNX-PXB sub-family that directly binds the cytoplasmic domain of PSGL-1 and, through its phosphoinositide-binding PX domain, targets the SNX20–PSGL-1 complex to endosomes, thereby cycling PSGL-1 into the endosomal compartment [PMID:18196517]. Loss of SNX20 in a murine knockout model does not impair PSGL-1-dependent leukocyte adhesion or signaling, indicating that SNX20 functions specifically in PSGL-1 endosomal sorting rather than in adhesion or signal transduction [PMID:18196517]."},"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":"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":"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":"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":7,"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":4515,"output_tokens":823,"usd":0.012945},"stage2":{"model":"claude-opus-4-6","input_tokens":4021,"output_tokens":2017,"usd":0.105795},"total_usd":0.11874,"stage1_batch_id":"msgbatch_011rkcQdVV1RaFq9XhcG6df6","stage2_batch_id":"msgbatch_01RzgrJafdF4EWHhj5mNi6dh","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"SNX20 (SLIC-1) 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 — reciprocal Co-IP with motif mapping, single lab\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"SNX20 (SLIC-1) contains a Phox homology (PX) domain that binds phosphoinositides and targets the PSGL-1/SNX20 complex to endosomes, as demonstrated by colocalization experiments.\",\n      \"method\": \"Colocalization microscopy, PX domain functional analysis\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — direct localization experiment with functional consequence (endosomal targeting), single lab\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Deficiency of the murine homologue of SNX20 did not modulate PSGL-1-dependent signaling nor alter neutrophil adhesion through PSGL-1, indicating SNX20 functions as a sorting molecule cycling PSGL-1 into endosomes without impacting leukocyte recruitment.\",\n      \"method\": \"Loss-of-function mouse model, functional adhesion/signaling assays\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cellular phenotype, single lab\",\n      \"pmids\": [\"18196517\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SNX20 belongs to the SNX-PXB sub-family, possessing a PX-associated B (PXB) domain proposed to function as an endosome-associated scaffold for protein-protein interactions, consistent with the characterized role of its paralog SNX21.\",\n      \"method\": \"Bioinformatic domain analysis; functional context from SNX21 quantitative proteomics\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — domain prediction supported by indirect analogy from SNX21 data, no direct SNX20 experiment\",\n      \"pmids\": [\"30072438\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SNX20 is an endosomal sorting nexin that uses its PX domain to bind phosphoinositides and localize to endosomes, where it directly interacts (via its cytoplasmic-domain-binding activity) with PSGL-1 to cycle it into endosomes, but is dispensable for PSGL-1-dependent leukocyte adhesion and signaling.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SNX20 is a sorting nexin of the SNX-PXB sub-family that directly binds the cytoplasmic domain of PSGL-1 and, through its phosphoinositide-binding PX domain, targets the SNX20–PSGL-1 complex to endosomes, thereby cycling PSGL-1 into the endosomal compartment [PMID:18196517]. Loss of SNX20 in a murine knockout model does not impair PSGL-1-dependent leukocyte adhesion or signaling, indicating that SNX20 functions specifically in PSGL-1 endosomal sorting rather than in adhesion or signal transduction [PMID:18196517].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Identification of SNX20 as a direct PSGL-1 cytoplasmic-domain interactor established that a sorting nexin participates in PSGL-1 trafficking, answering the question of how PSGL-1 is routed to endosomes.\",\n      \"evidence\": \"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, and motif mapping in human cells; PX-domain-dependent colocalization to endosomes; murine knockout with adhesion and signaling assays\",\n      \"pmids\": [\"18196517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication in a second system is lacking\",\n        \"Structural basis of SNX20–PSGL-1 interaction is unresolved\",\n        \"Functional consequence of disrupted PSGL-1 endosomal sorting (e.g., surface turnover kinetics) was not quantified\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Classification of SNX20 within the SNX-PXB sub-family suggested that its PXB domain serves as an endosome-associated scaffold, extending the mechanistic model from simple phosphoinositide binding to a platform for additional protein–protein interactions.\",\n      \"evidence\": \"Bioinformatic domain analysis and functional analogy drawn from quantitative proteomics of paralog SNX21\",\n      \"pmids\": [\"30072438\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct experimental data on the SNX20 PXB domain; inference is based solely on SNX21 analogy\",\n        \"Interactors recruited by the PXB domain of SNX20 have not been identified\",\n        \"No structural or mutagenesis data for the SNX20 PXB domain\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SNX20 sorts additional cargo beyond PSGL-1, what the physiological consequence of disrupted PSGL-1 endosomal sorting is in vivo, and whether the PXB domain recruits specific effectors to endosomes.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unbiased cargo identification screen has been performed for SNX20\",\n        \"In vivo phenotype of SNX20 loss beyond leukocyte adhesion has not been examined\",\n        \"No structural model of SNX20 exists\"\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, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SELPLG\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to correct the pathway field — I used a GO term instead of a Reactome pathway ID. Let me fix that.\n\n```json\n{\n  \"mechanistic_narrative\": \"SNX20 is a sorting nexin of the SNX-PXB sub-family that directly binds the cytoplasmic domain of PSGL-1 and, through its phosphoinositide-binding PX domain, targets the SNX20–PSGL-1 complex to endosomes, thereby cycling PSGL-1 into the endosomal compartment [PMID:18196517]. Loss of SNX20 in a murine knockout model does not impair PSGL-1-dependent leukocyte adhesion or signaling, indicating that SNX20 functions specifically in PSGL-1 endosomal sorting rather than in adhesion or signal transduction [PMID:18196517].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Identification of SNX20 as a direct PSGL-1 cytoplasmic-domain interactor established that a sorting nexin participates in PSGL-1 trafficking, answering the question of how PSGL-1 is routed to endosomes.\",\n      \"evidence\": \"Yeast two-hybrid screen, reciprocal co-immunoprecipitation, and motif mapping in human cells; PX-domain-dependent colocalization to endosomes; murine knockout with adhesion and signaling assays\",\n      \"pmids\": [\"18196517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; independent replication in a second system is lacking\",\n        \"Structural basis of SNX20–PSGL-1 interaction is unresolved\",\n        \"Functional consequence of disrupted PSGL-1 endosomal sorting (e.g., surface turnover kinetics) was not quantified\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Classification of SNX20 within the SNX-PXB sub-family suggested that its PXB domain serves as an endosome-associated scaffold, extending the mechanistic model from simple phosphoinositide binding to a platform for additional protein–protein interactions.\",\n      \"evidence\": \"Bioinformatic domain analysis and functional analogy drawn from quantitative proteomics of paralog SNX21\",\n      \"pmids\": [\"30072438\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct experimental data on the SNX20 PXB domain; inference is based solely on SNX21 analogy\",\n        \"Interactors recruited by the PXB domain of SNX20 have not been identified\",\n        \"No structural or mutagenesis data for the SNX20 PXB domain\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether SNX20 sorts additional cargo beyond PSGL-1, what the physiological consequence of disrupted PSGL-1 endosomal sorting is in vivo, and whether the PXB domain recruits specific effectors to endosomes.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unbiased cargo identification screen has been performed for SNX20\",\n        \"In vivo phenotype of SNX20 loss beyond leukocyte adhesion has not been examined\",\n        \"No structural model of SNX20 exists\"\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, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 2]}\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}\n```"}