{"gene":"SLX9","run_date":"2026-06-10T07:46:35","timeline":{"discoveries":[{"year":2015,"finding":"Slx9 is a novel RanGTP-binding protein that facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a trimeric complex that directly loads Crm1 via a non-canonical stepwise mechanism. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export, establishing Slx9 as a scaffold that optimally presents RanGTP and the NES to Crm1 to trigger 40S pre-ribosome nuclear export.","method":"In vitro binding assays, mutational analysis, nuclear export assays, co-immunoprecipitation","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of trimeric complex plus mutagenesis with defined functional readout (export inhibition) in single rigorous study","pmids":["25895666"],"is_preprint":false},{"year":2010,"finding":"C21orf70 (SLX9/FAM207A) was identified as a novel component of human pre-40S ribosomal particles by tandem affinity purification of pre-40S assemblies in human somatic cells.","method":"Tandem affinity purification (TAP) of pre-40S ribosomal particles combined with mass spectrometry","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — TAP-MS identification of pre-40S association in a single study, no functional follow-up on this specific protein","pmids":["21097556"],"is_preprint":false},{"year":2006,"finding":"Yeast Slx9p (Ygr081cp) is associated with 35S, 23S, and 20S pre-rRNA and U3 snoRNA (making it a bona fide pre-ribosome component), and deletion of SLX9 causes accumulation of mutually exclusive 21S and 27SA2 pre-rRNA intermediates, indicating a role in ITS1 processing events that separate the 66S and 43S pre-ribosomal particles. Synthetic lethality of slx9Δ with Rrp5p mutations blocking cleavage at site A2 or A3 places Slx9p genetically at ITS1 processing.","method":"Co-immunoprecipitation (pre-rRNA and U3 snoRNA association), Northern blotting of pre-rRNA processing intermediates, genetic epistasis (synthetic lethality with rrp5 mutants)","journal":"RNA (New York, N.Y.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP for pre-rRNA association plus epistasis analysis, single lab but two orthogonal methods","pmids":["17018574"],"is_preprint":false},{"year":2019,"finding":"In yeast, Slx9 binds G-quadruplex (G4) DNA structures in vitro, identified in a yeast one-hybrid screen. Genome-wide ChIP-seq shows only insignificant binding to G4 regions under normal conditions, but Slx9 binding to G4 structures is significantly increased in the absence of the RecQ helicase Sgs1, suggesting Slx9 recognizes and protects stabilized G4 structures when they are not unwound.","method":"Yeast one-hybrid screen, in vitro G4 binding assay, genome-wide ChIP-seq in wild-type and sgs1Δ cells","journal":"Molecules (Basel, Switzerland)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro binding confirmed plus ChIP-seq functional context, single lab with two orthogonal methods","pmids":["31067825"],"is_preprint":false},{"year":2019,"finding":"In yeast, formation of the S0-cluster of ribosomal proteins around rpS0 (uS2) on late SSU precursors is required for efficient release of the nuclear export factors Rrp12 and Slx9 from SSU precursors, placing Slx9 release downstream of S0-cluster assembly as part of an r-protein assembly checkpoint during late SSU maturation.","method":"Semi-quantitative proteomics of Rio2-associated SSU precursors combined with complementary biochemical fractionation in S. cerevisiae r-protein mutants","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — quantitative proteomics plus biochemical validation, single lab, mechanistic placement inferred from mutant comparison","pmids":["30653518"],"is_preprint":false},{"year":2021,"finding":"FAM207A (SLX9) associates with proteins involved in ribosome biosynthesis and localizes to the nucleolus, as detected by proximity-dependent biotinylation (BioID) in human cells.","method":"BioID proximity-dependent biotinylation, subcellular localization imaging","journal":"PLoS genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — BioID proximity association and localization data from a single screen with limited mechanistic follow-up on FAM207A specifically","pmids":["34780483"],"is_preprint":false}],"current_model":"SLX9/FAM207A (C21orf70) encodes a RanGTP-binding scaffold protein that associates with pre-40S ribosomal particles in the nucleus, where it forms a trimeric complex with Rio2 and RanGTP to recruit Crm1 and drive nuclear export of the 40S pre-ribosome via a non-canonical, stepwise assembly mechanism; in yeast, the ortholog Slx9p additionally facilitates ITS1 pre-rRNA processing and is released from late SSU precursors upon completion of S0-cluster assembly, and it can also bind G-quadruplex DNA structures under conditions where the RecQ helicase Sgs1 is absent."},"narrative":{"mechanistic_narrative":"SLX9 (FAM207A/C21orf70) is a pre-40S ribosomal particle component that functions in small subunit (SSU) maturation and nuclear export [PMID:21097556, PMID:17018574]. It acts as a RanGTP-binding scaffold that forms a trimeric complex with the pre-40S-associated NES adaptor Rio2 and RanGTP, thereby loading the exportin Crm1 through a non-canonical, stepwise mechanism to drive 40S pre-ribosome nuclear export; a mutation that disrupts Crm1-export complex assembly blocks this export [PMID:25895666]. In yeast, Slx9p additionally associates with 35S, 23S, and 20S pre-rRNA and U3 snoRNA and is required for ITS1 processing events that separate the large- and small-subunit pre-ribosomal particles [PMID:17018574], and its release from late SSU precursors is gated by assembly of the rpS0 (uS2) S0-cluster as part of an r-protein assembly checkpoint [PMID:30653518]. Beyond its ribosomal role, yeast Slx9 binds G-quadruplex DNA in vitro and accumulates at G4 structures when the RecQ helicase Sgs1 is absent [PMID:31067825].","teleology":[{"year":2006,"claim":"Established Slx9 as a bona fide pre-ribosome component and placed it functionally at ITS1 processing, answering what cellular process the previously uncharacterized protein participates in.","evidence":"Co-IP of pre-rRNA/U3 snoRNA, Northern blotting of processing intermediates, and synthetic lethality with rrp5 mutants in yeast","pmids":["17018574"],"confidence":"Medium","gaps":["Does not define the direct molecular activity of Slx9 in cleavage","Conservation of the processing role in human cells not addressed","No structural or interaction detail with the processing machinery"]},{"year":2010,"claim":"Showed the human ortholog C21orf70/SLX9 is a constituent of human pre-40S particles, establishing conservation of the ribosomal association in human cells.","evidence":"Tandem affinity purification of pre-40S particles with mass spectrometry in human somatic cells","pmids":["21097556"],"confidence":"Medium","gaps":["No functional follow-up on the human protein specifically","Does not establish a mechanism within human pre-40S maturation"]},{"year":2015,"claim":"Defined the molecular mechanism by which Slx9 promotes 40S export, resolving how the NES adaptor Rio2 is coupled to Crm1.","evidence":"In vitro reconstitution of a Slx9-Rio2-RanGTP trimeric complex, mutational analysis, and nuclear export assays","pmids":["25895666"],"confidence":"High","gaps":["Structural basis of the scaffold interaction not determined","Whether the human ortholog uses the identical Crm1-loading mechanism not tested","Timing of Slx9 action relative to other export factors unresolved"]},{"year":2019,"claim":"Placed Slx9 release within a defined r-protein assembly checkpoint, clarifying when Slx9 leaves the maturing SSU particle.","evidence":"Semi-quantitative proteomics of Rio2-associated SSU precursors plus biochemical fractionation in yeast r-protein mutants","pmids":["30653518"],"confidence":"Medium","gaps":["Mechanistic trigger linking S0-cluster assembly to Slx9 release not defined","Release inferred from mutant comparison rather than direct kinetics"]},{"year":2019,"claim":"Revealed a non-ribosomal activity of Slx9 as a G-quadruplex DNA binder that engages stabilized G4 structures when Sgs1 is absent.","evidence":"Yeast one-hybrid screen, in vitro G4 binding assay, and genome-wide ChIP-seq in wild-type and sgs1Δ cells","pmids":["31067825"],"confidence":"Medium","gaps":["Biological consequence of G4 binding (protection vs. processing) not functionally demonstrated","Relationship between the ribosomal and G4-binding roles unknown","Whether human SLX9 binds G4 DNA not tested"]},{"year":2021,"claim":"Reinforced the ribosome-biogenesis association and nucleolar localization of the human protein via proximity labeling.","evidence":"BioID proximity-dependent biotinylation and subcellular localization imaging in human cells","pmids":["34780483"],"confidence":"Low","gaps":["BioID proximity does not establish direct interactions or mechanism for FAM207A specifically","Single screen with limited functional follow-up"]},{"year":null,"claim":"Whether the human protein recapitulates the yeast ITS1-processing and G4-binding functions, and the structural basis of its Rio2/RanGTP/Crm1 scaffolding, remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of the Slx9-Rio2-RanGTP-Crm1 assembly","Human-specific functional dissection of SLX9 lacking","Functional significance of G4 binding in vivo undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[5]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0]}],"complexes":["pre-40S ribosomal particle"],"partners":["RIO2","RAN","CRM1","RRP5","RRP12"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NSI2","full_name":"Ribosome biogenesis protein SLX9 homolog","aliases":[],"length_aa":230,"mass_kda":25.5,"function":"May be involved in ribosome biogenesis","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9NSI2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/SLX9","classification":"Common Essential","n_dependent_lines":558,"n_total_lines":1208,"dependency_fraction":0.46192052980132453},"opencell":{"profiled":true,"resolved_as":"FAM207A","ensg_id":"ENSG00000160256","cell_line_id":"CID002011","localizations":[{"compartment":"nucleolus_gc","grade":3},{"compartment":"nucleoplasm","grade":2},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"BYSL","stoichiometry":4.0},{"gene":"TSR1","stoichiometry":4.0},{"gene":"RPS11","stoichiometry":0.2},{"gene":"TNPO1","stoichiometry":0.2},{"gene":"NOP14","stoichiometry":0.2},{"gene":"CSNK1E","stoichiometry":0.2},{"gene":"RRP12","stoichiometry":0.2},{"gene":"PARN","stoichiometry":0.2},{"gene":"WBSCR22","stoichiometry":0.2},{"gene":"PNO1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID002011","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoli","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/SLX9"},"hgnc":{"alias_symbol":["PRED56"],"prev_symbol":["C21orf70","FAM207A"]},"alphafold":{"accession":"Q9NSI2","domains":[{"cath_id":"-","chopping":"185-229","consensus_level":"high","plddt":92.0064,"start":185,"end":229},{"cath_id":"1.20.5","chopping":"105-156","consensus_level":"medium","plddt":87.9035,"start":105,"end":156}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NSI2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NSI2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NSI2-F1-predicted_aligned_error_v6.png","plddt_mean":71.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLX9","jax_strain_url":"https://www.jax.org/strain/search?query=SLX9"},"sequence":{"accession":"Q9NSI2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NSI2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NSI2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NSI2"}},"corpus_meta":[{"pmid":"21097556","id":"PMC_21097556","title":"Tandem affinity purification combined with inducible shRNA expression as a tool to study the maturation of macromolecular assemblies.","date":"2010","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/21097556","citation_count":41,"is_preprint":false},{"pmid":"25895666","id":"PMC_25895666","title":"A non-canonical mechanism for Crm1-export cargo complex assembly.","date":"2015","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/25895666","citation_count":35,"is_preprint":false},{"pmid":"11707072","id":"PMC_11707072","title":"From PREDs and open reading frames to cDNA isolation: revisiting the human chromosome 21 transcription map.","date":"2001","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/11707072","citation_count":34,"is_preprint":false},{"pmid":"17018574","id":"PMC_17018574","title":"Slx9p facilitates efficient ITS1 processing of pre-rRNA in Saccharomyces cerevisiae.","date":"2006","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/17018574","citation_count":22,"is_preprint":false},{"pmid":"34780483","id":"PMC_34780483","title":"ATRX proximal protein associations boast roles beyond histone deposition.","date":"2021","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34780483","citation_count":19,"is_preprint":false},{"pmid":"31067825","id":"PMC_31067825","title":"A Novel G-Quadruplex Binding Protein in Yeast-Slx9.","date":"2019","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31067825","citation_count":15,"is_preprint":false},{"pmid":"30653518","id":"PMC_30653518","title":"Impact of two neighbouring ribosomal protein clusters on biogenesis factor binding and assembly of yeast late small ribosomal subunit precursors.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30653518","citation_count":11,"is_preprint":false},{"pmid":"20551975","id":"PMC_20551975","title":"A new plant sex-linked gene with high sequence diversity and possible introgression of the X copy.","date":"2010","source":"Heredity","url":"https://pubmed.ncbi.nlm.nih.gov/20551975","citation_count":9,"is_preprint":false},{"pmid":"40259152","id":"PMC_40259152","title":"FAM207A acts as a novel and potential biomarker in lung adenocarcinoma and shapes the immunesuppressive tumor microenvironment.","date":"2025","source":"Clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40259152","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6168,"output_tokens":1688,"usd":0.021912,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8456,"output_tokens":2291,"usd":0.049778,"stage2_stop_reason":"end_turn"},"total_usd":0.07169,"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\": 2015,\n      \"finding\": \"Slx9 is a novel RanGTP-binding protein that facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a trimeric complex that directly loads Crm1 via a non-canonical stepwise mechanism. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export, establishing Slx9 as a scaffold that optimally presents RanGTP and the NES to Crm1 to trigger 40S pre-ribosome nuclear export.\",\n      \"method\": \"In vitro binding assays, mutational analysis, nuclear export assays, co-immunoprecipitation\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of trimeric complex plus mutagenesis with defined functional readout (export inhibition) in single rigorous study\",\n      \"pmids\": [\"25895666\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"C21orf70 (SLX9/FAM207A) was identified as a novel component of human pre-40S ribosomal particles by tandem affinity purification of pre-40S assemblies in human somatic cells.\",\n      \"method\": \"Tandem affinity purification (TAP) of pre-40S ribosomal particles combined with mass spectrometry\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — TAP-MS identification of pre-40S association in a single study, no functional follow-up on this specific protein\",\n      \"pmids\": [\"21097556\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Yeast Slx9p (Ygr081cp) is associated with 35S, 23S, and 20S pre-rRNA and U3 snoRNA (making it a bona fide pre-ribosome component), and deletion of SLX9 causes accumulation of mutually exclusive 21S and 27SA2 pre-rRNA intermediates, indicating a role in ITS1 processing events that separate the 66S and 43S pre-ribosomal particles. Synthetic lethality of slx9Δ with Rrp5p mutations blocking cleavage at site A2 or A3 places Slx9p genetically at ITS1 processing.\",\n      \"method\": \"Co-immunoprecipitation (pre-rRNA and U3 snoRNA association), Northern blotting of pre-rRNA processing intermediates, genetic epistasis (synthetic lethality with rrp5 mutants)\",\n      \"journal\": \"RNA (New York, N.Y.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP for pre-rRNA association plus epistasis analysis, single lab but two orthogonal methods\",\n      \"pmids\": [\"17018574\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In yeast, Slx9 binds G-quadruplex (G4) DNA structures in vitro, identified in a yeast one-hybrid screen. Genome-wide ChIP-seq shows only insignificant binding to G4 regions under normal conditions, but Slx9 binding to G4 structures is significantly increased in the absence of the RecQ helicase Sgs1, suggesting Slx9 recognizes and protects stabilized G4 structures when they are not unwound.\",\n      \"method\": \"Yeast one-hybrid screen, in vitro G4 binding assay, genome-wide ChIP-seq in wild-type and sgs1Δ cells\",\n      \"journal\": \"Molecules (Basel, Switzerland)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro binding confirmed plus ChIP-seq functional context, single lab with two orthogonal methods\",\n      \"pmids\": [\"31067825\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In yeast, formation of the S0-cluster of ribosomal proteins around rpS0 (uS2) on late SSU precursors is required for efficient release of the nuclear export factors Rrp12 and Slx9 from SSU precursors, placing Slx9 release downstream of S0-cluster assembly as part of an r-protein assembly checkpoint during late SSU maturation.\",\n      \"method\": \"Semi-quantitative proteomics of Rio2-associated SSU precursors combined with complementary biochemical fractionation in S. cerevisiae r-protein mutants\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — quantitative proteomics plus biochemical validation, single lab, mechanistic placement inferred from mutant comparison\",\n      \"pmids\": [\"30653518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FAM207A (SLX9) associates with proteins involved in ribosome biosynthesis and localizes to the nucleolus, as detected by proximity-dependent biotinylation (BioID) in human cells.\",\n      \"method\": \"BioID proximity-dependent biotinylation, subcellular localization imaging\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — BioID proximity association and localization data from a single screen with limited mechanistic follow-up on FAM207A specifically\",\n      \"pmids\": [\"34780483\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"SLX9/FAM207A (C21orf70) encodes a RanGTP-binding scaffold protein that associates with pre-40S ribosomal particles in the nucleus, where it forms a trimeric complex with Rio2 and RanGTP to recruit Crm1 and drive nuclear export of the 40S pre-ribosome via a non-canonical, stepwise assembly mechanism; in yeast, the ortholog Slx9p additionally facilitates ITS1 pre-rRNA processing and is released from late SSU precursors upon completion of S0-cluster assembly, and it can also bind G-quadruplex DNA structures under conditions where the RecQ helicase Sgs1 is absent.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLX9 (FAM207A/C21orf70) is a pre-40S ribosomal particle component that functions in small subunit (SSU) maturation and nuclear export [#1, #2]. It acts as a RanGTP-binding scaffold that forms a trimeric complex with the pre-40S-associated NES adaptor Rio2 and RanGTP, thereby loading the exportin Crm1 through a non-canonical, stepwise mechanism to drive 40S pre-ribosome nuclear export; a mutation that disrupts Crm1-export complex assembly blocks this export [#0]. In yeast, Slx9p additionally associates with 35S, 23S, and 20S pre-rRNA and U3 snoRNA and is required for ITS1 processing events that separate the large- and small-subunit pre-ribosomal particles [#2], and its release from late SSU precursors is gated by assembly of the rpS0 (uS2) S0-cluster as part of an r-protein assembly checkpoint [#4]. Beyond its ribosomal role, yeast Slx9 binds G-quadruplex DNA in vitro and accumulates at G4 structures when the RecQ helicase Sgs1 is absent [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established Slx9 as a bona fide pre-ribosome component and placed it functionally at ITS1 processing, answering what cellular process the previously uncharacterized protein participates in.\",\n      \"evidence\": \"Co-IP of pre-rRNA/U3 snoRNA, Northern blotting of processing intermediates, and synthetic lethality with rrp5 mutants in yeast\",\n      \"pmids\": [\"17018574\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not define the direct molecular activity of Slx9 in cleavage\", \"Conservation of the processing role in human cells not addressed\", \"No structural or interaction detail with the processing machinery\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed the human ortholog C21orf70/SLX9 is a constituent of human pre-40S particles, establishing conservation of the ribosomal association in human cells.\",\n      \"evidence\": \"Tandem affinity purification of pre-40S particles with mass spectrometry in human somatic cells\",\n      \"pmids\": [\"21097556\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional follow-up on the human protein specifically\", \"Does not establish a mechanism within human pre-40S maturation\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined the molecular mechanism by which Slx9 promotes 40S export, resolving how the NES adaptor Rio2 is coupled to Crm1.\",\n      \"evidence\": \"In vitro reconstitution of a Slx9-Rio2-RanGTP trimeric complex, mutational analysis, and nuclear export assays\",\n      \"pmids\": [\"25895666\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the scaffold interaction not determined\", \"Whether the human ortholog uses the identical Crm1-loading mechanism not tested\", \"Timing of Slx9 action relative to other export factors unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed Slx9 release within a defined r-protein assembly checkpoint, clarifying when Slx9 leaves the maturing SSU particle.\",\n      \"evidence\": \"Semi-quantitative proteomics of Rio2-associated SSU precursors plus biochemical fractionation in yeast r-protein mutants\",\n      \"pmids\": [\"30653518\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic trigger linking S0-cluster assembly to Slx9 release not defined\", \"Release inferred from mutant comparison rather than direct kinetics\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a non-ribosomal activity of Slx9 as a G-quadruplex DNA binder that engages stabilized G4 structures when Sgs1 is absent.\",\n      \"evidence\": \"Yeast one-hybrid screen, in vitro G4 binding assay, and genome-wide ChIP-seq in wild-type and sgs1\\u0394 cells\",\n      \"pmids\": [\"31067825\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biological consequence of G4 binding (protection vs. processing) not functionally demonstrated\", \"Relationship between the ribosomal and G4-binding roles unknown\", \"Whether human SLX9 binds G4 DNA not tested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Reinforced the ribosome-biogenesis association and nucleolar localization of the human protein via proximity labeling.\",\n      \"evidence\": \"BioID proximity-dependent biotinylation and subcellular localization imaging in human cells\",\n      \"pmids\": [\"34780483\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"BioID proximity does not establish direct interactions or mechanism for FAM207A specifically\", \"Single screen with limited functional follow-up\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the human protein recapitulates the yeast ITS1-processing and G4-binding functions, and the structural basis of its Rio2/RanGTP/Crm1 scaffolding, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of the Slx9-Rio2-RanGTP-Crm1 assembly\", \"Human-specific functional dissection of SLX9 lacking\", \"Functional significance of G4 binding in vivo undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"pre-40S ribosomal particle\"],\n    \"partners\": [\"RIO2\", \"RAN\", \"CRM1\", \"RRP5\", \"RRP12\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}