{"gene":"CHIC2","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":1999,"finding":"CHIC2 (BTL) fuses with ETV6 in acute myeloid leukemia with t(4;12)(q11-q12;p13), generating a BTL-ETV6 fusion transcript (but not the reciprocal ETV6-BTL transcript), in which both the complete helix-loop-helix (HLH) and ETS DNA-binding domains of ETV6 are retained in the chimeric protein, which is transcribed from the BTL promoter.","method":"RT-PCR detection of fusion transcripts, molecular cloning and characterization of the fusion gene structure in 4 AML patient samples","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RT-PCR across multiple patient cases with domain structure characterization, single lab","pmids":["10477709"],"is_preprint":false},{"year":2022,"finding":"CHIC2 forms a complex with the E3 ubiquitin ligase STUB1 that binds CSF2RB (the common β chain of IL-3, IL-5, and GM-CSF receptors) and promotes its ubiquitination and lysosomal degradation; genetic inactivation of either STUB1 or CHIC2 reduces CSF2RB ubiquitination and increases its protein stability, with effects most pronounced at low cytokine concentrations.","method":"Genetic screens in multiple cellular contexts, co-immunoprecipitation (complex formation), ubiquitination assays, protein stability measurements after STUB1/CHIC2 knockout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal complex formation, ubiquitination assays, genetic KO in multiple cellular contexts and cytokine conditions, multiple orthogonal methods in one study","pmids":["36108743"],"is_preprint":false},{"year":2025,"finding":"CHIC2 acts as an adapter protein within a STUB1-CHIC2 complex that negatively regulates cytokine receptor expression (including IL-27 receptor α) in CD8+ T cells; knockout of either Stub1 or Chic2 in CD8+ T cells enhances anti-tumor function across multiple murine tumor models, and IL-27 receptor α is identified as essential for the tumor growth control mediated by Stub1/Chic2 knockout.","method":"In vivo CRISPR screens in CD8+ T cells, genetic knockout experiments in murine tumor models, co-immunoprecipitation of STUB1-CHIC2 complex, cytokine receptor expression profiling in mouse and human CD8+ T cells","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo CRISPR screens, co-IP for complex, KO with defined cellular and tumor phenotype, validated in both mouse and human cells with multiple orthogonal approaches","pmids":["40796662"],"is_preprint":false},{"year":2003,"finding":"CHIC2 is located at chromosomal band 4q12, and its deletion serves as a surrogate marker for the FIP1L1-PDGFRA fusion (because CHIC2 lies between FIP1L1 and PDGFRA and is lost in the interstitial deletion that generates this fusion); the fusion occurs in an early hematopoietic progenitor as evidenced by its detection in enriched eosinophils, neutrophils, and mononuclear cells by both FISH and RT-PCR.","method":"Fluorescence in situ hybridization (FISH) for CHIC2 deletion, RT-PCR for FIP1L1-PDGFRA fusion transcript in enriched hematopoietic cell populations","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FISH and RT-PCR with multi-lineage cell fractionation establishing genomic context of CHIC2, single lab, limited patient numbers","pmids":["12842979"],"is_preprint":false}],"current_model":"CHIC2 functions as an adapter protein that forms a complex with the E3 ubiquitin ligase STUB1 to promote ubiquitination and lysosomal degradation of cytokine receptors (including CSF2RB and IL-27Rα), thereby negatively regulating cytokine receptor surface expression and CD8+ T cell anti-tumor function; additionally, CHIC2 is located at chromosome 4q12 between FIP1L1 and PDGFRA such that interstitial deletion fuses those kinase genes, and CHIC2 can itself be fused to ETV6 in AML generating a chimeric transcription factor."},"narrative":{"mechanistic_narrative":"CHIC2 functions as an adapter protein that pairs with the E3 ubiquitin ligase STUB1 to negatively regulate cytokine receptor surface levels by promoting their ubiquitination and degradation [PMID:36108743, PMID:40796662]. The STUB1–CHIC2 complex binds CSF2RB, the common β chain of the IL-3, IL-5, and GM-CSF receptors, driving its ubiquitination and lysosomal degradation; loss of either STUB1 or CHIC2 stabilizes CSF2RB, with the strongest effect at low cytokine concentrations [PMID:36108743]. In CD8+ T cells the same complex restrains expression of IL-27 receptor α, and knockout of CHIC2 (or STUB1) enhances anti-tumor function across murine tumor models in an IL-27Rα-dependent manner [PMID:40796662]. CHIC2 also has a recurrent role in hematologic malignancy: it lies at chromosome 4q12 between FIP1L1 and PDGFRA, such that the interstitial deletion fusing those kinase genes removes CHIC2, making CHIC2 loss a surrogate marker for the FIP1L1-PDGFRA fusion [PMID:12842979], and CHIC2 itself can fuse to ETV6 in AML with t(4;12), generating a chimeric transcript that retains the ETV6 HLH and ETS DNA-binding domains under the CHIC2 promoter [PMID:10477709].","teleology":[{"year":1999,"claim":"Established CHIC2 as a recurrent partner in leukemia-associated chromosomal rearrangement, defining its first disease relevance before any molecular function was known.","evidence":"RT-PCR detection and molecular cloning of the BTL(CHIC2)-ETV6 fusion in t(4;12) AML patient samples","pmids":["10477709"],"confidence":"Medium","gaps":["Functional consequence of the chimeric protein not tested","Native CHIC2 protein function not addressed","Single lab, limited patient numbers"]},{"year":2003,"claim":"Positioned CHIC2 within the 4q12 genomic neighborhood, showing its deletion marks the FIP1L1-PDGFRA fusion and clarifying that CHIC2 loss is a bystander of an oncogenic kinase rearrangement.","evidence":"FISH for CHIC2 deletion and RT-PCR for FIP1L1-PDGFRA in fractionated hematopoietic cell populations","pmids":["12842979"],"confidence":"Medium","gaps":["Does not establish a causal role for CHIC2 loss itself","Molecular function of CHIC2 still undefined","Limited patient cohort"]},{"year":2022,"claim":"Defined the first biochemical function of CHIC2 as a STUB1-associated adapter that targets the cytokine receptor common β chain CSF2RB for ubiquitination and lysosomal degradation.","evidence":"Genetic screens, co-IP, ubiquitination assays, and protein stability measurements after STUB1/CHIC2 knockout in multiple cellular contexts","pmids":["36108743"],"confidence":"High","gaps":["Structural basis of CHIC2–STUB1–CSF2RB assembly not resolved","Whether CHIC2 confers substrate specificity vs. acting as scaffold unclear","Range of receptor substrates beyond CSF2RB not fully mapped"]},{"year":2025,"claim":"Extended the STUB1–CHIC2 mechanism to immune regulation, showing the complex restrains IL-27Rα on CD8+ T cells and that its loss enhances anti-tumor immunity.","evidence":"In vivo CRISPR screens, knockout in murine tumor models, co-IP, and receptor profiling in mouse and human CD8+ T cells","pmids":["40796662"],"confidence":"High","gaps":["Direct ubiquitination of IL-27Rα by the complex not biochemically demonstrated here","Mechanism of receptor selectivity across cell types unknown","Therapeutic targetability not established"]},{"year":null,"claim":"How CHIC2 selects its receptor substrates and is recruited to STUB1, and whether its leukemia-associated rearrangements perturb this adapter function, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the CHIC2–STUB1 complex","No defined CHIC2 substrate-recognition determinant","Link between CHIC2 fusion/deletion events and its adapter function untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1]}],"complexes":["STUB1-CHIC2 complex"],"partners":["STUB1","CSF2RB"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UKJ5","full_name":"Cysteine-rich hydrophobic domain-containing protein 2","aliases":["BrX-like translocated in leukemia"],"length_aa":165,"mass_kda":19.3,"function":"","subcellular_location":"Cell membrane; Cytoplasmic vesicle","url":"https://www.uniprot.org/uniprotkb/Q9UKJ5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CHIC2","classification":"Not Classified","n_dependent_lines":10,"n_total_lines":1208,"dependency_fraction":0.008278145695364239},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CHIC2","total_profiled":1310},"omim":[{"mim_id":"604332","title":"CYSTEINE-RICH HYDROPHOBIC DOMAIN PROTEIN 2; CHIC2","url":"https://www.omim.org/entry/604332"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Vesicles","reliability":"Enhanced"},{"location":"Plasma membrane","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CHIC2"},"hgnc":{"alias_symbol":["BTL"],"prev_symbol":[]},"alphafold":{"accession":"Q9UKJ5","domains":[{"cath_id":"-","chopping":"28-49_59-154","consensus_level":"high","plddt":89.4531,"start":28,"end":154}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKJ5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKJ5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UKJ5-F1-predicted_aligned_error_v6.png","plddt_mean":84.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CHIC2","jax_strain_url":"https://www.jax.org/strain/search?query=CHIC2"},"sequence":{"accession":"Q9UKJ5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UKJ5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UKJ5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UKJ5"}},"corpus_meta":[{"pmid":"12842979","id":"PMC_12842979","title":"CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.","date":"2003","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/12842979","citation_count":298,"is_preprint":false},{"pmid":"10477709","id":"PMC_10477709","title":"Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).","date":"1999","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/10477709","citation_count":69,"is_preprint":false},{"pmid":"10803852","id":"PMC_10803852","title":"BTL-II: a polymorphic locus with homology to the butyrophilin gene family, located at the border of the major histocompatibility complex class II and class III regions in human and mouse.","date":"2000","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/10803852","citation_count":59,"is_preprint":false},{"pmid":"24496629","id":"PMC_24496629","title":"Fascin links Btl/FGFR signalling to the actin cytoskeleton during Drosophila tracheal morphogenesis.","date":"2014","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/24496629","citation_count":26,"is_preprint":false},{"pmid":"18534036","id":"PMC_18534036","title":"Modulation of the pharmacological effects of enzymatically-active PLA2 by BTL-2, an isolectin isolated from the Bryothamnion triquetrum red alga.","date":"2008","source":"BMC biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/18534036","citation_count":14,"is_preprint":false},{"pmid":"23951330","id":"PMC_23951330","title":"Expansion and diversification of BTL ring-H2 ubiquitin ligases in angiosperms: putative Rabring7/BCA2 orthologs.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23951330","citation_count":13,"is_preprint":false},{"pmid":"40796662","id":"PMC_40796662","title":"A STUB1-CHIC2 complex inhibits CD8+ T cells to restrain tumor immunity.","date":"2025","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40796662","citation_count":9,"is_preprint":false},{"pmid":"19118897","id":"PMC_19118897","title":"Validation of a new three-color fluorescence in situ hybridization (FISH) method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations.","date":"2008","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/19118897","citation_count":8,"is_preprint":false},{"pmid":"36108743","id":"PMC_36108743","title":"A STUB1 ubiquitin ligase/CHIC2 protein complex negatively regulates the IL-3, IL-5, and GM-CSF cytokine receptor common β chain (CSF2RB) protein stability.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/36108743","citation_count":7,"is_preprint":false},{"pmid":"39037342","id":"PMC_39037342","title":"Acute myeloid leukemia with ETV6::CHIC2 fusion gene: 'Pitfalls' in diagnosis.","date":"2024","source":"Hematology (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/39037342","citation_count":3,"is_preprint":false},{"pmid":"29948614","id":"PMC_29948614","title":"Recent advances of Blood telomere length (BTL) shortening: A potential biomarker for development of cancer.","date":"2018","source":"Pathology oncology research : POR","url":"https://pubmed.ncbi.nlm.nih.gov/29948614","citation_count":3,"is_preprint":false},{"pmid":"34781094","id":"PMC_34781094","title":"Utilizing next-generation sequencing to characterize a case of acute myeloid leukemia with t(4;12)(q12;p13) in the absence of ETV6/CHIC2 and ETV6/PDGFRA gene fusions.","date":"2021","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/34781094","citation_count":2,"is_preprint":false},{"pmid":"18025566","id":"PMC_18025566","title":"Cell bound and extracellular glucose oxidases from Aspergillus niger BTL: evidence for a secondary glycosylation mechanism.","date":"2007","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/18025566","citation_count":2,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.22.629985","title":"Cell-associated viral community composition and its functional potential in a dimictic lake on the Canadian Shield","date":"2024-12-23","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.22.629985","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9255,"output_tokens":1277,"usd":0.02346,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7915,"output_tokens":1984,"usd":0.044588,"stage2_stop_reason":"end_turn"},"total_usd":0.068048,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"CHIC2 (BTL) fuses with ETV6 in acute myeloid leukemia with t(4;12)(q11-q12;p13), generating a BTL-ETV6 fusion transcript (but not the reciprocal ETV6-BTL transcript), in which both the complete helix-loop-helix (HLH) and ETS DNA-binding domains of ETV6 are retained in the chimeric protein, which is transcribed from the BTL promoter.\",\n      \"method\": \"RT-PCR detection of fusion transcripts, molecular cloning and characterization of the fusion gene structure in 4 AML patient samples\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RT-PCR across multiple patient cases with domain structure characterization, single lab\",\n      \"pmids\": [\"10477709\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CHIC2 forms a complex with the E3 ubiquitin ligase STUB1 that binds CSF2RB (the common β chain of IL-3, IL-5, and GM-CSF receptors) and promotes its ubiquitination and lysosomal degradation; genetic inactivation of either STUB1 or CHIC2 reduces CSF2RB ubiquitination and increases its protein stability, with effects most pronounced at low cytokine concentrations.\",\n      \"method\": \"Genetic screens in multiple cellular contexts, co-immunoprecipitation (complex formation), ubiquitination assays, protein stability measurements after STUB1/CHIC2 knockout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal complex formation, ubiquitination assays, genetic KO in multiple cellular contexts and cytokine conditions, multiple orthogonal methods in one study\",\n      \"pmids\": [\"36108743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CHIC2 acts as an adapter protein within a STUB1-CHIC2 complex that negatively regulates cytokine receptor expression (including IL-27 receptor α) in CD8+ T cells; knockout of either Stub1 or Chic2 in CD8+ T cells enhances anti-tumor function across multiple murine tumor models, and IL-27 receptor α is identified as essential for the tumor growth control mediated by Stub1/Chic2 knockout.\",\n      \"method\": \"In vivo CRISPR screens in CD8+ T cells, genetic knockout experiments in murine tumor models, co-immunoprecipitation of STUB1-CHIC2 complex, cytokine receptor expression profiling in mouse and human CD8+ T cells\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo CRISPR screens, co-IP for complex, KO with defined cellular and tumor phenotype, validated in both mouse and human cells with multiple orthogonal approaches\",\n      \"pmids\": [\"40796662\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"CHIC2 is located at chromosomal band 4q12, and its deletion serves as a surrogate marker for the FIP1L1-PDGFRA fusion (because CHIC2 lies between FIP1L1 and PDGFRA and is lost in the interstitial deletion that generates this fusion); the fusion occurs in an early hematopoietic progenitor as evidenced by its detection in enriched eosinophils, neutrophils, and mononuclear cells by both FISH and RT-PCR.\",\n      \"method\": \"Fluorescence in situ hybridization (FISH) for CHIC2 deletion, RT-PCR for FIP1L1-PDGFRA fusion transcript in enriched hematopoietic cell populations\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FISH and RT-PCR with multi-lineage cell fractionation establishing genomic context of CHIC2, single lab, limited patient numbers\",\n      \"pmids\": [\"12842979\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CHIC2 functions as an adapter protein that forms a complex with the E3 ubiquitin ligase STUB1 to promote ubiquitination and lysosomal degradation of cytokine receptors (including CSF2RB and IL-27Rα), thereby negatively regulating cytokine receptor surface expression and CD8+ T cell anti-tumor function; additionally, CHIC2 is located at chromosome 4q12 between FIP1L1 and PDGFRA such that interstitial deletion fuses those kinase genes, and CHIC2 can itself be fused to ETV6 in AML generating a chimeric transcription factor.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CHIC2 functions as an adapter protein that pairs with the E3 ubiquitin ligase STUB1 to negatively regulate cytokine receptor surface levels by promoting their ubiquitination and degradation [#1, #2]. The STUB1–CHIC2 complex binds CSF2RB, the common β chain of the IL-3, IL-5, and GM-CSF receptors, driving its ubiquitination and lysosomal degradation; loss of either STUB1 or CHIC2 stabilizes CSF2RB, with the strongest effect at low cytokine concentrations [#1]. In CD8+ T cells the same complex restrains expression of IL-27 receptor α, and knockout of CHIC2 (or STUB1) enhances anti-tumor function across murine tumor models in an IL-27Rα-dependent manner [#2]. CHIC2 also has a recurrent role in hematologic malignancy: it lies at chromosome 4q12 between FIP1L1 and PDGFRA, such that the interstitial deletion fusing those kinase genes removes CHIC2, making CHIC2 loss a surrogate marker for the FIP1L1-PDGFRA fusion [#3], and CHIC2 itself can fuse to ETV6 in AML with t(4;12), generating a chimeric transcript that retains the ETV6 HLH and ETS DNA-binding domains under the CHIC2 promoter [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established CHIC2 as a recurrent partner in leukemia-associated chromosomal rearrangement, defining its first disease relevance before any molecular function was known.\",\n      \"evidence\": \"RT-PCR detection and molecular cloning of the BTL(CHIC2)-ETV6 fusion in t(4;12) AML patient samples\",\n      \"pmids\": [\"10477709\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the chimeric protein not tested\",\n        \"Native CHIC2 protein function not addressed\",\n        \"Single lab, limited patient numbers\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Positioned CHIC2 within the 4q12 genomic neighborhood, showing its deletion marks the FIP1L1-PDGFRA fusion and clarifying that CHIC2 loss is a bystander of an oncogenic kinase rearrangement.\",\n      \"evidence\": \"FISH for CHIC2 deletion and RT-PCR for FIP1L1-PDGFRA in fractionated hematopoietic cell populations\",\n      \"pmids\": [\"12842979\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not establish a causal role for CHIC2 loss itself\",\n        \"Molecular function of CHIC2 still undefined\",\n        \"Limited patient cohort\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined the first biochemical function of CHIC2 as a STUB1-associated adapter that targets the cytokine receptor common β chain CSF2RB for ubiquitination and lysosomal degradation.\",\n      \"evidence\": \"Genetic screens, co-IP, ubiquitination assays, and protein stability measurements after STUB1/CHIC2 knockout in multiple cellular contexts\",\n      \"pmids\": [\"36108743\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of CHIC2–STUB1–CSF2RB assembly not resolved\",\n        \"Whether CHIC2 confers substrate specificity vs. acting as scaffold unclear\",\n        \"Range of receptor substrates beyond CSF2RB not fully mapped\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended the STUB1–CHIC2 mechanism to immune regulation, showing the complex restrains IL-27Rα on CD8+ T cells and that its loss enhances anti-tumor immunity.\",\n      \"evidence\": \"In vivo CRISPR screens, knockout in murine tumor models, co-IP, and receptor profiling in mouse and human CD8+ T cells\",\n      \"pmids\": [\"40796662\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct ubiquitination of IL-27Rα by the complex not biochemically demonstrated here\",\n        \"Mechanism of receptor selectivity across cell types unknown\",\n        \"Therapeutic targetability not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CHIC2 selects its receptor substrates and is recruited to STUB1, and whether its leukemia-associated rearrangements perturb this adapter function, remain unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the CHIC2–STUB1 complex\",\n        \"No defined CHIC2 substrate-recognition determinant\",\n        \"Link between CHIC2 fusion/deletion events and its adapter function untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"STUB1-CHIC2 complex\"],\n    \"partners\": [\"STUB1\", \"CSF2RB\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}