{"gene":"ANAPC7","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":2013,"finding":"ANAPC7 (APC7/AnapC7) was identified as a binding partner of both IL-17RA and IL-17RC cytoplasmic tails via yeast 2-hybrid screen. However, siRNA-mediated knockdown of AnapC7 exerted no detectable impact on IL-17 signaling. AnapC5, which associates with AnapC7, also bound IL-17RA and IL-17RC and functioned as a negative regulator of IL-17 signaling, and also associated with A20 (TNFAIP3).","method":"Yeast two-hybrid screen, siRNA knockdown, IL-17-induced gene expression assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — yeast 2-hybrid identification plus functional siRNA knockdown, but single lab and the ANAPC7 knockdown result was negative (no effect on IL-17 signaling)","pmids":["23922952"],"is_preprint":false},{"year":2024,"finding":"Genetic epistasis in mouse models and cell lines showed that co-depletion of ANAPC7 partially rescued KIF18A-depletion-induced mitotic arrest, while co-depletion of ANAPC5 exacerbated it. This establishes ANAPC7 as a functional component downstream or in opposition to KIF18A in mitotic progression, with ANAPC5 and ANAPC7 acting in opposing directions in the KIF18A-dependent mitotic pathway. A novel retroviral insertion in Anapc7 was identified that may influence its expression level and sensitivity to KIF18A loss.","method":"Genetic epistasis (double KD in cell lines), mouse genetic screen (strain background comparison), quantitative gene expression analysis","journal":"Scientific reports / bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in cell lines plus mouse genetic screen, replicated across preprint and peer-reviewed publication by same group, two orthogonal approaches","pmids":["39677807","40596695"],"is_preprint":false},{"year":2024,"finding":"C-FOS (AP-1 subunit) was shown by ChIP-seq to bind to the promoter of ANAPC7 and regulate its expression during mitotic clonal expansion in early adipogenesis of mesenchymal stem cells.","method":"Chromatin immunoprecipitation sequencing (ChIP-seq), gene expression analysis during adipogenesis","journal":"Journal of cellular biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, ChIP-seq identifies binding but functional validation of ANAPC7 regulation consequence is limited in the abstract","pmids":["38440920"],"is_preprint":false},{"year":2023,"finding":"ANAPC7 was experimentally verified as a PD-L1 interactor by co-immunoprecipitation in gastric cancer cells, and ANAPC7 expression was associated with immune escape when NK-92 cells were co-cultured with gastric cancer cells.","method":"Co-immunoprecipitation (Co-IP), NK cell co-culture experiment","journal":"Journal of cancer research and clinical oncology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP identifying interaction, co-culture functional assay without detailed mechanistic follow-up, single lab","pmids":["36592213"],"is_preprint":false}],"current_model":"ANAPC7 is a subunit of the anaphase-promoting complex (APC/C) that participates in mitotic progression; its depletion partially rescues KIF18A-loss-induced mitotic arrest (acting epistatically opposite to ANAPC5), it physically interacts with IL-17 receptor subunits (though its knockdown does not affect IL-17 signaling), its promoter is directly bound and regulated by C-FOS during mitotic clonal expansion in adipogenesis, and it co-immunoprecipitates with PD-L1 in gastric cancer cells with potential implications for immune evasion."},"narrative":{"mechanistic_narrative":"ANAPC7 functions as a component of the mitotic machinery, where genetic epistasis places it within the KIF18A-dependent pathway governing mitotic progression: co-depletion of ANAPC7 partially rescues the mitotic arrest caused by KIF18A loss, in direct opposition to ANAPC5, which exacerbates that arrest [PMID:39677807, PMID:40596695]. Beyond this mitotic role, ANAPC7 has been captured in physical-interaction contexts that have not been resolved into a defined mechanism—it binds the cytoplasmic tails of IL-17RA and IL-17RC in a yeast two-hybrid screen, but its knockdown produces no detectable effect on IL-17 signaling [PMID:23922952]. No catalytic activity, structural model, or substrate has been characterized for ANAPC7 in the available corpus.","teleology":[{"year":2013,"claim":"Testing whether ANAPC7 contributes to inflammatory receptor signaling, a yeast two-hybrid screen identified it as an IL-17 receptor binding partner, but functional knockdown showed it is dispensable for IL-17 signaling—placing its receptor association outside the IL-17 output pathway.","evidence":"Yeast two-hybrid screen with IL-17RA/IL-17RC cytoplasmic tails plus siRNA knockdown and IL-17-induced gene expression assays","pmids":["23922952"],"confidence":"Medium","gaps":["The biological consequence of the ANAPC7–IL-17R interaction is unresolved given the negative knockdown result","No reciprocal validation or structural mapping of the interaction interface","Functional contrast with ANAPC5 (a negative regulator binding the same receptors) leaves ANAPC7's role unexplained"]},{"year":2024,"claim":"To define ANAPC7's role in mitosis, genetic epistasis showed that depleting it partially relieves KIF18A-loss-induced mitotic arrest while depleting ANAPC5 worsens it, establishing the two subunits as functionally opposing within the KIF18A-dependent mitotic pathway.","evidence":"Double knockdown in cell lines and a mouse genetic screen comparing strain backgrounds, with quantitative expression analysis of an Anapc7 retroviral insertion","pmids":["39677807","40596695"],"confidence":"Medium","gaps":["The molecular basis for opposing ANAPC5 and ANAPC7 effects within the same complex is not defined","Whether the rescue reflects altered APC/C substrate targeting is untested","No direct substrate or biochemical readout connects ANAPC7 to the KIF18A axis"]},{"year":2024,"claim":"Addressing how ANAPC7 expression is controlled, ChIP-seq showed C-FOS binds its promoter during mitotic clonal expansion in early adipogenesis, linking ANAPC7 transcription to an AP-1-driven proliferative program.","evidence":"ChIP-seq and expression analysis during mesenchymal stem cell adipogenesis","pmids":["38440920"],"confidence":"Low","gaps":["Promoter binding does not establish a functional regulatory consequence for ANAPC7","No knockdown or reporter assay confirms C-FOS-driven ANAPC7 transcription","Downstream effect of ANAPC7 levels on adipogenesis is uncharacterized"]},{"year":2023,"claim":"Probing a potential role in tumor immune evasion, co-immunoprecipitation identified ANAPC7 as a PD-L1 interactor in gastric cancer cells, with its expression linked to NK-cell-mediated immune escape.","evidence":"Co-immunoprecipitation and NK-92 co-culture assay in gastric cancer cells","pmids":["36592213"],"confidence":"Low","gaps":["Single Co-IP without reciprocal validation of the PD-L1 interaction","Mechanism connecting ANAPC7 to PD-L1 stability or function is not defined","Causal contribution of ANAPC7 to immune escape is not established beyond correlation"]},{"year":null,"claim":"The biochemical activity of ANAPC7 within its complex—how it engages substrates and how it produces effects opposite to ANAPC5—remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No substrate or catalytic activity identified for ANAPC7","No structural model of how ANAPC7 and ANAPC5 contribute oppositely to mitotic progression","Mechanistic link between physical partners (IL-17R, PD-L1) and ANAPC7's mitotic function is unexplored"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1]}],"complexes":["APC/C"],"partners":["IL17RA","IL17RC","ANAPC5","CD274"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UJX3","full_name":"Anaphase-promoting complex subunit 7","aliases":["Cyclosome subunit 7"],"length_aa":565,"mass_kda":63.1,"function":"Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). APC7 is not required for the assembly of the APC/C complex, but has an enzyme-substrate adapter activity mediating the processive ubiquitination of specific substrates (PubMed:34942119). Involved in brain development through the specific ubiquitination and clearance of MKI67 from constitutive heterochromatin after neuronal progenitors exit mitosis (PubMed:34942119)","subcellular_location":"Cytoplasm, cytoskeleton; Nucleus; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q9UJX3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANAPC7","classification":"Not Classified","n_dependent_lines":71,"n_total_lines":1208,"dependency_fraction":0.058774834437086095},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ANAPC16","stoichiometry":10.0},{"gene":"ANAPC4","stoichiometry":10.0},{"gene":"CDC16","stoichiometry":10.0},{"gene":"CDC23","stoichiometry":10.0},{"gene":"CDC26","stoichiometry":10.0},{"gene":"CDC27","stoichiometry":10.0},{"gene":"ANAPC2","stoichiometry":0.2},{"gene":"H1F0","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"HMGA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ANAPC7","total_profiled":1310},"omim":[{"mim_id":"619699","title":"FERGUSON-BONNI NEURODEVELOPMENTAL SYNDROME; FERBON","url":"https://www.omim.org/entry/619699"},{"mim_id":"613745","title":"ANAPHASE-PROMOTING COMPLEX, SUBUNIT 10; ANAPC10","url":"https://www.omim.org/entry/613745"},{"mim_id":"606949","title":"ANAPHASE-PROMOTING COMPLEX, SUBUNIT 7; ANAPC7","url":"https://www.omim.org/entry/606949"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Microtubules","reliability":"Supported"},{"location":"Cytokinetic bridge","reliability":"Supported"},{"location":"Mitotic spindle","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ANAPC7"},"hgnc":{"alias_symbol":["APC7"],"prev_symbol":[]},"alphafold":{"accession":"Q9UJX3","domains":[{"cath_id":"1.25.40.10","chopping":"490-554","consensus_level":"medium","plddt":85.8145,"start":490,"end":554}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UJX3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UJX3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UJX3-F1-predicted_aligned_error_v6.png","plddt_mean":83.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANAPC7","jax_strain_url":"https://www.jax.org/strain/search?query=ANAPC7"},"sequence":{"accession":"Q9UJX3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UJX3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UJX3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UJX3"}},"corpus_meta":[{"pmid":"35176309","id":"PMC_35176309","title":"Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer.","date":"2022","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/35176309","citation_count":98,"is_preprint":false},{"pmid":"29969755","id":"PMC_29969755","title":"Circ-ANAPC7 is Upregulated in Acute Myeloid Leukemia and Appears to Target the MiR-181 Family.","date":"2018","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29969755","citation_count":74,"is_preprint":false},{"pmid":"26966728","id":"PMC_26966728","title":"Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines.","date":"2016","source":"Investigative and clinical urology","url":"https://pubmed.ncbi.nlm.nih.gov/26966728","citation_count":55,"is_preprint":false},{"pmid":"36497289","id":"PMC_36497289","title":"Accurate Diagnosis and Survival Prediction of Bladder Cancer Using Deep Learning on Histological Slides.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36497289","citation_count":34,"is_preprint":false},{"pmid":"23922952","id":"PMC_23922952","title":"The anaphase-promoting complex protein 5 (AnapC5) associates with A20 and inhibits IL-17-mediated signal transduction.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23922952","citation_count":20,"is_preprint":false},{"pmid":"33045833","id":"PMC_33045833","title":"Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS.","date":"2020","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/33045833","citation_count":18,"is_preprint":false},{"pmid":"33133141","id":"PMC_33133141","title":"Identification of the Significant Genes Regulated by Estrogen Receptor in Estrogen Receptor-Positive Breast Cancer and Their Expression Pattern Changes When Tamoxifen or Fulvestrant Resistance Occurs.","date":"2020","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/33133141","citation_count":15,"is_preprint":false},{"pmid":"34252097","id":"PMC_34252097","title":"Genes involved in immune, gene translation and chromatin organization pathways associated with Mycoplasma ovipneumoniae presence in nasal secretions of domestic sheep.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/34252097","citation_count":15,"is_preprint":false},{"pmid":"34879367","id":"PMC_34879367","title":"Using Circ-ANAPC7 as a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia.","date":"2021","source":"Acta haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/34879367","citation_count":13,"is_preprint":false},{"pmid":"35710353","id":"PMC_35710353","title":"miRNA-mRNA analysis of sheep adrenal glands reveals the network regulating reproduction.","date":"2022","source":"BMC genomic data","url":"https://pubmed.ncbi.nlm.nih.gov/35710353","citation_count":7,"is_preprint":false},{"pmid":"36126360","id":"PMC_36126360","title":"Identification of BRIP1, NSMCE2, ANAPC7, RAD18 and TTL from chromosome segregation gene set associated with hepatocellular carcinoma.","date":"2022","source":"Cancer genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36126360","citation_count":6,"is_preprint":false},{"pmid":"38440920","id":"PMC_38440920","title":"AP-1/C-FOS and AP-1/FRA2 differentially regulate early and late adipogenic differentiation of mesenchymal stem cells.","date":"2024","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38440920","citation_count":5,"is_preprint":false},{"pmid":"40022573","id":"PMC_40022573","title":"Utility of a Large Series of B-Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System.","date":"2025","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40022573","citation_count":3,"is_preprint":false},{"pmid":"36592213","id":"PMC_36592213","title":"Identification and validation of a PD-L1-related signature from mass spectrometry in gastric cancer.","date":"2023","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36592213","citation_count":2,"is_preprint":false},{"pmid":"39677807","id":"PMC_39677807","title":"Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39677807","citation_count":1,"is_preprint":false},{"pmid":"37304473","id":"PMC_37304473","title":"The Circular RNA Circ-ANAPC7 as a Biomarker for the Risk Stratification of Myelodysplastic Syndrome.","date":"2022","source":"Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion","url":"https://pubmed.ncbi.nlm.nih.gov/37304473","citation_count":1,"is_preprint":false},{"pmid":"41053005","id":"PMC_41053005","title":"Integrating genetic regulation and schizophrenia-specific splicing quantitative expression with GWAS prioritizes novel risk genes for schizophrenia.","date":"2025","source":"Translational psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/41053005","citation_count":1,"is_preprint":false},{"pmid":"40596695","id":"PMC_40596695","title":"Anapc5 and Anapc7 as genetic modifiers of KIF18A function in fertility and mitotic progression.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40596695","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.12.03.626395","title":"<i>Anapc5</i>  and  <i>Anapc7</i>  as genetic modifiers of KIF18A function in fertility and mitotic progression","date":"2024-12-04","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.03.626395","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12577,"output_tokens":1125,"usd":0.027303,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7727,"output_tokens":1872,"usd":0.042717,"stage2_stop_reason":"end_turn"},"total_usd":0.07002,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"ANAPC7 (APC7/AnapC7) was identified as a binding partner of both IL-17RA and IL-17RC cytoplasmic tails via yeast 2-hybrid screen. However, siRNA-mediated knockdown of AnapC7 exerted no detectable impact on IL-17 signaling. AnapC5, which associates with AnapC7, also bound IL-17RA and IL-17RC and functioned as a negative regulator of IL-17 signaling, and also associated with A20 (TNFAIP3).\",\n      \"method\": \"Yeast two-hybrid screen, siRNA knockdown, IL-17-induced gene expression assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — yeast 2-hybrid identification plus functional siRNA knockdown, but single lab and the ANAPC7 knockdown result was negative (no effect on IL-17 signaling)\",\n      \"pmids\": [\"23922952\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Genetic epistasis in mouse models and cell lines showed that co-depletion of ANAPC7 partially rescued KIF18A-depletion-induced mitotic arrest, while co-depletion of ANAPC5 exacerbated it. This establishes ANAPC7 as a functional component downstream or in opposition to KIF18A in mitotic progression, with ANAPC5 and ANAPC7 acting in opposing directions in the KIF18A-dependent mitotic pathway. A novel retroviral insertion in Anapc7 was identified that may influence its expression level and sensitivity to KIF18A loss.\",\n      \"method\": \"Genetic epistasis (double KD in cell lines), mouse genetic screen (strain background comparison), quantitative gene expression analysis\",\n      \"journal\": \"Scientific reports / bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in cell lines plus mouse genetic screen, replicated across preprint and peer-reviewed publication by same group, two orthogonal approaches\",\n      \"pmids\": [\"39677807\", \"40596695\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"C-FOS (AP-1 subunit) was shown by ChIP-seq to bind to the promoter of ANAPC7 and regulate its expression during mitotic clonal expansion in early adipogenesis of mesenchymal stem cells.\",\n      \"method\": \"Chromatin immunoprecipitation sequencing (ChIP-seq), gene expression analysis during adipogenesis\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, ChIP-seq identifies binding but functional validation of ANAPC7 regulation consequence is limited in the abstract\",\n      \"pmids\": [\"38440920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ANAPC7 was experimentally verified as a PD-L1 interactor by co-immunoprecipitation in gastric cancer cells, and ANAPC7 expression was associated with immune escape when NK-92 cells were co-cultured with gastric cancer cells.\",\n      \"method\": \"Co-immunoprecipitation (Co-IP), NK cell co-culture experiment\",\n      \"journal\": \"Journal of cancer research and clinical oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP identifying interaction, co-culture functional assay without detailed mechanistic follow-up, single lab\",\n      \"pmids\": [\"36592213\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANAPC7 is a subunit of the anaphase-promoting complex (APC/C) that participates in mitotic progression; its depletion partially rescues KIF18A-loss-induced mitotic arrest (acting epistatically opposite to ANAPC5), it physically interacts with IL-17 receptor subunits (though its knockdown does not affect IL-17 signaling), its promoter is directly bound and regulated by C-FOS during mitotic clonal expansion in adipogenesis, and it co-immunoprecipitates with PD-L1 in gastric cancer cells with potential implications for immune evasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANAPC7 functions as a component of the mitotic machinery, where genetic epistasis places it within the KIF18A-dependent pathway governing mitotic progression: co-depletion of ANAPC7 partially rescues the mitotic arrest caused by KIF18A loss, in direct opposition to ANAPC5, which exacerbates that arrest [#1]. Beyond this mitotic role, ANAPC7 has been captured in physical-interaction contexts that have not been resolved into a defined mechanism—it binds the cytoplasmic tails of IL-17RA and IL-17RC in a yeast two-hybrid screen, but its knockdown produces no detectable effect on IL-17 signaling [#0]. No catalytic activity, structural model, or substrate has been characterized for ANAPC7 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Testing whether ANAPC7 contributes to inflammatory receptor signaling, a yeast two-hybrid screen identified it as an IL-17 receptor binding partner, but functional knockdown showed it is dispensable for IL-17 signaling—placing its receptor association outside the IL-17 output pathway.\",\n      \"evidence\": \"Yeast two-hybrid screen with IL-17RA/IL-17RC cytoplasmic tails plus siRNA knockdown and IL-17-induced gene expression assays\",\n      \"pmids\": [\"23922952\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The biological consequence of the ANAPC7–IL-17R interaction is unresolved given the negative knockdown result\", \"No reciprocal validation or structural mapping of the interaction interface\", \"Functional contrast with ANAPC5 (a negative regulator binding the same receptors) leaves ANAPC7's role unexplained\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To define ANAPC7's role in mitosis, genetic epistasis showed that depleting it partially relieves KIF18A-loss-induced mitotic arrest while depleting ANAPC5 worsens it, establishing the two subunits as functionally opposing within the KIF18A-dependent mitotic pathway.\",\n      \"evidence\": \"Double knockdown in cell lines and a mouse genetic screen comparing strain backgrounds, with quantitative expression analysis of an Anapc7 retroviral insertion\",\n      \"pmids\": [\"39677807\", \"40596695\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The molecular basis for opposing ANAPC5 and ANAPC7 effects within the same complex is not defined\", \"Whether the rescue reflects altered APC/C substrate targeting is untested\", \"No direct substrate or biochemical readout connects ANAPC7 to the KIF18A axis\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Addressing how ANAPC7 expression is controlled, ChIP-seq showed C-FOS binds its promoter during mitotic clonal expansion in early adipogenesis, linking ANAPC7 transcription to an AP-1-driven proliferative program.\",\n      \"evidence\": \"ChIP-seq and expression analysis during mesenchymal stem cell adipogenesis\",\n      \"pmids\": [\"38440920\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Promoter binding does not establish a functional regulatory consequence for ANAPC7\", \"No knockdown or reporter assay confirms C-FOS-driven ANAPC7 transcription\", \"Downstream effect of ANAPC7 levels on adipogenesis is uncharacterized\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Probing a potential role in tumor immune evasion, co-immunoprecipitation identified ANAPC7 as a PD-L1 interactor in gastric cancer cells, with its expression linked to NK-cell-mediated immune escape.\",\n      \"evidence\": \"Co-immunoprecipitation and NK-92 co-culture assay in gastric cancer cells\",\n      \"pmids\": [\"36592213\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation of the PD-L1 interaction\", \"Mechanism connecting ANAPC7 to PD-L1 stability or function is not defined\", \"Causal contribution of ANAPC7 to immune escape is not established beyond correlation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of ANAPC7 within its complex—how it engages substrates and how it produces effects opposite to ANAPC5—remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No substrate or catalytic activity identified for ANAPC7\", \"No structural model of how ANAPC7 and ANAPC5 contribute oppositely to mitotic progression\", \"Mechanistic link between physical partners (IL-17R, PD-L1) and ANAPC7's mitotic function is unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"APC/C\"],\n    \"partners\": [\"IL17RA\", \"IL17RC\", \"ANAPC5\", \"CD274\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":1,"faith_total":1,"faith_pct":100.0}}