{"gene":"CHMP1A","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2001,"finding":"CHMP1 localizes to early endosomes and physically interacts with SKD1/VPS4, a protein directly linked to multivesicular body (MVB) sorting; overexpression of a CHMP1 fusion protein dilates endosomal compartments and disrupts endosomal marker distribution. Deletion of the yeast homolog CHM1 causes defective sorting of carboxypeptidases S and Y and produces abnormal multi-lamellar prevacuolar compartments, classifying it as a class E vacuolar protein sorting gene.","method":"Immunocytochemistry, biochemical fractionation, co-immunoprecipitation/physical interaction assay, yeast deletion genetics with sorting assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal biochemical interaction (physical interaction with SKD1/VPS4), localization by fractionation and ICC, genetic epistasis in yeast with defined phenotypic readout, multiple orthogonal methods","pmids":["11559748"],"is_preprint":false},{"year":2001,"finding":"CHMP1 distributes to both cytoplasm and nuclear matrix; overexpressed CHMP1 localizes to punctate subnuclear structures encapsulating condensed chromatin, recruits PcG protein BMI1 to these regions, and cooperates with vertebrate Pcl in a Xenopus PcG assay, implicating CHMP1 in stable gene silencing.","method":"Immunocytochemistry, biochemical fractionation, co-localization/recruitment assay, inducible overexpression in HEK293 cells, Xenopus embryo PcG functional assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence, BMI1 recruitment shown by co-localization, Xenopus functional assay; single lab, multiple orthogonal methods","pmids":["11559747"],"is_preprint":false},{"year":2012,"finding":"Loss-of-function mutations in human CHMP1A cause pontocerebellar hypoplasia; CHMP1A-mutant cells show impaired proliferation with increased INK4A expression and loss of normal BMI1-mediated INK4A repression (shown by ChIP). Morpholino knockdown of zebrafish chmp1a produced brain defects partially rescued by INK4A ortholog knockdown, placing CHMP1A upstream of BMI1-mediated INK4A repression in CNS progenitor proliferation.","method":"Human genetics (loss-of-function mutations), chromatin immunoprecipitation (ChIP), zebrafish morpholino knockdown with genetic rescue (epistasis)","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — human LOF mutations with cellular phenotype, ChIP mechanistic data, zebrafish epistasis rescue experiment, multiple orthogonal methods","pmids":["23023333"],"is_preprint":false},{"year":2018,"finding":"CHMP1A is required for intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs) and for secretion of Sonic Hedgehog (SHH) on a specific extracellular vesicle subtype containing AXL, RAB18, and TMED10 (ART-EVs); Chmp1a null mice show impaired SHH secretion and ILV formation, leading to reduced progenitor proliferation in cortex and cerebellum.","method":"Chmp1a null mouse model, electron microscopy (ILV/MVB analysis), EV proteomics, human cerebral organoid knockdown, SHH secretion assay","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined molecular phenotype (ILV formation, SHH secretion), EV proteomics identification of ART-EV subtype, organoid validation; multiple orthogonal methods, single lab","pmids":["30044992"],"is_preprint":false},{"year":2008,"finding":"Overexpression of Chmp1A in pancreatic ductal tumor cells inhibits cell growth and tumor xenograft formation, and strongly increases protein levels of p53 and phospho-p53; shRNA-mediated silencing promotes anchorage-independent growth and tumor formation, indicating Chmp1A acts as a tumor suppressor partly through p53 signaling.","method":"shRNA stable silencing, overexpression in PanC-1 cells, soft agar assay, xenograft assay, Western blot for p53/phospho-p53","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD and OE with defined cellular/in vivo phenotype, Western blot pathway readout; single lab, two orthogonal gain/loss-of-function approaches","pmids":["18787405"],"is_preprint":false},{"year":2011,"finding":"Overexpression of full-length CHMP1A activates ATM kinase (increased nuclear phospho-ATM) and downstream phospho-p53 in the nucleus; deletion of the nuclear localization signal (NLS) abolishes ATM activation and nuclear localization, indicating nuclear localization is required. ATM inactivation significantly reduces CHMP1A-mediated growth inhibition and p53 phosphorylation, placing ATM downstream of CHMP1A in a growth-suppressive pathway.","method":"Overexpression with NLS-deletion mutants, in vitro ATM kinase assay, p53 reporter assay, immunofluorescence co-localization, ATM inhibitor epistasis","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro ATM kinase assay plus domain mutagenesis (NLS deletion), ATM inhibitor epistasis, multiple readouts; single lab","pmids":["21705858"],"is_preprint":false},{"year":2013,"finding":"CHMP1A is phosphorylated at Ser179 and Ser182 in its C-terminal region, causing a mobility shift on SDS-PAGE. Ser-to-Ala mutations at these sites do not affect interaction with the binding partner IST1.","method":"Site-directed mutagenesis, phosphate-affinity PAGE, co-immunoprecipitation with IST1","journal":"Bioscience, biotechnology, and biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct mutagenesis and phospho-affinity gel identifying specific phosphorylation sites; single lab, single study","pmids":["23748770"],"is_preprint":false},{"year":2014,"finding":"Drosophila Chmp1 localizes to the late endosome and negatively regulates EGFR (DER) signaling; loss of Chmp1 in the wing causes a cell fate change from intervein to vein and decreases Blistered expression (a readout repressed by DER signaling), consistent with impaired receptor downregulation through the MVB/ESCRT-III pathway.","method":"Drosophila genetics (loss-of-function), immunofluorescence localization, genetic interaction analysis with DER pathway regulators, Blistered expression assay","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Drosophila ortholog LOF with defined cell fate phenotype, localization data, genetic interactions with EGFR pathway; single lab, multiple methods","pmids":["24753138"],"is_preprint":false},{"year":2021,"finding":"CHMP1A and DPEP1 regulate ferroptosis and cellular iron trafficking; mouse genetic models demonstrate causal roles for both genes in kidney disease, and cellular studies place both in a single ferroptosis pathway.","method":"Mouse genetic models (KO), single-cell chromatin accessibility, genome editing (fine mapping), cellular ferroptosis assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mouse genetic KO with defined disease phenotype, cellular pathway assays for ferroptosis; single lab but multiple orthogonal approaches","pmids":["34426578"],"is_preprint":false},{"year":2022,"finding":"CHMP1A overexpression in renal cell carcinoma cells suppresses mTOR pathway activity, upregulates p53 expression, and induces apoptosis via the MDM2/p53 pathway; p53 knockdown experiments show that p53 elevation is downstream of PI3K/mTOR inhibition by CHMP1A.","method":"Overexpression in A498/786-0 cells, Western blot (mTOR/p53/MDM2/Bax/Bcl-2), shRNA-p53 knockdown, colony formation and MTT assays, flow cytometry (apoptosis)","journal":"Genes & genomics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — overexpression with Western blot pathway readouts and p53 KD epistasis; single lab, single method per node","pmids":["35583792"],"is_preprint":false},{"year":2022,"finding":"Drosophila Chmp1 overexpression in the fat body decreases triglyceride storage, while fat-body-specific RNAi knockdown increases triglyceride accumulation; this effect is mediated through control of fat body cell number and size, not food consumption or lipid metabolic enzyme expression.","method":"Drosophila tissue-specific RNAi and overexpression (fat body), triglyceride assay, cell number/size measurement","journal":"Medical sciences (Basel, Switzerland)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Drosophila ortholog gain/loss-of-function with defined metabolic phenotype; single lab, single study, no direct molecular mechanism identified","pmids":["36649042"],"is_preprint":false}],"current_model":"CHMP1A is an ESCRT-III complex member that functions at multivesicular bodies to sort ubiquitinated cargo and form intraluminal vesicles via physical interaction with VPS4/SKD1; it also localizes to the nuclear matrix where it recruits BMI1 to condensed chromatin to repress INK4A, and in the nucleus activates ATM kinase in an NLS-dependent manner to phosphorylate p53, thereby suppressing proliferation—a pathway particularly critical for CNS progenitor maintenance and cerebellar development, and additionally required for SHH secretion on a specific ART-EV extracellular vesicle subtype."},"narrative":{"mechanistic_narrative":"CHMP1A is an ESCRT-III-class protein that operates at the boundary of two compartments — multivesicular bodies in the cytoplasm and the nuclear matrix — coupling endosomal membrane sorting to chromatin-dependent control of progenitor proliferation [PMID:11559748, PMID:11559747, PMID:23023333]. At early/late endosomes it physically associates with the AAA-ATPase SKD1/VPS4 and is required for multivesicular body sorting, where its loss disrupts endosomal architecture and cargo delivery, and its yeast and Drosophila orthologs behave as class E vacuolar sorting factors that downregulate receptors through the MVB pathway [PMID:11559748, PMID:24753138]. CHMP1A drives intraluminal vesicle formation and is required for secretion of Sonic Hedgehog on a distinct AXL/RAB18/TMED10-positive extracellular vesicle subtype; in its absence both ILV formation and SHH secretion fail, reducing cortical and cerebellar progenitor proliferation [PMID:30044992]. In a parallel nuclear role, CHMP1A localizes to the nuclear matrix, recruits the Polycomb protein BMI1 to condensed chromatin, and is required for BMI1-mediated repression of the INK4A locus; biallelic loss-of-function mutations in CHMP1A cause pontocerebellar hypoplasia, and mutant cells show derepressed INK4A and impaired proliferation, a defect placed upstream of BMI1/INK4A by zebrafish epistasis [PMID:11559747, PMID:23023333]. CHMP1A also restrains cell growth via a p53 axis: nuclear, NLS-dependent CHMP1A activates ATM kinase to phosphorylate p53, and acts as a tumor suppressor whose loss promotes anchorage-independent growth [PMID:18787405, PMID:21705858]. CHMP1A is phosphorylated at Ser179/Ser182 in its C-terminus, modification dispensable for binding the ESCRT partner IST1 [PMID:23748770].","teleology":[{"year":2001,"claim":"Established CHMP1 as an endosomal ESCRT-type sorting factor by linking it physically and genetically to the MVB machinery, defining its core membrane-trafficking identity.","evidence":"Co-immunoprecipitation with SKD1/VPS4, fractionation/ICC localization, and yeast CHM1 deletion with carboxypeptidase sorting assays","pmids":["11559748"],"confidence":"High","gaps":["Does not define the order of CHMP1A action within ESCRT-III assembly","No structural basis for the VPS4/SKD1 interaction"]},{"year":2001,"claim":"Revealed an unexpected nuclear function by showing CHMP1 partitions to the nuclear matrix and recruits BMI1 to condensed chromatin, raising the question of how an endosomal protein contributes to gene silencing.","evidence":"Fractionation, ICC, BMI1 recruitment co-localization, and Xenopus PcG functional assay","pmids":["11559747"],"confidence":"Medium","gaps":["Mechanism of CHMP1A nuclear import not defined here","Direct chromatin or BMI1 binding interface not resolved","Relationship between endosomal and nuclear pools unclear"]},{"year":2008,"claim":"Connected CHMP1A to growth suppression by demonstrating it behaves as a tumor suppressor acting through p53, extending its role beyond trafficking into proliferation control.","evidence":"shRNA silencing and overexpression in PanC-1 cells, soft agar and xenograft assays, Western blot for p53/phospho-p53","pmids":["18787405"],"confidence":"Medium","gaps":["Did not identify how CHMP1A elevates p53","Correlative phospho-p53 readout without upstream kinase identification"]},{"year":2011,"claim":"Identified the molecular route from CHMP1A to p53 by showing nuclear, NLS-dependent CHMP1A activates ATM kinase, mechanistically linking its nuclear localization to growth suppression.","evidence":"NLS-deletion mutants, in vitro ATM kinase assay, p53 reporter, IF co-localization, and ATM-inhibitor epistasis","pmids":["21705858"],"confidence":"Medium","gaps":["How CHMP1A activates ATM mechanistically is unresolved","Whether ATM activation is direct or via DNA damage signaling not established"]},{"year":2012,"claim":"Provided causal disease and mechanistic anchoring by showing CHMP1A loss-of-function causes pontocerebellar hypoplasia and acts upstream of BMI1-mediated INK4A repression in CNS progenitors.","evidence":"Human LOF genetics, ChIP for BMI1/INK4A, and zebrafish morpholino knockdown with INK4A-ortholog rescue","pmids":["23023333"],"confidence":"High","gaps":["How CHMP1A controls BMI1 chromatin recruitment in vivo not detailed","Connection between trafficking defects and chromatin phenotype not unified"]},{"year":2013,"claim":"Mapped post-translational regulation by identifying C-terminal phosphorylation sites and testing their role in partner binding, refining the protein's regulatory features.","evidence":"Site-directed mutagenesis, phosphate-affinity PAGE, and Co-IP with IST1","pmids":["23748770"],"confidence":"Medium","gaps":["Kinase responsible for Ser179/Ser182 phosphorylation unknown","Functional consequence of phosphorylation beyond IST1 binding untested"]},{"year":2018,"claim":"Unified the trafficking and developmental roles by showing CHMP1A drives ILV formation required for SHH secretion on a defined ART-EV subtype, explaining the progenitor proliferation defect.","evidence":"Chmp1a null mouse, electron microscopy, EV proteomics, cerebral organoid knockdown, and SHH secretion assay","pmids":["30044992"],"confidence":"High","gaps":["How ART-EV subtype specificity is determined not resolved","Relationship between SHH-EV secretion and the nuclear INK4A pathway not reconciled"]},{"year":2021,"claim":"Extended CHMP1A function into iron handling and cell death by placing it with DPEP1 in a ferroptosis pathway causally linked to kidney disease.","evidence":"Mouse KO models, single-cell chromatin accessibility, fine-mapping genome editing, and cellular ferroptosis assays","pmids":["34426578"],"confidence":"Medium","gaps":["Molecular mechanism linking CHMP1A to iron trafficking not defined","Whether ferroptosis role connects to ESCRT activity unknown"]},{"year":2022,"claim":"Proposed an mTOR-coupled apoptotic axis in renal carcinoma, positioning p53 elevation downstream of PI3K/mTOR inhibition by CHMP1A.","evidence":"Overexpression in A498/786-0 cells, Western blot, shRNA-p53 epistasis, colony/MTT and apoptosis assays","pmids":["35583792"],"confidence":"Low","gaps":["Single-lab overexpression study with single-method readouts per node","How CHMP1A inhibits PI3K/mTOR not established"]},{"year":2022,"claim":"Implicated the Chmp1 ortholog in tissue lipid storage by linking fat-body cell number and size to triglyceride accumulation, hinting at a broader role in organ growth.","evidence":"Drosophila fat-body tissue-specific RNAi and overexpression with triglyceride and cell-size measurements","pmids":["36649042"],"confidence":"Low","gaps":["No molecular mechanism identified","Relevance to mammalian CHMP1A untested"]},{"year":null,"claim":"How CHMP1A's cytoplasmic ESCRT-III/ILV function and its nuclear matrix/BMI1/ATM functions are mechanistically coordinated within one protein remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or interaction model unifying endosomal and nuclear pools","Signals partitioning CHMP1A between compartments unknown","Whether trafficking and chromatin defects share a common molecular cause undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,5]}],"localization":[{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0,7]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1,5]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,3,7]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[2,3]}],"complexes":["ESCRT-III"],"partners":["VPS4","BMI1","ATM","IST1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9HD42","full_name":"Charged multivesicular body protein 1a","aliases":["Chromatin-modifying protein 1a","CHMP1a","Vacuolar protein sorting-associated protein 46-1","Vps46-1","hVps46-1"],"length_aa":196,"mass_kda":21.7,"function":"Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing","subcellular_location":"Cytoplasm; Endosome membrane; Nucleus matrix","url":"https://www.uniprot.org/uniprotkb/Q9HD42/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CHMP1A","classification":"Not Classified","n_dependent_lines":352,"n_total_lines":1208,"dependency_fraction":0.2913907284768212},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000131165","cell_line_id":"CID000772","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"nuclear_punctae","grade":2}],"interactors":[{"gene":"CLTB","stoichiometry":0.2},{"gene":"HNRNPA2B1","stoichiometry":0.2},{"gene":"VPS4A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000772","total_profiled":1310},"omim":[{"mim_id":"621486","title":"MICROTUBULE-INTERACTING AND TRAFFICKING DOMAIN-CONTAINING PROTEIN 1; MITD1","url":"https://www.omim.org/entry/621486"},{"mim_id":"616434","title":"IST1 FACTOR ASSOCIATED WITH ESCRT-III; IST1","url":"https://www.omim.org/entry/616434"},{"mim_id":"614961","title":"PONTOCEREBELLAR HYPOPLASIA, TYPE 8; PCH8","url":"https://www.omim.org/entry/614961"},{"mim_id":"610901","title":"CHARGED MULTIVESICULAR BODY PROTEIN 6; CHMP6","url":"https://www.omim.org/entry/610901"},{"mim_id":"610900","title":"CHARGED MULTIVESICULAR BODY PROTEIN 5; CHMP5","url":"https://www.omim.org/entry/610900"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Centrosome","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CHMP1A"},"hgnc":{"alias_symbol":["KIAA0047","CHMP1","Vps46A"],"prev_symbol":["PRSM1","PCOLN3"]},"alphafold":{"accession":"Q9HD42","domains":[{"cath_id":"1.10.287","chopping":"138-196","consensus_level":"medium","plddt":64.2332,"start":138,"end":196}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HD42","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HD42-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HD42-F1-predicted_aligned_error_v6.png","plddt_mean":77.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CHMP1A","jax_strain_url":"https://www.jax.org/strain/search?query=CHMP1A"},"sequence":{"accession":"Q9HD42","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9HD42.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9HD42/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HD42"}},"corpus_meta":[{"pmid":"11559748","id":"PMC_11559748","title":"CHMP1 functions as a member of a newly defined family of vesicle trafficking proteins.","date":"2001","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11559748","citation_count":128,"is_preprint":false},{"pmid":"11559747","id":"PMC_11559747","title":"CHMP1 is a novel nuclear matrix protein affecting chromatin structure and cell-cycle progression.","date":"2001","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11559747","citation_count":100,"is_preprint":false},{"pmid":"23023333","id":"PMC_23023333","title":"CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development.","date":"2012","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23023333","citation_count":83,"is_preprint":false},{"pmid":"30044992","id":"PMC_30044992","title":"The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/30044992","citation_count":81,"is_preprint":false},{"pmid":"34426578","id":"PMC_34426578","title":"A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34426578","citation_count":65,"is_preprint":false},{"pmid":"18787405","id":"PMC_18787405","title":"Chmp1A functions as a novel tumor suppressor gene in human embryonic kidney and ductal pancreatic tumor cells.","date":"2008","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/18787405","citation_count":46,"is_preprint":false},{"pmid":"29463243","id":"PMC_29463243","title":"Anacardic acid inhibits pancreatic cancer cell growth, and potentiates chemotherapeutic effect by Chmp1A - ATM - p53 signaling pathway.","date":"2018","source":"BMC complementary and alternative medicine","url":"https://pubmed.ncbi.nlm.nih.gov/29463243","citation_count":20,"is_preprint":false},{"pmid":"22261332","id":"PMC_22261332","title":"Chmp1A acts as a tumor suppressor gene that inhibits proliferation of renal cell carcinoma.","date":"2012","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/22261332","citation_count":16,"is_preprint":false},{"pmid":"24753138","id":"PMC_24753138","title":"The Drosophila Chmp1 protein determines wing cell fate through regulation of epidermal growth factor receptor signaling.","date":"2014","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/24753138","citation_count":14,"is_preprint":false},{"pmid":"21705858","id":"PMC_21705858","title":"Chromatin modifying protein 1A (Chmp1A) of the endosomal sorting complex required for transport (ESCRT)-III family activates ataxia telangiectasia mutated (ATM) for PanC-1 cell growth inhibition.","date":"2011","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21705858","citation_count":14,"is_preprint":false},{"pmid":"8863740","id":"PMC_8863740","title":"Molecular cloning, expression and chromosomal localization of a human gene encoding a 33 kDa putative metallopeptidase (PRSM1).","date":"1996","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/8863740","citation_count":13,"is_preprint":false},{"pmid":"15179039","id":"PMC_15179039","title":"Molecular characterization of NbCHMP1 encoding a homolog of human CHMP1 in Nicotiana benthamiana.","date":"2004","source":"Molecules and cells","url":"https://pubmed.ncbi.nlm.nih.gov/15179039","citation_count":11,"is_preprint":false},{"pmid":"31894018","id":"PMC_31894018","title":"miR-17 regulates the proliferation and differentiation of retinal progenitor cells by targeting CHMP1A.","date":"2019","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/31894018","citation_count":7,"is_preprint":false},{"pmid":"35583792","id":"PMC_35583792","title":"CHMP1A suppresses the growth of renal cell carcinoma cells via regulation of the PI3K/mTOR/p53 signaling pathway.","date":"2022","source":"Genes & genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35583792","citation_count":6,"is_preprint":false},{"pmid":"36135830","id":"PMC_36135830","title":"Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster.","date":"2022","source":"Medical sciences (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36135830","citation_count":4,"is_preprint":false},{"pmid":"16094257","id":"PMC_16094257","title":"Association analysis of CHMP1.5 genetic variation and bipolar disorder.","date":"2005","source":"Psychiatric genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16094257","citation_count":3,"is_preprint":false},{"pmid":"36509868","id":"PMC_36509868","title":"A novel homozygous CHMP1A variant arising from segmental uniparental disomy causes pontocerebellar hypoplasia type 8.","date":"2022","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36509868","citation_count":3,"is_preprint":false},{"pmid":"36649042","id":"PMC_36649042","title":"The ESCRT-III Protein Chmp1 Regulates Lipid Storage in the Drosophila Fat Body.","date":"2022","source":"Medical sciences (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36649042","citation_count":2,"is_preprint":false},{"pmid":"23748770","id":"PMC_23748770","title":"Identification of phosphorylation sites in the C-terminal region of charged multivesicular body protein 1A (CHMP1A).","date":"2013","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23748770","citation_count":2,"is_preprint":false},{"pmid":"37789895","id":"PMC_37789895","title":"Novel bi-allelic variants of CHMP1A contribute to pontocerebellar hypoplasia type 8: additional clinical and genetic evidence.","date":"2023","source":"Frontiers in neurology","url":"https://pubmed.ncbi.nlm.nih.gov/37789895","citation_count":1,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.02.25337157","title":"Human Kidney Alternative Splicing Information Illuminates Cardiovascular-Kidney-Metabolic Syndrome Risk","date":"2025-10-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.02.25337157","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11926,"output_tokens":2953,"usd":0.040037,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10357,"output_tokens":3596,"usd":0.070843,"stage2_stop_reason":"end_turn"},"total_usd":0.11088,"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\": 2001,\n      \"finding\": \"CHMP1 localizes to early endosomes and physically interacts with SKD1/VPS4, a protein directly linked to multivesicular body (MVB) sorting; overexpression of a CHMP1 fusion protein dilates endosomal compartments and disrupts endosomal marker distribution. Deletion of the yeast homolog CHM1 causes defective sorting of carboxypeptidases S and Y and produces abnormal multi-lamellar prevacuolar compartments, classifying it as a class E vacuolar protein sorting gene.\",\n      \"method\": \"Immunocytochemistry, biochemical fractionation, co-immunoprecipitation/physical interaction assay, yeast deletion genetics with sorting assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal biochemical interaction (physical interaction with SKD1/VPS4), localization by fractionation and ICC, genetic epistasis in yeast with defined phenotypic readout, multiple orthogonal methods\",\n      \"pmids\": [\"11559748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"CHMP1 distributes to both cytoplasm and nuclear matrix; overexpressed CHMP1 localizes to punctate subnuclear structures encapsulating condensed chromatin, recruits PcG protein BMI1 to these regions, and cooperates with vertebrate Pcl in a Xenopus PcG assay, implicating CHMP1 in stable gene silencing.\",\n      \"method\": \"Immunocytochemistry, biochemical fractionation, co-localization/recruitment assay, inducible overexpression in HEK293 cells, Xenopus embryo PcG functional assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence, BMI1 recruitment shown by co-localization, Xenopus functional assay; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"11559747\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Loss-of-function mutations in human CHMP1A cause pontocerebellar hypoplasia; CHMP1A-mutant cells show impaired proliferation with increased INK4A expression and loss of normal BMI1-mediated INK4A repression (shown by ChIP). Morpholino knockdown of zebrafish chmp1a produced brain defects partially rescued by INK4A ortholog knockdown, placing CHMP1A upstream of BMI1-mediated INK4A repression in CNS progenitor proliferation.\",\n      \"method\": \"Human genetics (loss-of-function mutations), chromatin immunoprecipitation (ChIP), zebrafish morpholino knockdown with genetic rescue (epistasis)\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — human LOF mutations with cellular phenotype, ChIP mechanistic data, zebrafish epistasis rescue experiment, multiple orthogonal methods\",\n      \"pmids\": [\"23023333\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CHMP1A is required for intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs) and for secretion of Sonic Hedgehog (SHH) on a specific extracellular vesicle subtype containing AXL, RAB18, and TMED10 (ART-EVs); Chmp1a null mice show impaired SHH secretion and ILV formation, leading to reduced progenitor proliferation in cortex and cerebellum.\",\n      \"method\": \"Chmp1a null mouse model, electron microscopy (ILV/MVB analysis), EV proteomics, human cerebral organoid knockdown, SHH secretion assay\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined molecular phenotype (ILV formation, SHH secretion), EV proteomics identification of ART-EV subtype, organoid validation; multiple orthogonal methods, single lab\",\n      \"pmids\": [\"30044992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Overexpression of Chmp1A in pancreatic ductal tumor cells inhibits cell growth and tumor xenograft formation, and strongly increases protein levels of p53 and phospho-p53; shRNA-mediated silencing promotes anchorage-independent growth and tumor formation, indicating Chmp1A acts as a tumor suppressor partly through p53 signaling.\",\n      \"method\": \"shRNA stable silencing, overexpression in PanC-1 cells, soft agar assay, xenograft assay, Western blot for p53/phospho-p53\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD and OE with defined cellular/in vivo phenotype, Western blot pathway readout; single lab, two orthogonal gain/loss-of-function approaches\",\n      \"pmids\": [\"18787405\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Overexpression of full-length CHMP1A activates ATM kinase (increased nuclear phospho-ATM) and downstream phospho-p53 in the nucleus; deletion of the nuclear localization signal (NLS) abolishes ATM activation and nuclear localization, indicating nuclear localization is required. ATM inactivation significantly reduces CHMP1A-mediated growth inhibition and p53 phosphorylation, placing ATM downstream of CHMP1A in a growth-suppressive pathway.\",\n      \"method\": \"Overexpression with NLS-deletion mutants, in vitro ATM kinase assay, p53 reporter assay, immunofluorescence co-localization, ATM inhibitor epistasis\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro ATM kinase assay plus domain mutagenesis (NLS deletion), ATM inhibitor epistasis, multiple readouts; single lab\",\n      \"pmids\": [\"21705858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CHMP1A is phosphorylated at Ser179 and Ser182 in its C-terminal region, causing a mobility shift on SDS-PAGE. Ser-to-Ala mutations at these sites do not affect interaction with the binding partner IST1.\",\n      \"method\": \"Site-directed mutagenesis, phosphate-affinity PAGE, co-immunoprecipitation with IST1\",\n      \"journal\": \"Bioscience, biotechnology, and biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct mutagenesis and phospho-affinity gel identifying specific phosphorylation sites; single lab, single study\",\n      \"pmids\": [\"23748770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Drosophila Chmp1 localizes to the late endosome and negatively regulates EGFR (DER) signaling; loss of Chmp1 in the wing causes a cell fate change from intervein to vein and decreases Blistered expression (a readout repressed by DER signaling), consistent with impaired receptor downregulation through the MVB/ESCRT-III pathway.\",\n      \"method\": \"Drosophila genetics (loss-of-function), immunofluorescence localization, genetic interaction analysis with DER pathway regulators, Blistered expression assay\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Drosophila ortholog LOF with defined cell fate phenotype, localization data, genetic interactions with EGFR pathway; single lab, multiple methods\",\n      \"pmids\": [\"24753138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CHMP1A and DPEP1 regulate ferroptosis and cellular iron trafficking; mouse genetic models demonstrate causal roles for both genes in kidney disease, and cellular studies place both in a single ferroptosis pathway.\",\n      \"method\": \"Mouse genetic models (KO), single-cell chromatin accessibility, genome editing (fine mapping), cellular ferroptosis assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mouse genetic KO with defined disease phenotype, cellular pathway assays for ferroptosis; single lab but multiple orthogonal approaches\",\n      \"pmids\": [\"34426578\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CHMP1A overexpression in renal cell carcinoma cells suppresses mTOR pathway activity, upregulates p53 expression, and induces apoptosis via the MDM2/p53 pathway; p53 knockdown experiments show that p53 elevation is downstream of PI3K/mTOR inhibition by CHMP1A.\",\n      \"method\": \"Overexpression in A498/786-0 cells, Western blot (mTOR/p53/MDM2/Bax/Bcl-2), shRNA-p53 knockdown, colony formation and MTT assays, flow cytometry (apoptosis)\",\n      \"journal\": \"Genes & genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — overexpression with Western blot pathway readouts and p53 KD epistasis; single lab, single method per node\",\n      \"pmids\": [\"35583792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Drosophila Chmp1 overexpression in the fat body decreases triglyceride storage, while fat-body-specific RNAi knockdown increases triglyceride accumulation; this effect is mediated through control of fat body cell number and size, not food consumption or lipid metabolic enzyme expression.\",\n      \"method\": \"Drosophila tissue-specific RNAi and overexpression (fat body), triglyceride assay, cell number/size measurement\",\n      \"journal\": \"Medical sciences (Basel, Switzerland)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Drosophila ortholog gain/loss-of-function with defined metabolic phenotype; single lab, single study, no direct molecular mechanism identified\",\n      \"pmids\": [\"36649042\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CHMP1A is an ESCRT-III complex member that functions at multivesicular bodies to sort ubiquitinated cargo and form intraluminal vesicles via physical interaction with VPS4/SKD1; it also localizes to the nuclear matrix where it recruits BMI1 to condensed chromatin to repress INK4A, and in the nucleus activates ATM kinase in an NLS-dependent manner to phosphorylate p53, thereby suppressing proliferation—a pathway particularly critical for CNS progenitor maintenance and cerebellar development, and additionally required for SHH secretion on a specific ART-EV extracellular vesicle subtype.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CHMP1A is an ESCRT-III-class protein that operates at the boundary of two compartments — multivesicular bodies in the cytoplasm and the nuclear matrix — coupling endosomal membrane sorting to chromatin-dependent control of progenitor proliferation [#0, #1, #2]. At early/late endosomes it physically associates with the AAA-ATPase SKD1/VPS4 and is required for multivesicular body sorting, where its loss disrupts endosomal architecture and cargo delivery, and its yeast and Drosophila orthologs behave as class E vacuolar sorting factors that downregulate receptors through the MVB pathway [#0, #7]. CHMP1A drives intraluminal vesicle formation and is required for secretion of Sonic Hedgehog on a distinct AXL/RAB18/TMED10-positive extracellular vesicle subtype; in its absence both ILV formation and SHH secretion fail, reducing cortical and cerebellar progenitor proliferation [#3]. In a parallel nuclear role, CHMP1A localizes to the nuclear matrix, recruits the Polycomb protein BMI1 to condensed chromatin, and is required for BMI1-mediated repression of the INK4A locus; biallelic loss-of-function mutations in CHMP1A cause pontocerebellar hypoplasia, and mutant cells show derepressed INK4A and impaired proliferation, a defect placed upstream of BMI1/INK4A by zebrafish epistasis [#1, #2]. CHMP1A also restrains cell growth via a p53 axis: nuclear, NLS-dependent CHMP1A activates ATM kinase to phosphorylate p53, and acts as a tumor suppressor whose loss promotes anchorage-independent growth [#4, #5]. CHMP1A is phosphorylated at Ser179/Ser182 in its C-terminus, modification dispensable for binding the ESCRT partner IST1 [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established CHMP1 as an endosomal ESCRT-type sorting factor by linking it physically and genetically to the MVB machinery, defining its core membrane-trafficking identity.\",\n      \"evidence\": \"Co-immunoprecipitation with SKD1/VPS4, fractionation/ICC localization, and yeast CHM1 deletion with carboxypeptidase sorting assays\",\n      \"pmids\": [\"11559748\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define the order of CHMP1A action within ESCRT-III assembly\", \"No structural basis for the VPS4/SKD1 interaction\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Revealed an unexpected nuclear function by showing CHMP1 partitions to the nuclear matrix and recruits BMI1 to condensed chromatin, raising the question of how an endosomal protein contributes to gene silencing.\",\n      \"evidence\": \"Fractionation, ICC, BMI1 recruitment co-localization, and Xenopus PcG functional assay\",\n      \"pmids\": [\"11559747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of CHMP1A nuclear import not defined here\", \"Direct chromatin or BMI1 binding interface not resolved\", \"Relationship between endosomal and nuclear pools unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Connected CHMP1A to growth suppression by demonstrating it behaves as a tumor suppressor acting through p53, extending its role beyond trafficking into proliferation control.\",\n      \"evidence\": \"shRNA silencing and overexpression in PanC-1 cells, soft agar and xenograft assays, Western blot for p53/phospho-p53\",\n      \"pmids\": [\"18787405\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not identify how CHMP1A elevates p53\", \"Correlative phospho-p53 readout without upstream kinase identification\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identified the molecular route from CHMP1A to p53 by showing nuclear, NLS-dependent CHMP1A activates ATM kinase, mechanistically linking its nuclear localization to growth suppression.\",\n      \"evidence\": \"NLS-deletion mutants, in vitro ATM kinase assay, p53 reporter, IF co-localization, and ATM-inhibitor epistasis\",\n      \"pmids\": [\"21705858\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How CHMP1A activates ATM mechanistically is unresolved\", \"Whether ATM activation is direct or via DNA damage signaling not established\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Provided causal disease and mechanistic anchoring by showing CHMP1A loss-of-function causes pontocerebellar hypoplasia and acts upstream of BMI1-mediated INK4A repression in CNS progenitors.\",\n      \"evidence\": \"Human LOF genetics, ChIP for BMI1/INK4A, and zebrafish morpholino knockdown with INK4A-ortholog rescue\",\n      \"pmids\": [\"23023333\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How CHMP1A controls BMI1 chromatin recruitment in vivo not detailed\", \"Connection between trafficking defects and chromatin phenotype not unified\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mapped post-translational regulation by identifying C-terminal phosphorylation sites and testing their role in partner binding, refining the protein's regulatory features.\",\n      \"evidence\": \"Site-directed mutagenesis, phosphate-affinity PAGE, and Co-IP with IST1\",\n      \"pmids\": [\"23748770\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase responsible for Ser179/Ser182 phosphorylation unknown\", \"Functional consequence of phosphorylation beyond IST1 binding untested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Unified the trafficking and developmental roles by showing CHMP1A drives ILV formation required for SHH secretion on a defined ART-EV subtype, explaining the progenitor proliferation defect.\",\n      \"evidence\": \"Chmp1a null mouse, electron microscopy, EV proteomics, cerebral organoid knockdown, and SHH secretion assay\",\n      \"pmids\": [\"30044992\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How ART-EV subtype specificity is determined not resolved\", \"Relationship between SHH-EV secretion and the nuclear INK4A pathway not reconciled\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extended CHMP1A function into iron handling and cell death by placing it with DPEP1 in a ferroptosis pathway causally linked to kidney disease.\",\n      \"evidence\": \"Mouse KO models, single-cell chromatin accessibility, fine-mapping genome editing, and cellular ferroptosis assays\",\n      \"pmids\": [\"34426578\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism linking CHMP1A to iron trafficking not defined\", \"Whether ferroptosis role connects to ESCRT activity unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Proposed an mTOR-coupled apoptotic axis in renal carcinoma, positioning p53 elevation downstream of PI3K/mTOR inhibition by CHMP1A.\",\n      \"evidence\": \"Overexpression in A498/786-0 cells, Western blot, shRNA-p53 epistasis, colony/MTT and apoptosis assays\",\n      \"pmids\": [\"35583792\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single-lab overexpression study with single-method readouts per node\", \"How CHMP1A inhibits PI3K/mTOR not established\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Implicated the Chmp1 ortholog in tissue lipid storage by linking fat-body cell number and size to triglyceride accumulation, hinting at a broader role in organ growth.\",\n      \"evidence\": \"Drosophila fat-body tissue-specific RNAi and overexpression with triglyceride and cell-size measurements\",\n      \"pmids\": [\"36649042\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No molecular mechanism identified\", \"Relevance to mammalian CHMP1A untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CHMP1A's cytoplasmic ESCRT-III/ILV function and its nuclear matrix/BMI1/ATM functions are mechanistically coordinated within one protein remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural or interaction model unifying endosomal and nuclear pools\", \"Signals partitioning CHMP1A between compartments unknown\", \"Whether trafficking and chromatin defects share a common molecular cause undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 7]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 3, 7]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\"ESCRT-III\"],\n    \"partners\": [\"VPS4\", \"BMI1\", \"ATM\", \"IST1\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}