{"gene":"CNTRL","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2002,"finding":"CEP110 (CNTRL) localizes to a specific domain of the centrosome corresponding to the open end of the centrosome tube, which is the site of protein addition during maturation of a daughter centrosome into a mother centrosome. Microinjection of anti-CEP110 antibodies into metaphase cells disrupted reformation of the tubular conformation of centrosomal proteins following cell division and impaired centrosome function as a microtubule organizing center (MTOC).","method":"Immunofluorescence mapping, co-localization with CEP250/c-Nap1, antibody microinjection into HeLa and PtK2 cells with functional MTOC readout","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct antibody microinjection loss-of-function with defined cellular phenotypes (MTOC disruption, loss of tubular conformation), multiple cell lines, and spatial mapping with orthogonal markers","pmids":["11956314"],"is_preprint":false},{"year":2000,"finding":"CEP110 (CNTRL) is a centrosome-associated coiled-coil protein (994 amino acids) with four leucine zipper motifs. The CEP110-FGFR1 fusion protein arising from t(8;9)(p12;q33) retains the leucine zipper motifs of CEP110 and the catalytic domain of FGFR1, resulting in constitutive (ligand-independent) tyrosine kinase activity and cytoplasmic localization.","method":"Molecular cloning, transient expression, kinase activity assay, immunofluorescence localization of fusion protein","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — kinase activity assay and localization performed in transfected cells in a single study; constitutive activity established experimentally","pmids":["10688839"],"is_preprint":false},{"year":2006,"finding":"Hook2 directly binds to the C-terminal domain of centriolin/CEP110 (CNTRL) at the centrosome. The C-terminal domain of centriolin/CEP110, when overexpressed, alters the distribution of endogenous hook2. Mislocalized hook2 perturbs centrosomal and pericentrosomal proteins, and interference with hook2 function (which depends on its interaction with CEP110) results in loss of radial microtubule organization and defective microtubule regrowth after nocodazole washout.","method":"Direct binding assay (pulldown), co-localization, dominant-negative overexpression of CEP110 C-terminal domain, microtubule regrowth assay after nocodazole treatment","journal":"Traffic (Copenhagen, Denmark)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding shown by pulldown and functional perturbation with C-terminal domain overexpression; single lab but multiple orthogonal methods","pmids":["17140400"],"is_preprint":false},{"year":2025,"finding":"CRISPR/Cas9-mediated disruption of the centriolin/CEP110 gene (CNTRL) in rhabdomyosarcoma cells (CCL-136) leads to cell cycle arrest and apoptotic cell death, establishing a required role for CNTRL in rhabdomyosarcoma cell proliferation and viability.","method":"CRISPR/Cas9 gene disruption, cell viability assay, cell cycle analysis in rhabdomyosarcoma cell line","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined cellular phenotype (cell cycle arrest, apoptosis) in a single study from a single lab","pmids":["41370122"],"is_preprint":false},{"year":2025,"finding":"A novel splicing variant of CNTRL::FGFR1 fusion (involving an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1) retains the kinase domain of FGFR1 and leads to its constitutive activation, demonstrating that alternative splicing at the fusion breakpoint can still produce an oncogenic, constitutively active kinase.","method":"Targeted transcriptome sequencing, RT-PCR, Sanger sequencing","journal":"Journal of hematopathology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — constitutive activation inferred from structural retention of kinase domain, not directly assayed in this report; single case","pmids":["41266899"],"is_preprint":false}],"current_model":"CNTRL/CEP110 is a coiled-coil centrosomal protein that localizes to both ends of the centrosome tube in mother centrioles and exclusively to the closed end in daughter centrioles, where it is required for centrosome maturation and MTOC function; its C-terminal domain directly binds Hook2 to support centrosomal structure and radial microtubule organization, and its loss causes cell cycle arrest and apoptosis; in oncogenesis, its leucine zipper motifs drive oligomerization-dependent constitutive activation of kinase partners when fused to FGFR1 or PDGFRB."},"narrative":{"mechanistic_narrative":"CNTRL (CEP110/centriolin) is a centrosome-associated coiled-coil protein required for centrosome maturation and microtubule-organizing center (MTOC) function [PMID:11956314]. It localizes to a specific domain corresponding to the open end of the centrosome tube—the site of protein addition during maturation of a daughter into a mother centrosome—and antibody-mediated interference disrupts reformation of the tubular conformation of centrosomal proteins after division and impairs MTOC activity [PMID:11956314]. Its C-terminal domain directly binds Hook2 at the centrosome; this interaction is needed to maintain proper distribution of centrosomal and pericentrosomal proteins and to support radial microtubule organization and microtubule regrowth [PMID:17140400]. CNTRL function is required for proliferation and viability, as gene disruption in rhabdomyosarcoma cells causes cell cycle arrest and apoptosis [PMID:41370122]. In oncogenesis, CNTRL contributes its four leucine zipper motifs to fusion proteins with FGFR1: the CEP110-FGFR1 fusion from t(8;9)(p12;q33) retains these oligomerization motifs and the FGFR1 catalytic domain, producing constitutive, ligand-independent tyrosine kinase activity and cytoplasmic mislocalization [PMID:10688839].","teleology":[{"year":2000,"claim":"Established CNTRL as a centrosomal coiled-coil protein whose leucine zipper motifs can drive oncogenic kinase activation when fused to FGFR1, defining the molecular basis of a leukemia-associated translocation.","evidence":"Molecular cloning, transient expression, kinase activity assay, and immunofluorescence of the CEP110-FGFR1 fusion from t(8;9)(p12;q33)","pmids":["10688839"],"confidence":"Medium","gaps":["Endogenous CNTRL function not addressed","Oligomerization mechanism inferred from leucine zippers but not directly dissected"]},{"year":2002,"claim":"Defined where CNTRL acts on the centrosome and showed it is functionally required for MTOC activity, linking its position at the maturing open end of the centrosome tube to centrosome maturation.","evidence":"Immunofluorescence mapping with CEP250/c-Nap1, antibody microinjection into HeLa and PtK2 cells with MTOC readout","pmids":["11956314"],"confidence":"High","gaps":["Molecular partners mediating maturation not identified here","Antibody microinjection does not pinpoint the affected protein domain"]},{"year":2006,"claim":"Identified a direct molecular partner (Hook2) bound by the CNTRL C-terminal domain, providing a mechanistic link between CNTRL and radial microtubule organization.","evidence":"Pulldown binding assay, co-localization, dominant-negative C-terminal overexpression, and nocodazole microtubule regrowth assay","pmids":["17140400"],"confidence":"Medium","gaps":["Single lab; reciprocal in vivo validation limited","Stoichiometry and structural basis of the CNTRL-Hook2 interaction unresolved"]},{"year":2025,"claim":"Demonstrated that CNTRL is required for cancer cell proliferation and survival, extending its centrosomal role to a dependency in rhabdomyosarcoma.","evidence":"CRISPR/Cas9 gene disruption with viability and cell cycle analysis in CCL-136 rhabdomyosarcoma cells","pmids":["41370122"],"confidence":"Medium","gaps":["Single cell line and single study","Mechanistic link between centrosomal defect and apoptosis not resolved"]},{"year":2025,"claim":"Showed that alternative splicing at the CNTRL::FGFR1 breakpoint can still yield a kinase-domain-retaining fusion, broadening the structural variants capable of oncogenic activation.","evidence":"Targeted transcriptome sequencing, RT-PCR, and Sanger sequencing of a single case","pmids":["41266899"],"confidence":"Low","gaps":["Constitutive activation inferred from kinase-domain retention, not directly assayed","Single case report without functional validation"]},{"year":null,"claim":"How CNTRL coordinates Hook2 binding with centrosome maturation at the molecular level, and how its loss mechanistically triggers cell cycle arrest, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of CNTRL or its complexes","Pathway connecting MTOC defect to apoptosis uncharacterized","Full interactome beyond Hook2 unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,3]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[1,4]}],"complexes":[],"partners":["HOOK2","FGFR1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q7Z7A1","full_name":"Centriolin","aliases":["Centrosomal protein 1","Centrosomal protein of 110 kDa","Cep110"],"length_aa":2325,"mass_kda":268.9,"function":"Involved in cell cycle progression and cytokinesis. During the late steps of cytokinesis, anchors exocyst and SNARE complexes at the midbody, thereby allowing secretory vesicle-mediated abscission","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Midbody, Midbody ring","url":"https://www.uniprot.org/uniprotkb/Q7Z7A1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CNTRL","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"MSN","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CNTRL","total_profiled":1310},"omim":[{"mim_id":"605496","title":"CENTRIOLIN; CNTRL","url":"https://www.omim.org/entry/605496"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Flagellar centriole","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"lymphoid tissue","ntpm":20.3},{"tissue":"testis","ntpm":28.4}],"url":"https://www.proteinatlas.org/search/CNTRL"},"hgnc":{"alias_symbol":[],"prev_symbol":["CEP1","CEP110"]},"alphafold":{"accession":"Q7Z7A1","domains":[{"cath_id":"3.80.10.10","chopping":"86-274","consensus_level":"high","plddt":81.149,"start":86,"end":274},{"cath_id":"-","chopping":"1583-1605_1630-1718","consensus_level":"medium","plddt":72.2991,"start":1583,"end":1718},{"cath_id":"1.10.287","chopping":"491-609","consensus_level":"medium","plddt":78.7092,"start":491,"end":609}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z7A1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z7A1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q7Z7A1-F1-predicted_aligned_error_v6.png","plddt_mean":60.59},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CNTRL","jax_strain_url":"https://www.jax.org/strain/search?query=CNTRL"},"sequence":{"accession":"Q7Z7A1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q7Z7A1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q7Z7A1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q7Z7A1"}},"corpus_meta":[{"pmid":"11956314","id":"PMC_11956314","title":"CEP110 and ninein are located in a specific domain of the centrosome associated with centrosome maturation.","date":"2002","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11956314","citation_count":125,"is_preprint":false},{"pmid":"10688839","id":"PMC_10688839","title":"FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).","date":"2000","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/10688839","citation_count":122,"is_preprint":false},{"pmid":"17140400","id":"PMC_17140400","title":"Hook2 localizes to the centrosome, binds directly to centriolin/CEP110 and contributes to centrosomal function.","date":"2006","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/17140400","citation_count":55,"is_preprint":false},{"pmid":"15087377","id":"PMC_15087377","title":"NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.","date":"2004","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/15087377","citation_count":51,"is_preprint":false},{"pmid":"18295660","id":"PMC_18295660","title":"8p11 myeloproliferative syndrome preceded by t(8;9)(p11;q33), CEP110/FGFR1 fusion transcript: morphologic, molecular, and cytogenetic characterization of myeloid neoplasms associated with eosinophilia and FGFR1 abnormality.","date":"2008","source":"Cancer genetics and cytogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/18295660","citation_count":21,"is_preprint":false},{"pmid":"25803811","id":"PMC_25803811","title":"Screening of drugs to treat 8p11 myeloproliferative syndrome using patient-derived induced pluripotent stem cells with fusion gene CEP110-FGFR1.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25803811","citation_count":18,"is_preprint":false},{"pmid":"18096225","id":"PMC_18096225","title":"Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110-FGFR1 fusion: report of a new case and review of the literature.","date":"2007","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/18096225","citation_count":17,"is_preprint":false},{"pmid":"28242791","id":"PMC_28242791","title":"Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement.","date":"2017","source":"The oncologist","url":"https://pubmed.ncbi.nlm.nih.gov/28242791","citation_count":11,"is_preprint":false},{"pmid":"31250523","id":"PMC_31250523","title":"Targeted therapy and disease monitoring in CNTRL-FGFR1-driven leukaemia.","date":"2019","source":"Pediatric blood & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31250523","citation_count":5,"is_preprint":false},{"pmid":"26418991","id":"PMC_26418991","title":"[8p11 myeloproliferative syndrome with CEP110-FGFR1 fusion in a patient].","date":"2015","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26418991","citation_count":1,"is_preprint":false},{"pmid":"41370122","id":"PMC_41370122","title":"Disruption of the centriolin/Cep110 gene (CNTRL) with CRISPR/Cas9 leads to cell cycle arrest and cell death of rhabdomyosarcoma cells in vitro.","date":"2025","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/41370122","citation_count":0,"is_preprint":false},{"pmid":"41266899","id":"PMC_41266899","title":"A novel splicing variant of CNTRL::FGFR1 in myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1.","date":"2025","source":"Journal of hematopathology","url":"https://pubmed.ncbi.nlm.nih.gov/41266899","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7700,"output_tokens":1462,"usd":0.022515,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8118,"output_tokens":2037,"usd":0.045757,"stage2_stop_reason":"end_turn"},"total_usd":0.068272,"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\": 2002,\n      \"finding\": \"CEP110 (CNTRL) localizes to a specific domain of the centrosome corresponding to the open end of the centrosome tube, which is the site of protein addition during maturation of a daughter centrosome into a mother centrosome. Microinjection of anti-CEP110 antibodies into metaphase cells disrupted reformation of the tubular conformation of centrosomal proteins following cell division and impaired centrosome function as a microtubule organizing center (MTOC).\",\n      \"method\": \"Immunofluorescence mapping, co-localization with CEP250/c-Nap1, antibody microinjection into HeLa and PtK2 cells with functional MTOC readout\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct antibody microinjection loss-of-function with defined cellular phenotypes (MTOC disruption, loss of tubular conformation), multiple cell lines, and spatial mapping with orthogonal markers\",\n      \"pmids\": [\"11956314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"CEP110 (CNTRL) is a centrosome-associated coiled-coil protein (994 amino acids) with four leucine zipper motifs. The CEP110-FGFR1 fusion protein arising from t(8;9)(p12;q33) retains the leucine zipper motifs of CEP110 and the catalytic domain of FGFR1, resulting in constitutive (ligand-independent) tyrosine kinase activity and cytoplasmic localization.\",\n      \"method\": \"Molecular cloning, transient expression, kinase activity assay, immunofluorescence localization of fusion protein\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — kinase activity assay and localization performed in transfected cells in a single study; constitutive activity established experimentally\",\n      \"pmids\": [\"10688839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Hook2 directly binds to the C-terminal domain of centriolin/CEP110 (CNTRL) at the centrosome. The C-terminal domain of centriolin/CEP110, when overexpressed, alters the distribution of endogenous hook2. Mislocalized hook2 perturbs centrosomal and pericentrosomal proteins, and interference with hook2 function (which depends on its interaction with CEP110) results in loss of radial microtubule organization and defective microtubule regrowth after nocodazole washout.\",\n      \"method\": \"Direct binding assay (pulldown), co-localization, dominant-negative overexpression of CEP110 C-terminal domain, microtubule regrowth assay after nocodazole treatment\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding shown by pulldown and functional perturbation with C-terminal domain overexpression; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"17140400\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CRISPR/Cas9-mediated disruption of the centriolin/CEP110 gene (CNTRL) in rhabdomyosarcoma cells (CCL-136) leads to cell cycle arrest and apoptotic cell death, establishing a required role for CNTRL in rhabdomyosarcoma cell proliferation and viability.\",\n      \"method\": \"CRISPR/Cas9 gene disruption, cell viability assay, cell cycle analysis in rhabdomyosarcoma cell line\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined cellular phenotype (cell cycle arrest, apoptosis) in a single study from a single lab\",\n      \"pmids\": [\"41370122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A novel splicing variant of CNTRL::FGFR1 fusion (involving an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1) retains the kinase domain of FGFR1 and leads to its constitutive activation, demonstrating that alternative splicing at the fusion breakpoint can still produce an oncogenic, constitutively active kinase.\",\n      \"method\": \"Targeted transcriptome sequencing, RT-PCR, Sanger sequencing\",\n      \"journal\": \"Journal of hematopathology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — constitutive activation inferred from structural retention of kinase domain, not directly assayed in this report; single case\",\n      \"pmids\": [\"41266899\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CNTRL/CEP110 is a coiled-coil centrosomal protein that localizes to both ends of the centrosome tube in mother centrioles and exclusively to the closed end in daughter centrioles, where it is required for centrosome maturation and MTOC function; its C-terminal domain directly binds Hook2 to support centrosomal structure and radial microtubule organization, and its loss causes cell cycle arrest and apoptosis; in oncogenesis, its leucine zipper motifs drive oligomerization-dependent constitutive activation of kinase partners when fused to FGFR1 or PDGFRB.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CNTRL (CEP110/centriolin) is a centrosome-associated coiled-coil protein required for centrosome maturation and microtubule-organizing center (MTOC) function [#0]. It localizes to a specific domain corresponding to the open end of the centrosome tube—the site of protein addition during maturation of a daughter into a mother centrosome—and antibody-mediated interference disrupts reformation of the tubular conformation of centrosomal proteins after division and impairs MTOC activity [#0]. Its C-terminal domain directly binds Hook2 at the centrosome; this interaction is needed to maintain proper distribution of centrosomal and pericentrosomal proteins and to support radial microtubule organization and microtubule regrowth [#2]. CNTRL function is required for proliferation and viability, as gene disruption in rhabdomyosarcoma cells causes cell cycle arrest and apoptosis [#3]. In oncogenesis, CNTRL contributes its four leucine zipper motifs to fusion proteins with FGFR1: the CEP110-FGFR1 fusion from t(8;9)(p12;q33) retains these oligomerization motifs and the FGFR1 catalytic domain, producing constitutive, ligand-independent tyrosine kinase activity and cytoplasmic mislocalization [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established CNTRL as a centrosomal coiled-coil protein whose leucine zipper motifs can drive oncogenic kinase activation when fused to FGFR1, defining the molecular basis of a leukemia-associated translocation.\",\n      \"evidence\": \"Molecular cloning, transient expression, kinase activity assay, and immunofluorescence of the CEP110-FGFR1 fusion from t(8;9)(p12;q33)\",\n      \"pmids\": [\"10688839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endogenous CNTRL function not addressed\", \"Oligomerization mechanism inferred from leucine zippers but not directly dissected\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined where CNTRL acts on the centrosome and showed it is functionally required for MTOC activity, linking its position at the maturing open end of the centrosome tube to centrosome maturation.\",\n      \"evidence\": \"Immunofluorescence mapping with CEP250/c-Nap1, antibody microinjection into HeLa and PtK2 cells with MTOC readout\",\n      \"pmids\": [\"11956314\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular partners mediating maturation not identified here\", \"Antibody microinjection does not pinpoint the affected protein domain\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identified a direct molecular partner (Hook2) bound by the CNTRL C-terminal domain, providing a mechanistic link between CNTRL and radial microtubule organization.\",\n      \"evidence\": \"Pulldown binding assay, co-localization, dominant-negative C-terminal overexpression, and nocodazole microtubule regrowth assay\",\n      \"pmids\": [\"17140400\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; reciprocal in vivo validation limited\", \"Stoichiometry and structural basis of the CNTRL-Hook2 interaction unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated that CNTRL is required for cancer cell proliferation and survival, extending its centrosomal role to a dependency in rhabdomyosarcoma.\",\n      \"evidence\": \"CRISPR/Cas9 gene disruption with viability and cell cycle analysis in CCL-136 rhabdomyosarcoma cells\",\n      \"pmids\": [\"41370122\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell line and single study\", \"Mechanistic link between centrosomal defect and apoptosis not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed that alternative splicing at the CNTRL::FGFR1 breakpoint can still yield a kinase-domain-retaining fusion, broadening the structural variants capable of oncogenic activation.\",\n      \"evidence\": \"Targeted transcriptome sequencing, RT-PCR, and Sanger sequencing of a single case\",\n      \"pmids\": [\"41266899\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Constitutive activation inferred from kinase-domain retention, not directly assayed\", \"Single case report without functional validation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CNTRL coordinates Hook2 binding with centrosome maturation at the molecular level, and how its loss mechanistically triggers cell cycle arrest, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of CNTRL or its complexes\", \"Pathway connecting MTOC defect to apoptosis uncharacterized\", \"Full interactome beyond Hook2 unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"HOOK2\", \"FGFR1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}