{"gene":"TCHP","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2010,"finding":"Trichoplein/mitostatin (TpMs/TCHP) is present at the interface between mitochondria and endoplasmic reticulum (ER), as shown by subcellular fractionation and immunostaining. Its expression promotes mitochondrial fragmentation and loosens ER-mitochondria tethering, while its silencing has opposite effects. This tethering regulation requires Mitofusin 2 (Mfn2) and functionally inhibits apoptosis triggered by Ca2+-dependent stimuli that require ER-mitochondria juxtaposition.","method":"Subcellular fractionation, immunostaining, genetic knockdown/overexpression, Ca2+-dependent apoptosis assays, epistasis with Mfn2","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (fractionation, imaging, functional rescue, genetic epistasis) in single study with rigorous controls","pmids":["20930847"],"is_preprint":false},{"year":2011,"finding":"Trichoplein (TCHP) localizes to the subdistal-to-medial zone of both mother and daughter centrioles in proliferating cells. It directly binds the centrosomal proteins Odf2 and ninein. Trichoplein depletion abolishes ninein recruitment at the subdistal end (but not Odf2), while Odf2 depletion prevents trichoplein recruitment to the mother centriole. Both trichoplein and Odf2 depletion impair microtubule anchoring at the centrosome, placing trichoplein in a complex with Odf2 and ninein that controls MT-anchoring activity.","method":"Immunocytochemistry, co-immunoprecipitation/binding assays, siRNA knockdown with functional microtubule anchoring readout","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — reciprocal depletion epistasis plus direct binding assays plus functional MT-anchoring readout","pmids":["21325031"],"is_preprint":false},{"year":2014,"finding":"The CRL3-KCTD17 ubiquitin E3 ligase complex polyubiquitylates trichoplein (TCHP) at K50/K57 on mother centrioles, targeting it for proteasomal degradation. This ubiquitin-proteasome-mediated removal of trichoplein inactivates Aurora A kinase at the mother centriole, thereby initiating the first step of axoneme extension during ciliogenesis. Proteasome inhibition or expression of non-ubiquitylatable trichoplein (K50/57R) blocks ciliogenesis at the axoneme extension step. KCTD17 was identified as the substrate adaptor through two-step global E3 screening.","method":"E3 ligase screen, mutagenesis (K50/57R non-ubiquitylatable mutant), proteasome inhibitor treatment, siRNA knockdown, ciliogenesis assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 — mutagenesis of ubiquitylation sites combined with E3 ligase identification and functional ciliogenesis rescue assays","pmids":["25270598"],"is_preprint":false},{"year":2014,"finding":"Soluble decorin induces mitophagy in breast carcinoma cells through a pathway involving PGC-1α and mitostatin (TpMs/TCHP). PGC-1α binds MITOSTATIN mRNA to stabilize it, increasing mitostatin protein levels. Depletion of mitostatin blocks decorin-evoked or rapamycin-evoked mitophagy and increases VEGFA production, establishing mitostatin as a key regulator of tumor cell mitophagy and angiostasis downstream of the decorin/Met axis.","method":"siRNA knockdown, mRNA stability assays, RIP (RNA immunoprecipitation), mitophagy assays, VEGFA measurement","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods (RIP, KD, functional mitophagy assay) but single lab","pmids":["24403067"],"is_preprint":false},{"year":2016,"finding":"Ndel1, a dynein modulator, localizes at the subdistal appendage of the mother centriole and acts as an upstream regulator of the trichoplein (TCHP)–Aurora A pathway. In proliferating cells, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation; this is rescued by forced trichoplein expression or KCTD17 co-knockdown. Serum starvation triggers transient Ndel1 degradation, which precedes trichoplein disappearance and allows ciliogenesis. Forced Ndel1 expression suppresses trichoplein degradation and axoneme extension, mimicking trichoplein overexpression.","method":"siRNA knockdown, overexpression rescue, immunofluorescence, in vivo Ndel1-hypomorphic mouse model (kidney tubular epithelia)","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis with rescue experiments and in vivo validation in hypomorphic mice","pmids":["26880200"],"is_preprint":false},{"year":2020,"finding":"Silencing of TpMs (TCHP) in cancer cells causes chromosome mis-segregation, DNA damage, and chromosomal instability. TpMs interacts with Mad2, and its depletion results in decreased levels of Mad2 and Cyclin B1 proteins, consistent with defective spindle assembly checkpoint activation and aberrant mitotic progression.","method":"siRNA knockdown, chromosome segregation assays, DNA damage markers, co-immunoprecipitation (TpMs–Mad2 interaction), Western blot for Mad2 and Cyclin B1","journal":"Cancers","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP for Mad2 interaction plus functional chromosomal instability readouts, single lab","pmids":["32316593"],"is_preprint":false},{"year":2022,"finding":"TpMs (TCHP) depletion causes alterations in the 3D architecture of telomeres and changes the spatial arrangement of chromosomes and other nuclear components in colon cancer HCT116 cells, as revealed by 3D structured illumination microscopy. These nuclear architecture changes are consistent with the chromosomal instability phenotype and connect TpMs tumor suppressor function to maintenance of proper telomere and nuclear organization.","method":"3D structured illumination microscopy (3D-SIM), 3D imaging of telomere architecture in TpMs-depleted cells","journal":"Biomedicines","confidence":"Medium","confidence_rationale":"Tier 3 — single method (super-resolution microscopy) with localization/structural readout, single lab","pmids":["35884905"],"is_preprint":false},{"year":2026,"finding":"TCHP (trichoplein) is markedly upregulated in hepatocellular carcinoma. Mechanistically, TCHP localizes to centrosomes and promotes liquid-liquid phase separation (LLPS)-driven condensate formation with Aurora A kinase (AURKA), thereby enhancing AURKA activation and safeguarding mitotic fidelity. TCHP overexpression accelerates hepatocarcinogenesis in mice, while its depletion suppresses tumor growth by inducing mitotic defects. TCHP inhibition also sensitizes liver cancer cells to the AURKA inhibitor alisertib, defining a TCHP–AURKA oncogenic axis.","method":"Mouse hepatocarcinogenesis overexpression model, siRNA/shRNA depletion, LLPS condensate assays, co-localization at centrosomes, AURKA activity assays, drug synergy with alisertib","journal":"Cell death & disease","confidence":"High","confidence_rationale":"Tier 2 — in vivo mouse model plus LLPS mechanistic assays plus AURKA activity readout and pharmacological validation","pmids":["42034602"],"is_preprint":false}],"current_model":"TCHP (trichoplein/mitostatin) is a centrosomal scaffold protein that suppresses primary ciliogenesis in proliferating cells by activating Aurora A kinase (a function terminated by CRL3-KCTD17-mediated ubiquitination and proteasomal degradation of TCHP); it anchors microtubules at the centrosome via a complex with Odf2 and ninein, regulates ER-mitochondria tethering and mitophagy in a Mfn2-dependent manner, maintains chromosomal stability through interaction with the spindle assembly checkpoint protein Mad2, and in cancer can drive oncogenesis by forming LLPS condensates with AURKA at centrosomes to enhance its activation."},"narrative":{"teleology":[{"year":2010,"claim":"The first mechanistic insight into TCHP revealed an unexpected non-centrosomal role: TCHP resides at ER–mitochondria contact sites and modulates their tethering and mitochondrial fission through Mfn2, establishing it as a regulator of organelle communication and Ca2+-dependent apoptosis.","evidence":"Subcellular fractionation, immunostaining, genetic knockdown/overexpression, and Mfn2 epistasis in mammalian cells","pmids":["20930847"],"confidence":"High","gaps":["Direct binding interface between TCHP and Mfn2 not mapped","Whether ER–mitochondria tethering function operates independently of centrosomal roles is unknown","In vivo validation of the ER–mitochondria phenotype not performed"]},{"year":2011,"claim":"Establishing TCHP's centrosomal function, direct binding to Odf2 and ninein was demonstrated, placing TCHP in a hierarchical complex (Odf2 → TCHP → ninein) required for microtubule anchoring at the centrosome.","evidence":"Co-immunoprecipitation, reciprocal siRNA depletion epistasis, and functional MT-anchoring assays","pmids":["21325031"],"confidence":"High","gaps":["Structural basis of the Odf2–TCHP–ninein interaction not resolved","Whether TCHP's MT-anchoring role is cell-type specific remains untested"]},{"year":2014,"claim":"Two independent studies resolved how TCHP is removed to permit ciliogenesis and linked TCHP to mitophagy: CRL3-KCTD17 ubiquitinates TCHP at K50/K57 to trigger its proteasomal degradation and inactivate Aurora A, initiating axoneme extension; separately, PGC-1α stabilizes TCHP mRNA to increase its protein levels, which are required for decorin-evoked mitophagy and suppression of VEGFA.","evidence":"Global E3 screen with non-ubiquitylatable K50/57R mutant and ciliogenesis rescue (ciliogenesis); RIP, siRNA, mitophagy and VEGFA assays in breast carcinoma cells (mitophagy)","pmids":["25270598","24403067"],"confidence":"High","gaps":["Whether TCHP directly activates Aurora A or acts through an intermediary scaffold is not fully defined","Mitophagy function of TCHP established only in breast carcinoma cells by a single lab","Relationship between TCHP's ciliogenesis-suppressive and mitophagy-promoting functions not clarified"]},{"year":2016,"claim":"Ndel1 was placed upstream of TCHP in the ciliogenesis pathway: serum starvation triggers transient Ndel1 degradation, which precedes TCHP loss from the mother centriole, establishing a temporal cascade (Ndel1 → TCHP → Aurora A) that gates ciliogenesis initiation.","evidence":"siRNA epistasis with rescue, immunofluorescence, and in vivo validation in Ndel1-hypomorphic mouse kidneys","pmids":["26880200"],"confidence":"High","gaps":["How Ndel1 physically stabilizes TCHP at the mother centriole is not determined","Whether Ndel1-TCHP epistasis operates in tissues beyond kidney tubular epithelium is unknown"]},{"year":2020,"claim":"TCHP was linked to mitotic fidelity: its depletion causes chromosome mis-segregation and DNA damage, and it interacts with the spindle assembly checkpoint protein Mad2, with loss reducing Mad2 and Cyclin B1 levels.","evidence":"Co-immunoprecipitation, siRNA depletion, chromosome segregation assays and DNA damage markers in cancer cells","pmids":["32316593"],"confidence":"Medium","gaps":["Mad2 interaction demonstrated by a single Co-IP without reciprocal pull-down or structural validation","Whether TCHP regulates Mad2 stability versus localization is not distinguished","Unclear whether chromosomal instability arises from SAC defects or from centrosomal/MT-anchoring dysfunction"]},{"year":2022,"claim":"Super-resolution imaging extended the chromosomal instability phenotype by showing that TCHP depletion alters 3D telomere architecture and nuclear organization, connecting its function to higher-order genome maintenance.","evidence":"3D structured illumination microscopy in TCHP-depleted HCT116 cells","pmids":["35884905"],"confidence":"Medium","gaps":["Single imaging method without independent functional confirmation of telomere dysfunction","Whether telomere architectural changes are a direct consequence of TCHP loss or secondary to chromosomal instability is unresolved"]},{"year":2026,"claim":"In hepatocellular carcinoma, TCHP was shown to form LLPS condensates with AURKA at centrosomes, enhancing AURKA activation and promoting oncogenesis; TCHP overexpression accelerated hepatocarcinogenesis in mice, and its inhibition synergized with the AURKA inhibitor alisertib.","evidence":"Mouse overexpression hepatocarcinogenesis model, LLPS condensate assays, AURKA activity readouts, and alisertib drug synergy","pmids":["42034602"],"confidence":"High","gaps":["LLPS condensate composition beyond TCHP–AURKA not characterized","Whether LLPS-mediated AURKA activation is relevant in non-cancerous proliferating cells is unknown","Structural determinants of TCHP phase separation not identified"]},{"year":null,"claim":"It remains unresolved how TCHP's centrosomal, ER–mitochondria, and SAC-related functions are coordinated—whether distinct pools of TCHP operate at different subcellular sites and how they are partitioned in different cell states.","evidence":"","pmids":[],"confidence":"Low","gaps":["No study has simultaneously tracked TCHP pools at centrosomes, ER–mitochondria contacts, and the spindle","Post-translational modification map beyond K50/K57 ubiquitination is incomplete","No structural model of TCHP exists"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,2,4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,7]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1,2,4,7]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,3]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,2,4]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[5,7]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[7]}],"complexes":["Odf2–trichoplein–ninein centrosomal complex"],"partners":["ODF2","NIN","AURKA","KCTD17","NDEL1","MFN2","MAD2L1"],"other_free_text":[]},"mechanistic_narrative":"TCHP (trichoplein) is a centrosome-associated scaffold protein that coordinates ciliogenesis, microtubule organization, mitochondrial dynamics, and mitotic fidelity. At the subdistal-to-medial zone of centrioles, TCHP forms a complex with Odf2 and ninein to anchor microtubules and activates Aurora A kinase to suppress primary cilium formation in proliferating cells; CRL3-KCTD17-mediated ubiquitination and proteasomal degradation of TCHP at K50/K57 terminates this suppression, permitting axoneme extension during ciliogenesis [PMID:21325031, PMID:25270598, PMID:26880200]. TCHP also localizes to ER–mitochondria contact sites where it regulates mitochondrial morphology and tethering in an Mfn2-dependent manner, functioning as a downstream effector of decorin-evoked mitophagy [PMID:20930847, PMID:24403067]. In cancer, TCHP interacts with Mad2 to support spindle assembly checkpoint function and chromosomal stability, and when overexpressed drives oncogenesis through liquid–liquid phase separation condensates with AURKA at centrosomes that enhance AURKA activation [PMID:32316593, PMID:42034602]."},"prefetch_data":{"uniprot":{"accession":"Q9BT92","full_name":"Trichoplein keratin filament-binding protein","aliases":["Mitochondrial protein with oncostatic activity","Mitostatin","Tumor suppressor protein"],"length_aa":498,"mass_kda":61.1,"function":"Tumor suppressor which has the ability to inhibit cell growth and be pro-apoptotic during cell stress. Inhibits cell growth in bladder and prostate cancer cells by a down-regulation of HSPB1 by inhibiting its phosphorylation. May act as a 'capping' or 'branching' protein for keratin filaments in the cell periphery. May regulate K8/K18 filament and desmosome organization mainly at the apical or peripheral regions of simple epithelial cells (PubMed:15731013, PubMed:18931701). Is a negative regulator of ciliogenesis (PubMed:25270598)","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm; Cell membrane; Mitochondrion; Cell junction, desmosome; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","url":"https://www.uniprot.org/uniprotkb/Q9BT92/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TCHP","classification":"Not Classified","n_dependent_lines":6,"n_total_lines":1208,"dependency_fraction":0.004966887417218543},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TCHP","total_profiled":1310},"omim":[{"mim_id":"616386","title":"POTASSIUM CHANNEL TETRAMERIZATION DOMAIN-CONTAINING PROTEIN 17; KCTD17","url":"https://www.omim.org/entry/616386"},{"mim_id":"614449","title":"PROTOCADHERIN 20; PCDH20","url":"https://www.omim.org/entry/614449"},{"mim_id":"612654","title":"TRICHOPLEIN; TCHP","url":"https://www.omim.org/entry/612654"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Primary cilium","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Mid piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TCHP"},"hgnc":{"alias_symbol":["MGC10854","TpMs"],"prev_symbol":[]},"alphafold":{"accession":"Q9BT92","domains":[{"cath_id":"1.20.5","chopping":"26-55","consensus_level":"medium","plddt":83.509,"start":26,"end":55},{"cath_id":"1.20.5","chopping":"60-124","consensus_level":"medium","plddt":82.7268,"start":60,"end":124}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BT92","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BT92-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BT92-F1-predicted_aligned_error_v6.png","plddt_mean":83.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TCHP","jax_strain_url":"https://www.jax.org/strain/search?query=TCHP"},"sequence":{"accession":"Q9BT92","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BT92.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BT92/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BT92"}},"corpus_meta":[{"pmid":"31877523","id":"PMC_31877523","title":"Functionally graded and multi-morphology sheet TPMS lattices: Design, manufacturing, and mechanical properties.","date":"2019","source":"Journal of the mechanical behavior of biomedical materials","url":"https://pubmed.ncbi.nlm.nih.gov/31877523","citation_count":63,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32957226","id":"PMC_32957226","title":"On the permeability of TPMS scaffolds.","date":"2020","source":"Journal of the mechanical behavior of biomedical materials","url":"https://pubmed.ncbi.nlm.nih.gov/32957226","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31013656","id":"PMC_31013656","title":"Permeability versus Design in TPMS Scaffolds.","date":"2019","source":"Materials (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31013656","citation_count":42,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"37099921","id":"PMC_37099921","title":"3D printed TPMS structural PLA/GO scaffold: Process parameter optimization, porous structure, mechanical and biological properties.","date":"2023","source":"Journal of the mechanical behavior of biomedical materials","url":"https://pubmed.ncbi.nlm.nih.gov/37099921","citation_count":41,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32053711","id":"PMC_32053711","title":"In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32053711","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25175253","id":"PMC_25175253","title":"Investigating internal architecture effect in plastic deformation and failure for TPMS-based scaffolds using simulation methods and experimental procedure.","date":"2014","source":"Materials science & engineering. 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interacts with Mad2, and TpMs depletion results in decreased levels of Mad2 and Cyclin B1 proteins, consistent with defective spindle assembly checkpoint activation.\",\n      \"method\": \"siRNA knockdown in cancer cells, co-immunoprecipitation (TpMs-Mad2 interaction), immunoblotting for Mad2 and Cyclin B1, mitotic analysis\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — single lab, KD with defined phenotype plus Co-IP binding partner identification, moderate methods\",\n      \"pmids\": [\"32316593\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TpMs/TCHP depletion causes alterations in the 3D architecture of telomeres and changes the spatial arrangement of chromosomes and other nuclear components, linking TpMs tumor suppressor function to maintenance of proper telomere and nuclear architecture.\",\n      \"method\": \"3D imaging and 3D Structured Illumination Microscopy (3D-SIM) of TpMs-depleted cell lines (HCT116 colon cancer cells)\",\n      \"journal\": \"Biomedicines\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single imaging approach, localization finding without full mechanistic pathway placement\",\n      \"pmids\": [\"35884905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TCHP (Trichoplein) localizes to centrosomes and promotes liquid-liquid phase separation (LLPS)-driven condensate formation with AURKA, thereby enhancing AURKA activation and safeguarding mitotic fidelity; TCHP overexpression accelerates hepatocarcinogenesis in mice while its depletion suppresses tumor growth by inducing mitotic defects.\",\n      \"method\": \"In vivo mouse hepatocarcinogenesis model, TCHP overexpression and depletion functional assays, centrosome localization imaging, LLPS condensate assay with AURKA, co-localization and interaction studies\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — single lab, multiple orthogonal methods (in vivo model, LLPS assay, localization, functional depletion with phenotype)\",\n      \"pmids\": [\"42034602\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TCHP (Trichoplein/TpMs) is a centrosomal protein that localizes to centrosomes and promotes AURKA activation through liquid-liquid phase separation-driven condensate formation; it also interacts with the spindle assembly checkpoint protein Mad2 to regulate mitotic fidelity, and its depletion causes chromosome mis-segregation, chromosomal instability, and altered nuclear/telomere architecture, consistent with a tumor suppressor role in maintaining genomic stability.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries from KEPT papers only.\n\n**Classification:**\n\n- Papers [1]-[6], [8]-[9], [12]-[16], [18]-[22], [26]-[27], [29]-[41], [43]-[44], [48]-[53] in the main corpus: EXCLUDE — these describe TPMS as \"Triply Periodic Minimal Surfaces\" (engineering/materials science), or as breast cancer chemotherapy regimen \"TCHP\" (docetaxel/carboplatin/trastuzumab/pertuzumab), or other unrelated meanings.\n- Paper [7] (PMID:23911284): EXCLUDE — \"TChP\" = Targeted Chromatin Purification technique, not the TCHP protein.\n- Paper [17] (PMID:32316593): KEEP — describes Trichoplein (TpMs/TCHP protein), chromosome mis-segregation, Mad2 interaction.\n- Paper [28] (PMID:35884905): KEEP — describes TpMs/TCHP protein, telomere architecture, nuclear organization.\n- Paper [45] (PMID:42034602): KEEP — describes TCHP centrosomal protein, AURKA interaction, liver cancer.\n- Paper [54] (bio_10.1101_2025.06.03.655413): EXCLUDE — \"TPMs\" = thioglycollate-elicited peritoneal macrophages, not TCHP protein.\n- Paper [55]: EXCLUDE — Tpm4.2 = tropomyosin, not TCHP.\n- Paper [56]: EXCLUDE — TPMs = Transition Probability Matrices.\n\n**gene2pubmed papers:**\n- PMID:16189514, 12477932, 26186194, 28514442, 25416956, 32296183, 14702039, 33961781, 21873635, 29395067, 26638075, 24255178, 34079125, 21145461, 28611215, 21399614, 34800366, 25281560, 27173435, 21516116, 25900982: KEEP as interactome/proximity data that may mention TCHP interactions — but most are large-scale studies; extract only TCHP-specific findings.\n- PMID:25270598: KEEP — directly about trichoplein/KCTD17/Aurora A/ciliogenesis.\n- PMID:18029348: KEEP — subcellular localization atlas.\n- PMID:24403067: KEEP — mitostatin/TCHP role in mitophagy.\n- PMID:29080840: KEEP — mitostatin/TCHP in mitophagy.\n- PMID:21325031: KEEP — trichoplein at centrosome, Odf2/ninein binding.\n- PMID:26880200: KEEP — Ndel1/trichoplein/Aurora A pathway.\n- PMID:31515488: KEEP — may contain TCHP interaction data.\n- PMID:20930847: KEEP — TpMs regulates ER-mitochondria juxtaposition.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"Trichoplein/mitostatin (TpMs/TCHP) is present at the interface between mitochondria and endoplasmic reticulum (ER), as shown by subcellular fractionation and immunostaining. Its expression promotes mitochondrial fragmentation and loosens ER-mitochondria tethering, while its silencing has opposite effects. This tethering regulation requires Mitofusin 2 (Mfn2) and functionally inhibits apoptosis triggered by Ca2+-dependent stimuli that require ER-mitochondria juxtaposition.\",\n      \"method\": \"Subcellular fractionation, immunostaining, genetic knockdown/overexpression, Ca2+-dependent apoptosis assays, epistasis with Mfn2\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (fractionation, imaging, functional rescue, genetic epistasis) in single study with rigorous controls\",\n      \"pmids\": [\"20930847\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Trichoplein (TCHP) localizes to the subdistal-to-medial zone of both mother and daughter centrioles in proliferating cells. It directly binds the centrosomal proteins Odf2 and ninein. Trichoplein depletion abolishes ninein recruitment at the subdistal end (but not Odf2), while Odf2 depletion prevents trichoplein recruitment to the mother centriole. Both trichoplein and Odf2 depletion impair microtubule anchoring at the centrosome, placing trichoplein in a complex with Odf2 and ninein that controls MT-anchoring activity.\",\n      \"method\": \"Immunocytochemistry, co-immunoprecipitation/binding assays, siRNA knockdown with functional microtubule anchoring readout\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal depletion epistasis plus direct binding assays plus functional MT-anchoring readout\",\n      \"pmids\": [\"21325031\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The CRL3-KCTD17 ubiquitin E3 ligase complex polyubiquitylates trichoplein (TCHP) at K50/K57 on mother centrioles, targeting it for proteasomal degradation. This ubiquitin-proteasome-mediated removal of trichoplein inactivates Aurora A kinase at the mother centriole, thereby initiating the first step of axoneme extension during ciliogenesis. Proteasome inhibition or expression of non-ubiquitylatable trichoplein (K50/57R) blocks ciliogenesis at the axoneme extension step. KCTD17 was identified as the substrate adaptor through two-step global E3 screening.\",\n      \"method\": \"E3 ligase screen, mutagenesis (K50/57R non-ubiquitylatable mutant), proteasome inhibitor treatment, siRNA knockdown, ciliogenesis assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mutagenesis of ubiquitylation sites combined with E3 ligase identification and functional ciliogenesis rescue assays\",\n      \"pmids\": [\"25270598\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Soluble decorin induces mitophagy in breast carcinoma cells through a pathway involving PGC-1α and mitostatin (TpMs/TCHP). PGC-1α binds MITOSTATIN mRNA to stabilize it, increasing mitostatin protein levels. Depletion of mitostatin blocks decorin-evoked or rapamycin-evoked mitophagy and increases VEGFA production, establishing mitostatin as a key regulator of tumor cell mitophagy and angiostasis downstream of the decorin/Met axis.\",\n      \"method\": \"siRNA knockdown, mRNA stability assays, RIP (RNA immunoprecipitation), mitophagy assays, VEGFA measurement\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods (RIP, KD, functional mitophagy assay) but single lab\",\n      \"pmids\": [\"24403067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Ndel1, a dynein modulator, localizes at the subdistal appendage of the mother centriole and acts as an upstream regulator of the trichoplein (TCHP)–Aurora A pathway. In proliferating cells, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation; this is rescued by forced trichoplein expression or KCTD17 co-knockdown. Serum starvation triggers transient Ndel1 degradation, which precedes trichoplein disappearance and allows ciliogenesis. Forced Ndel1 expression suppresses trichoplein degradation and axoneme extension, mimicking trichoplein overexpression.\",\n      \"method\": \"siRNA knockdown, overexpression rescue, immunofluorescence, in vivo Ndel1-hypomorphic mouse model (kidney tubular epithelia)\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with rescue experiments and in vivo validation in hypomorphic mice\",\n      \"pmids\": [\"26880200\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Silencing of TpMs (TCHP) in cancer cells causes chromosome mis-segregation, DNA damage, and chromosomal instability. TpMs interacts with Mad2, and its depletion results in decreased levels of Mad2 and Cyclin B1 proteins, consistent with defective spindle assembly checkpoint activation and aberrant mitotic progression.\",\n      \"method\": \"siRNA knockdown, chromosome segregation assays, DNA damage markers, co-immunoprecipitation (TpMs–Mad2 interaction), Western blot for Mad2 and Cyclin B1\",\n      \"journal\": \"Cancers\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP for Mad2 interaction plus functional chromosomal instability readouts, single lab\",\n      \"pmids\": [\"32316593\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TpMs (TCHP) depletion causes alterations in the 3D architecture of telomeres and changes the spatial arrangement of chromosomes and other nuclear components in colon cancer HCT116 cells, as revealed by 3D structured illumination microscopy. These nuclear architecture changes are consistent with the chromosomal instability phenotype and connect TpMs tumor suppressor function to maintenance of proper telomere and nuclear organization.\",\n      \"method\": \"3D structured illumination microscopy (3D-SIM), 3D imaging of telomere architecture in TpMs-depleted cells\",\n      \"journal\": \"Biomedicines\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single method (super-resolution microscopy) with localization/structural readout, single lab\",\n      \"pmids\": [\"35884905\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TCHP (trichoplein) is markedly upregulated in hepatocellular carcinoma. Mechanistically, TCHP localizes to centrosomes and promotes liquid-liquid phase separation (LLPS)-driven condensate formation with Aurora A kinase (AURKA), thereby enhancing AURKA activation and safeguarding mitotic fidelity. TCHP overexpression accelerates hepatocarcinogenesis in mice, while its depletion suppresses tumor growth by inducing mitotic defects. TCHP inhibition also sensitizes liver cancer cells to the AURKA inhibitor alisertib, defining a TCHP–AURKA oncogenic axis.\",\n      \"method\": \"Mouse hepatocarcinogenesis overexpression model, siRNA/shRNA depletion, LLPS condensate assays, co-localization at centrosomes, AURKA activity assays, drug synergy with alisertib\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo mouse model plus LLPS mechanistic assays plus AURKA activity readout and pharmacological validation\",\n      \"pmids\": [\"42034602\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TCHP (trichoplein/mitostatin) is a centrosomal scaffold protein that suppresses primary ciliogenesis in proliferating cells by activating Aurora A kinase (a function terminated by CRL3-KCTD17-mediated ubiquitination and proteasomal degradation of TCHP); it anchors microtubules at the centrosome via a complex with Odf2 and ninein, regulates ER-mitochondria tethering and mitophagy in a Mfn2-dependent manner, maintains chromosomal stability through interaction with the spindle assembly checkpoint protein Mad2, and in cancer can drive oncogenesis by forming LLPS condensates with AURKA at centrosomes to enhance its activation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TCHP (Trichoplein/TpMs) is a centrosomal protein that safeguards mitotic fidelity through at least two mechanisms: it interacts with the spindle assembly checkpoint protein Mad2 to maintain checkpoint function, and it promotes AURKA activation by driving liquid-liquid phase separation (LLPS)-dependent condensate formation at centrosomes [PMID:32316593, PMID:42034602]. Depletion of TCHP causes chromosome mis-segregation, DNA damage, chromosomal instability, and alterations in telomere and nuclear 3D architecture [PMID:32316593, PMID:35884905]. In a mouse hepatocarcinogenesis model, TCHP overexpression accelerates tumor development while its depletion suppresses tumor growth by inducing mitotic defects, indicating context-dependent roles in tumorigenesis [PMID:42034602].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether TCHP contributes to mitotic fidelity was unknown; knockdown revealed that TCHP is required for proper chromosome segregation and spindle assembly checkpoint function through interaction with Mad2.\",\n      \"evidence\": \"siRNA knockdown in cancer cells with co-immunoprecipitation of TpMs–Mad2, immunoblotting for Mad2 and Cyclin B1, and mitotic phenotype analysis\",\n      \"pmids\": [\"32316593\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mad2 interaction mapped by Co-IP only; no reciprocal pulldown or domain mapping reported\",\n        \"Whether TCHP regulates Mad2 protein levels directly or indirectly is unresolved\",\n        \"Mechanism linking TCHP loss to DNA damage is not defined\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Whether TCHP loss affects higher-order nuclear organization was unknown; 3D imaging showed that TCHP depletion alters telomere architecture and spatial chromosome arrangement, extending its role beyond mitotic checkpoint regulation.\",\n      \"evidence\": \"3D structured illumination microscopy (3D-SIM) of TCHP-depleted HCT116 colon cancer cells\",\n      \"pmids\": [\"35884905\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single imaging approach in one cell line without mechanistic explanation for how TCHP influences telomere architecture\",\n        \"No functional consequence of altered telomere architecture was demonstrated\",\n        \"Relationship between telomere defects and the chromosome mis-segregation phenotype is not established\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"How TCHP mechanistically operates at centrosomes was unclear; LLPS condensate assays demonstrated that TCHP promotes phase separation-driven AURKA condensate formation, providing a biophysical mechanism for AURKA activation and linking TCHP to centrosome-based mitotic control.\",\n      \"evidence\": \"In vivo mouse hepatocarcinogenesis model, TCHP overexpression/depletion functional assays, LLPS condensate assay with AURKA, centrosome co-localization imaging\",\n      \"pmids\": [\"42034602\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; LLPS-driven AURKA activation awaits independent replication\",\n        \"Whether TCHP's AURKA-activating and Mad2-interacting functions are coordinated or independent is unknown\",\n        \"Structural determinants of TCHP that drive phase separation are not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The integration of TCHP's checkpoint (Mad2) and centrosomal (AURKA LLPS) functions into a unified mechanistic model remains unresolved, and the structural basis for TCHP's phase separation activity and its direct versus indirect effects on telomere architecture are open questions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structure or domain-resolution mapping of TCHP interactions with Mad2 or AURKA\",\n        \"Context-dependent tumor-promoting versus tumor-suppressing roles are not mechanistically reconciled\",\n        \"Whether TCHP functions in non-cancer cell types or during normal development is unexplored in the primary literature\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MAD2L1\", \"AURKA\"],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"TCHP (trichoplein) is a centrosome-associated scaffold protein that coordinates ciliogenesis, microtubule organization, mitochondrial dynamics, and mitotic fidelity. At the subdistal-to-medial zone of centrioles, TCHP forms a complex with Odf2 and ninein to anchor microtubules and activates Aurora A kinase to suppress primary cilium formation in proliferating cells; CRL3-KCTD17-mediated ubiquitination and proteasomal degradation of TCHP at K50/K57 terminates this suppression, permitting axoneme extension during ciliogenesis [PMID:21325031, PMID:25270598, PMID:26880200]. TCHP also localizes to ER–mitochondria contact sites where it regulates mitochondrial morphology and tethering in an Mfn2-dependent manner, functioning as a downstream effector of decorin-evoked mitophagy [PMID:20930847, PMID:24403067]. In cancer, TCHP interacts with Mad2 to support spindle assembly checkpoint function and chromosomal stability, and when overexpressed drives oncogenesis through liquid–liquid phase separation condensates with AURKA at centrosomes that enhance AURKA activation [PMID:32316593, PMID:42034602].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"The first mechanistic insight into TCHP revealed an unexpected non-centrosomal role: TCHP resides at ER–mitochondria contact sites and modulates their tethering and mitochondrial fission through Mfn2, establishing it as a regulator of organelle communication and Ca2+-dependent apoptosis.\",\n      \"evidence\": \"Subcellular fractionation, immunostaining, genetic knockdown/overexpression, and Mfn2 epistasis in mammalian cells\",\n      \"pmids\": [\"20930847\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct binding interface between TCHP and Mfn2 not mapped\",\n        \"Whether ER–mitochondria tethering function operates independently of centrosomal roles is unknown\",\n        \"In vivo validation of the ER–mitochondria phenotype not performed\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Establishing TCHP's centrosomal function, direct binding to Odf2 and ninein was demonstrated, placing TCHP in a hierarchical complex (Odf2 → TCHP → ninein) required for microtubule anchoring at the centrosome.\",\n      \"evidence\": \"Co-immunoprecipitation, reciprocal siRNA depletion epistasis, and functional MT-anchoring assays\",\n      \"pmids\": [\"21325031\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the Odf2–TCHP–ninein interaction not resolved\",\n        \"Whether TCHP's MT-anchoring role is cell-type specific remains untested\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Two independent studies resolved how TCHP is removed to permit ciliogenesis and linked TCHP to mitophagy: CRL3-KCTD17 ubiquitinates TCHP at K50/K57 to trigger its proteasomal degradation and inactivate Aurora A, initiating axoneme extension; separately, PGC-1α stabilizes TCHP mRNA to increase its protein levels, which are required for decorin-evoked mitophagy and suppression of VEGFA.\",\n      \"evidence\": \"Global E3 screen with non-ubiquitylatable K50/57R mutant and ciliogenesis rescue (ciliogenesis); RIP, siRNA, mitophagy and VEGFA assays in breast carcinoma cells (mitophagy)\",\n      \"pmids\": [\"25270598\", \"24403067\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether TCHP directly activates Aurora A or acts through an intermediary scaffold is not fully defined\",\n        \"Mitophagy function of TCHP established only in breast carcinoma cells by a single lab\",\n        \"Relationship between TCHP's ciliogenesis-suppressive and mitophagy-promoting functions not clarified\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Ndel1 was placed upstream of TCHP in the ciliogenesis pathway: serum starvation triggers transient Ndel1 degradation, which precedes TCHP loss from the mother centriole, establishing a temporal cascade (Ndel1 → TCHP → Aurora A) that gates ciliogenesis initiation.\",\n      \"evidence\": \"siRNA epistasis with rescue, immunofluorescence, and in vivo validation in Ndel1-hypomorphic mouse kidneys\",\n      \"pmids\": [\"26880200\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How Ndel1 physically stabilizes TCHP at the mother centriole is not determined\",\n        \"Whether Ndel1-TCHP epistasis operates in tissues beyond kidney tubular epithelium is unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"TCHP was linked to mitotic fidelity: its depletion causes chromosome mis-segregation and DNA damage, and it interacts with the spindle assembly checkpoint protein Mad2, with loss reducing Mad2 and Cyclin B1 levels.\",\n      \"evidence\": \"Co-immunoprecipitation, siRNA depletion, chromosome segregation assays and DNA damage markers in cancer cells\",\n      \"pmids\": [\"32316593\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mad2 interaction demonstrated by a single Co-IP without reciprocal pull-down or structural validation\",\n        \"Whether TCHP regulates Mad2 stability versus localization is not distinguished\",\n        \"Unclear whether chromosomal instability arises from SAC defects or from centrosomal/MT-anchoring dysfunction\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Super-resolution imaging extended the chromosomal instability phenotype by showing that TCHP depletion alters 3D telomere architecture and nuclear organization, connecting its function to higher-order genome maintenance.\",\n      \"evidence\": \"3D structured illumination microscopy in TCHP-depleted HCT116 cells\",\n      \"pmids\": [\"35884905\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single imaging method without independent functional confirmation of telomere dysfunction\",\n        \"Whether telomere architectural changes are a direct consequence of TCHP loss or secondary to chromosomal instability is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"In hepatocellular carcinoma, TCHP was shown to form LLPS condensates with AURKA at centrosomes, enhancing AURKA activation and promoting oncogenesis; TCHP overexpression accelerated hepatocarcinogenesis in mice, and its inhibition synergized with the AURKA inhibitor alisertib.\",\n      \"evidence\": \"Mouse overexpression hepatocarcinogenesis model, LLPS condensate assays, AURKA activity readouts, and alisertib drug synergy\",\n      \"pmids\": [\"42034602\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"LLPS condensate composition beyond TCHP–AURKA not characterized\",\n        \"Whether LLPS-mediated AURKA activation is relevant in non-cancerous proliferating cells is unknown\",\n        \"Structural determinants of TCHP phase separation not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how TCHP's centrosomal, ER–mitochondria, and SAC-related functions are coordinated—whether distinct pools of TCHP operate at different subcellular sites and how they are partitioned in different cell states.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No study has simultaneously tracked TCHP pools at centrosomes, ER–mitochondria contacts, and the spindle\",\n        \"Post-translational modification map beyond K50/K57 ubiquitination is incomplete\",\n        \"No structural model of TCHP exists\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 2, 4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1, 2, 4, 7]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 2, 4]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"complexes\": [\n      \"Odf2–trichoplein–ninein centrosomal complex\"\n    ],\n    \"partners\": [\n      \"ODF2\",\n      \"NIN\",\n      \"AURKA\",\n      \"KCTD17\",\n      \"NDEL1\",\n      \"MFN2\",\n      \"MAD2L1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}