{"gene":"TRAPPC14","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2019,"finding":"TRAPPC14 (C7orf43/MAP11) directly binds to Rabin8 (a Rab8 GEF) and its knockdown diminishes Rabin8 preciliary centrosome accumulation, establishing a role in preciliary vesicle trafficking during ciliogenesis.","method":"MS-based interactome screen, co-sedimentation, direct binding assay, knockdown with centrosome accumulation readout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (MS identification, direct binding assay, co-sedimentation, knockdown phenotype) in a single rigorous study","pmids":["31467083"],"is_preprint":false},{"year":2019,"finding":"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific component that co-sediments with TRAPPII subunits and directly interacts with TRAPPC proteins, but is dispensable for TRAPPII complex integrity while mediating Rabin8 association with TRAPPII.","method":"Co-sedimentation, direct protein interaction assays, knockdown/reconstitution","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct binding demonstrated, co-sedimentation, and functional dispensability tested with multiple orthogonal methods in a single study","pmids":["31467083"],"is_preprint":false},{"year":2019,"finding":"TRAPPC14 interacts with distal appendage proteins FBF1 and CEP83, which are required for GFP-Rabin8 centrosomal accumulation, supporting a role for TRAPPII in tethering preciliary vesicles to the mother centriole.","method":"Co-immunoprecipitation, knockdown with fluorescence-based centrosome accumulation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction shown and functional consequence of FBF1/CEP83 knockdown on Rabin8 accumulation demonstrated, single lab","pmids":["31467083"],"is_preprint":false},{"year":2019,"finding":"TRAPPC14 (MAP11/C7orf43) associates with mitotic spindles, co-localizing and physically associating with α-tubulin during mitosis, and MAP11 expression precedes α-tubulin in gap formation of cell abscission at the midbody, implicating a role in spindle dynamics and cytokinesis.","method":"Immunofluorescence, co-immunoprecipitation in SH-SY5Y cells","journal":"Brain : a journal of neurology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — co-IP plus immunofluorescence co-localization, single lab, two orthogonal methods","pmids":["30715179"],"is_preprint":false},{"year":2019,"finding":"MAP11 (TRAPPC14) co-localizes with PLK1 at the edges of microtubule extensions of daughter cells post-cytokinesis abscission, suggesting a role in cell abscission regulation.","method":"Immunofluorescence in SH-SY5Y cells","journal":"Brain : a journal of neurology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single method (immunofluorescence co-localization only), no functional validation of the PLK1 interaction","pmids":["30715179"],"is_preprint":false},{"year":2019,"finding":"Lentiviral-mediated silencing of MAP11 (TRAPPC14) diminished SH-SY5Y cell viability by reducing proliferation rather than affecting apoptosis, and CRISPR/Cas9 knockout of the MAP11 orthologue in zebrafish caused microcephaly with decreased neuronal proliferation.","method":"Lentiviral shRNA knockdown with proliferation/apoptosis assays; CRISPR/Cas9 knockout in zebrafish","journal":"Brain : a journal of neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function in two systems (human cells and zebrafish) with defined cellular phenotype, single lab","pmids":["30715179"],"is_preprint":false},{"year":2019,"finding":"C7orf43 (TRAPPC14) upregulates TERT expression through Yes-associated protein 1 (YAP1), with its responsive site mapped to the region between base pairs -169 and -59 in the TERT promoter.","method":"Genome-wide shRNA screen, promoter assay","journal":"Cancer science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — promoter assay and shRNA screen, single lab, limited mechanistic depth on YAP1 connection","pmids":["30447097"],"is_preprint":false}],"current_model":"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific subunit that directly binds Rabin8 to mediate its preciliary centrosome recruitment and ciliogenesis, interacts with distal appendage proteins FBF1 and CEP83 to tether preciliary vesicles at the mother centriole, and also functions as a microtubule-associated protein that associates with α-tubulin and PLK1 during mitosis and cytokinesis, with loss-of-function causing reduced cell proliferation and microcephaly."},"narrative":{"mechanistic_narrative":"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific subunit that links the multisubunit tethering complex to the early steps of ciliogenesis [PMID:31467083]. It directly binds Rabin8, a Rab8 GEF, and is required for Rabin8 accumulation at the preciliary centrosome, thereby coupling TRAPPII to preciliary vesicle trafficking; although it mediates Rabin8 association with TRAPPII, it is itself dispensable for TRAPPII complex integrity [PMID:31467083]. TRAPPC14 also engages the distal appendage proteins FBF1 and CEP83, which are themselves needed for Rabin8 centrosomal accumulation, consistent with TRAPPII tethering preciliary vesicles to the mother centriole [PMID:31467083]. Independently, TRAPPC14 associates with mitotic spindles and physically interacts with α-tubulin during mitosis, with its expression preceding α-tubulin at sites of midbody gap formation during abscission, implicating it in spindle dynamics and cytokinesis [PMID:30715179]. Loss of TRAPPC14 reduces cell proliferation without inducing apoptosis in human cells and produces microcephaly with decreased neuronal proliferation in zebrafish [PMID:30715179].","teleology":[{"year":2019,"claim":"Established TRAPPC14 as a dedicated TRAPPII-complex subunit that couples the tethering complex to the ciliogenesis machinery rather than to general complex assembly.","evidence":"Co-sedimentation, direct protein interaction assays, and knockdown/reconstitution showing TRAPPII association but dispensability for complex integrity","pmids":["31467083"],"confidence":"High","gaps":["Structural basis of TRAPPC14 integration into TRAPPII not resolved","Whether TRAPPC14 modulates TRAPPII GEF activity is unknown"]},{"year":2019,"claim":"Identified the direct Rabin8 interaction and its functional requirement, defining how TRAPPC14 routes a Rab8 GEF to the preciliary centrosome.","evidence":"MS-based interactome screen, direct binding assay, co-sedimentation, and knockdown with centrosome accumulation readout","pmids":["31467083"],"confidence":"High","gaps":["Binding interface on Rabin8 not mapped","Downstream effect on Rab8 activation not directly measured"]},{"year":2019,"claim":"Connected TRAPPC14/TRAPPII to mother-centriole distal appendages, providing a tethering mechanism for preciliary vesicle docking.","evidence":"Co-immunoprecipitation with FBF1/CEP83 and knockdown with fluorescence-based centrosome accumulation assay","pmids":["31467083"],"confidence":"Medium","gaps":["Direct versus indirect nature of FBF1/CEP83 binding not resolved","Order of recruitment relative to Rabin8 not established"]},{"year":2019,"claim":"Revealed a ciliogenesis-independent role at the mitotic spindle and midbody, suggesting TRAPPC14 acts as a microtubule-associated protein during cell division.","evidence":"Immunofluorescence co-localization and co-immunoprecipitation with α-tubulin in SH-SY5Y cells","pmids":["30715179"],"confidence":"Medium","gaps":["Whether α-tubulin binding is direct is unclear","Functional requirement for spindle/midbody dynamics not tested by perturbation"]},{"year":2019,"claim":"Linked TRAPPC14 loss to a proliferation defect and microcephaly, establishing physiological relevance for neurodevelopment.","evidence":"Lentiviral shRNA knockdown with proliferation/apoptosis assays in human cells and CRISPR/Cas9 knockout in zebrafish","pmids":["30715179"],"confidence":"Medium","gaps":["Causal mutation in human microcephaly patients not described here","Mechanism connecting proliferation loss to ciliary versus mitotic functions unresolved"]},{"year":2019,"claim":"Proposed a transcriptional link to TERT expression via YAP1, hinting at a role in proliferative/telomere regulation.","evidence":"Genome-wide shRNA screen and TERT promoter assay mapping a responsive site","pmids":["30447097"],"confidence":"Low","gaps":["Single lab, limited mechanistic depth on the YAP1 connection","Direct molecular link between TRAPPC14 and the TERT promoter not demonstrated","Relationship to ciliary or mitotic functions unknown"]},{"year":null,"claim":"How TRAPPC14's roles in preciliary vesicle tethering and mitotic spindle/cytokinesis are mechanistically coordinated, and whether either underlies the proliferation/microcephaly phenotype, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of TRAPPC14 within TRAPPII","PLK1 functional interaction not validated","No reconstitution of the tethering step"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[3]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3]}],"complexes":["TRAPPII"],"partners":["RAB3IP","FBF1","CEP83","TUBA1A","PLK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WVR3","full_name":"Trafficking protein particle complex subunit 14","aliases":["Microtubule-associated protein 11"],"length_aa":580,"mass_kda":62.6,"function":"Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether (PubMed:30715179, PubMed:31467083). TRAPP II complex also has GEF activity toward RAB1A (By similarity). TRAPPC14 is dispensable for TRAPPII complex integrity but mediates RAB3IP preciliary vesicle trafficking to the mother centriole during ciliogenesis (PubMed:31467083). Modulates YAP1 activity as transcriptional regulator (PubMed:30447097)","subcellular_location":"Cytoplasm, cytoskeleton, spindle; Vesicle; Midbody; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q8WVR3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TRAPPC14","classification":"Not Classified","n_dependent_lines":10,"n_total_lines":1208,"dependency_fraction":0.008278145695364239},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TRAPPC14","total_profiled":1310},"omim":[{"mim_id":"618351","title":"MICROCEPHALY 25, PRIMARY, AUTOSOMAL RECESSIVE; MCPH25","url":"https://www.omim.org/entry/618351"},{"mim_id":"618350","title":"TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 14; TRAPPC14","url":"https://www.omim.org/entry/618350"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Vesicles","reliability":"Enhanced"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Centriolar satellite","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TRAPPC14"},"hgnc":{"alias_symbol":["FLJ10925"],"prev_symbol":["C7orf43","MAP11"]},"alphafold":{"accession":"Q8WVR3","domains":[{"cath_id":"2.60.40.10","chopping":"6-56_71-91_134-221","consensus_level":"high","plddt":79.3482,"start":6,"end":221},{"cath_id":"2.60.40,2.60.40","chopping":"225-366","consensus_level":"high","plddt":79.2809,"start":225,"end":366},{"cath_id":"2.60.40.10","chopping":"371-479_564-577","consensus_level":"high","plddt":81.5041,"start":371,"end":577}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WVR3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WVR3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WVR3-F1-predicted_aligned_error_v6.png","plddt_mean":70.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TRAPPC14","jax_strain_url":"https://www.jax.org/strain/search?query=TRAPPC14"},"sequence":{"accession":"Q8WVR3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WVR3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WVR3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WVR3"}},"corpus_meta":[{"pmid":"30715179","id":"PMC_30715179","title":"Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish.","date":"2019","source":"Brain : a journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/30715179","citation_count":33,"is_preprint":false},{"pmid":"15087135","id":"PMC_15087135","title":"Characterization of a major outer membrane protein multigene family in Ehrlichia ruminantium.","date":"2004","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/15087135","citation_count":32,"is_preprint":false},{"pmid":"15995193","id":"PMC_15995193","title":"Transcription analysis of the major antigenic protein 1 multigene family of three in vitro-cultured Ehrlichia ruminantium isolates.","date":"2005","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/15995193","citation_count":30,"is_preprint":false},{"pmid":"12039046","id":"PMC_12039046","title":"Transcriptional analysis of the major antigenic protein 1 multigene family of Cowdria ruminantium.","date":"2002","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/12039046","citation_count":27,"is_preprint":false},{"pmid":"31467083","id":"PMC_31467083","title":"The C7orf43/TRAPPC14 component links the TRAPPII complex to Rabin8 for preciliary vesicle tethering at the mother centriole during ciliogenesis.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31467083","citation_count":25,"is_preprint":false},{"pmid":"30447097","id":"PMC_30447097","title":"Identification of genes involved in the regulation of TERT in hepatocellular carcinoma.","date":"2019","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/30447097","citation_count":18,"is_preprint":false},{"pmid":"17321077","id":"PMC_17321077","title":"Differential transcription of the major antigenic protein 1 multigene family of Ehrlichia ruminantium in Amblyomma variegatum ticks.","date":"2007","source":"Veterinary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/17321077","citation_count":17,"is_preprint":false},{"pmid":"12381577","id":"PMC_12381577","title":"Major outer membrane proteins of Ehrlichia ruminantium encoded by a multigene family.","date":"2002","source":"Annals of the New York Academy of Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/12381577","citation_count":3,"is_preprint":false},{"pmid":"38138609","id":"PMC_38138609","title":"Exploring Thiazolopyridine AV25R: Unraveling of Biological Activities, Selective Anti-Cancer Properties and In Silico Target and Binding Prediction in Hematological Neoplasms.","date":"2023","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38138609","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6717,"output_tokens":1594,"usd":0.022031,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8354,"output_tokens":2300,"usd":0.049635,"stage2_stop_reason":"end_turn"},"total_usd":0.071666,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"TRAPPC14 (C7orf43/MAP11) directly binds to Rabin8 (a Rab8 GEF) and its knockdown diminishes Rabin8 preciliary centrosome accumulation, establishing a role in preciliary vesicle trafficking during ciliogenesis.\",\n      \"method\": \"MS-based interactome screen, co-sedimentation, direct binding assay, knockdown with centrosome accumulation readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (MS identification, direct binding assay, co-sedimentation, knockdown phenotype) in a single rigorous study\",\n      \"pmids\": [\"31467083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific component that co-sediments with TRAPPII subunits and directly interacts with TRAPPC proteins, but is dispensable for TRAPPII complex integrity while mediating Rabin8 association with TRAPPII.\",\n      \"method\": \"Co-sedimentation, direct protein interaction assays, knockdown/reconstitution\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct binding demonstrated, co-sedimentation, and functional dispensability tested with multiple orthogonal methods in a single study\",\n      \"pmids\": [\"31467083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRAPPC14 interacts with distal appendage proteins FBF1 and CEP83, which are required for GFP-Rabin8 centrosomal accumulation, supporting a role for TRAPPII in tethering preciliary vesicles to the mother centriole.\",\n      \"method\": \"Co-immunoprecipitation, knockdown with fluorescence-based centrosome accumulation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction shown and functional consequence of FBF1/CEP83 knockdown on Rabin8 accumulation demonstrated, single lab\",\n      \"pmids\": [\"31467083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"TRAPPC14 (MAP11/C7orf43) associates with mitotic spindles, co-localizing and physically associating with α-tubulin during mitosis, and MAP11 expression precedes α-tubulin in gap formation of cell abscission at the midbody, implicating a role in spindle dynamics and cytokinesis.\",\n      \"method\": \"Immunofluorescence, co-immunoprecipitation in SH-SY5Y cells\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — co-IP plus immunofluorescence co-localization, single lab, two orthogonal methods\",\n      \"pmids\": [\"30715179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MAP11 (TRAPPC14) co-localizes with PLK1 at the edges of microtubule extensions of daughter cells post-cytokinesis abscission, suggesting a role in cell abscission regulation.\",\n      \"method\": \"Immunofluorescence in SH-SY5Y cells\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single method (immunofluorescence co-localization only), no functional validation of the PLK1 interaction\",\n      \"pmids\": [\"30715179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Lentiviral-mediated silencing of MAP11 (TRAPPC14) diminished SH-SY5Y cell viability by reducing proliferation rather than affecting apoptosis, and CRISPR/Cas9 knockout of the MAP11 orthologue in zebrafish caused microcephaly with decreased neuronal proliferation.\",\n      \"method\": \"Lentiviral shRNA knockdown with proliferation/apoptosis assays; CRISPR/Cas9 knockout in zebrafish\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in two systems (human cells and zebrafish) with defined cellular phenotype, single lab\",\n      \"pmids\": [\"30715179\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"C7orf43 (TRAPPC14) upregulates TERT expression through Yes-associated protein 1 (YAP1), with its responsive site mapped to the region between base pairs -169 and -59 in the TERT promoter.\",\n      \"method\": \"Genome-wide shRNA screen, promoter assay\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — promoter assay and shRNA screen, single lab, limited mechanistic depth on YAP1 connection\",\n      \"pmids\": [\"30447097\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific subunit that directly binds Rabin8 to mediate its preciliary centrosome recruitment and ciliogenesis, interacts with distal appendage proteins FBF1 and CEP83 to tether preciliary vesicles at the mother centriole, and also functions as a microtubule-associated protein that associates with α-tubulin and PLK1 during mitosis and cytokinesis, with loss-of-function causing reduced cell proliferation and microcephaly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TRAPPC14 (C7orf43/MAP11) is a TRAPPII complex-specific subunit that links the multisubunit tethering complex to the early steps of ciliogenesis [#1]. It directly binds Rabin8, a Rab8 GEF, and is required for Rabin8 accumulation at the preciliary centrosome, thereby coupling TRAPPII to preciliary vesicle trafficking; although it mediates Rabin8 association with TRAPPII, it is itself dispensable for TRAPPII complex integrity [#0, #1]. TRAPPC14 also engages the distal appendage proteins FBF1 and CEP83, which are themselves needed for Rabin8 centrosomal accumulation, consistent with TRAPPII tethering preciliary vesicles to the mother centriole [#2]. Independently, TRAPPC14 associates with mitotic spindles and physically interacts with \\u03b1-tubulin during mitosis, with its expression preceding \\u03b1-tubulin at sites of midbody gap formation during abscission, implicating it in spindle dynamics and cytokinesis [#3]. Loss of TRAPPC14 reduces cell proliferation without inducing apoptosis in human cells and produces microcephaly with decreased neuronal proliferation in zebrafish [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Established TRAPPC14 as a dedicated TRAPPII-complex subunit that couples the tethering complex to the ciliogenesis machinery rather than to general complex assembly.\",\n      \"evidence\": \"Co-sedimentation, direct protein interaction assays, and knockdown/reconstitution showing TRAPPII association but dispensability for complex integrity\",\n      \"pmids\": [\"31467083\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of TRAPPC14 integration into TRAPPII not resolved\", \"Whether TRAPPC14 modulates TRAPPII GEF activity is unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Identified the direct Rabin8 interaction and its functional requirement, defining how TRAPPC14 routes a Rab8 GEF to the preciliary centrosome.\",\n      \"evidence\": \"MS-based interactome screen, direct binding assay, co-sedimentation, and knockdown with centrosome accumulation readout\",\n      \"pmids\": [\"31467083\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding interface on Rabin8 not mapped\", \"Downstream effect on Rab8 activation not directly measured\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected TRAPPC14/TRAPPII to mother-centriole distal appendages, providing a tethering mechanism for preciliary vesicle docking.\",\n      \"evidence\": \"Co-immunoprecipitation with FBF1/CEP83 and knockdown with fluorescence-based centrosome accumulation assay\",\n      \"pmids\": [\"31467083\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect nature of FBF1/CEP83 binding not resolved\", \"Order of recruitment relative to Rabin8 not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a ciliogenesis-independent role at the mitotic spindle and midbody, suggesting TRAPPC14 acts as a microtubule-associated protein during cell division.\",\n      \"evidence\": \"Immunofluorescence co-localization and co-immunoprecipitation with \\u03b1-tubulin in SH-SY5Y cells\",\n      \"pmids\": [\"30715179\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether \\u03b1-tubulin binding is direct is unclear\", \"Functional requirement for spindle/midbody dynamics not tested by perturbation\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked TRAPPC14 loss to a proliferation defect and microcephaly, establishing physiological relevance for neurodevelopment.\",\n      \"evidence\": \"Lentiviral shRNA knockdown with proliferation/apoptosis assays in human cells and CRISPR/Cas9 knockout in zebrafish\",\n      \"pmids\": [\"30715179\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal mutation in human microcephaly patients not described here\", \"Mechanism connecting proliferation loss to ciliary versus mitotic functions unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Proposed a transcriptional link to TERT expression via YAP1, hinting at a role in proliferative/telomere regulation.\",\n      \"evidence\": \"Genome-wide shRNA screen and TERT promoter assay mapping a responsive site\",\n      \"pmids\": [\"30447097\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single lab, limited mechanistic depth on the YAP1 connection\", \"Direct molecular link between TRAPPC14 and the TERT promoter not demonstrated\", \"Relationship to ciliary or mitotic functions unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TRAPPC14's roles in preciliary vesicle tethering and mitotic spindle/cytokinesis are mechanistically coordinated, and whether either underlies the proliferation/microcephaly phenotype, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of TRAPPC14 within TRAPPII\", \"PLK1 functional interaction not validated\", \"No reconstitution of the tethering step\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\"TRAPPII\"],\n    \"partners\": [\"RAB3IP\", \"FBF1\", \"CEP83\", \"TUBA1A\", \"PLK1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}