{"gene":"ANKRD10","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":2025,"finding":"RBPMS depletion in bladder cancer cells causes alternative splicing of ANKRD10, increasing expression of the ANKRD10-2 isoform, which functions as a transcriptional co-activator of MYC proteins to augment their transcriptional activity and promote cell migration/invasion.","method":"RNA-Seq identification of ANKRD10 as RBPMS target; knockdown of RBPMS and ANKRD10-2 in bladder cancer cells with migration/invasion readout; co-activator activity assay for MYC transcriptional activity","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — functional knockdown experiments with defined cellular phenotype and pathway placement (MYC co-activation), multiple orthogonal methods (RNA-Seq, KD rescue, transcriptional activity assay), single lab","pmids":["40044952"],"is_preprint":false}],"current_model":"ANKRD10-2, an alternative splice isoform of ANKRD10 generated upon loss of the RNA-binding protein RBPMS, acts as a transcriptional co-activator of MYC proteins to enhance MYC transcriptional activity and promote bladder cancer cell migration and invasion."},"narrative":{"mechanistic_narrative":"ANKRD10 is regulated at the level of alternative splicing by the RNA-binding protein RBPMS, and its splice isoform ANKRD10-2 functions as a transcriptional co-activator of MYC in bladder cancer [PMID:40044952]. Depletion of RBPMS shifts splicing toward the ANKRD10-2 isoform, which augments MYC transcriptional activity and drives cancer cell migration and invasion [PMID:40044952]. Beyond this RBPMS–ANKRD10-2–MYC axis, no further mechanistic detail for ANKRD10 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Established that ANKRD10 is a splicing target of RBPMS and that its ANKRD10-2 isoform acts as a MYC co-activator promoting bladder cancer invasiveness, placing ANKRD10 downstream of an RNA-binding regulator and upstream of MYC-driven transcription.","evidence":"RNA-Seq identification of ANKRD10 as an RBPMS splicing target, with RBPMS and ANKRD10-2 knockdown plus migration/invasion and MYC transcriptional activity assays in bladder cancer cells","pmids":["40044952"],"confidence":"Medium","gaps":["Mechanism by which ANKRD10-2 physically co-activates MYC (direct binding vs. indirect) is not defined","No structural or domain-level basis for isoform-specific co-activator activity","Findings from a single lab and limited to bladder cancer context"]},{"year":null,"claim":"Whether ANKRD10 has functions outside the RBPMS–MYC axis, and the molecular activity and localization of its protein product, remain unknown.","evidence":"No further direct evidence in the available corpus","pmids":[],"confidence":"Medium","gaps":["No biochemical characterization of ANKRD10 protein interactions or domains","No subcellular localization data","No evidence in tissues or cancers other than bladder"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0]}],"complexes":[],"partners":["MYC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NXR5","full_name":"Ankyrin repeat domain-containing protein 10","aliases":[],"length_aa":420,"mass_kda":44.8,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9NXR5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANKRD10","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000088448","cell_line_id":"CID001384","localizations":[{"compartment":"nucleoplasm","grade":3}],"interactors":[{"gene":"TAB2","stoichiometry":0.2},{"gene":"TRIP6","stoichiometry":0.2},{"gene":"GAPDH","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001384","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ANKRD10"},"hgnc":{"alias_symbol":["FLJ20093"],"prev_symbol":[]},"alphafold":{"accession":"Q9NXR5","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXR5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXR5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NXR5-F1-predicted_aligned_error_v6.png","plddt_mean":63.66},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANKRD10","jax_strain_url":"https://www.jax.org/strain/search?query=ANKRD10"},"sequence":{"accession":"Q9NXR5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NXR5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NXR5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NXR5"}},"corpus_meta":[{"pmid":"40044952","id":"PMC_40044952","title":"RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10.","date":"2025","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/40044952","citation_count":7,"is_preprint":false},{"pmid":"40969342","id":"PMC_40969342","title":"A comprehensive analysis of allele-specific expression and transcriptomic profiling in pig limbic and endocrine tissues.","date":"2025","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/40969342","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3345,"output_tokens":353,"usd":0.007665,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6599,"output_tokens":913,"usd":0.02791,"stage2_stop_reason":"end_turn"},"total_usd":0.035575,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"RBPMS depletion in bladder cancer cells causes alternative splicing of ANKRD10, increasing expression of the ANKRD10-2 isoform, which functions as a transcriptional co-activator of MYC proteins to augment their transcriptional activity and promote cell migration/invasion.\",\n      \"method\": \"RNA-Seq identification of ANKRD10 as RBPMS target; knockdown of RBPMS and ANKRD10-2 in bladder cancer cells with migration/invasion readout; co-activator activity assay for MYC transcriptional activity\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — functional knockdown experiments with defined cellular phenotype and pathway placement (MYC co-activation), multiple orthogonal methods (RNA-Seq, KD rescue, transcriptional activity assay), single lab\",\n      \"pmids\": [\"40044952\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKRD10-2, an alternative splice isoform of ANKRD10 generated upon loss of the RNA-binding protein RBPMS, acts as a transcriptional co-activator of MYC proteins to enhance MYC transcriptional activity and promote bladder cancer cell migration and invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANKRD10 is regulated at the level of alternative splicing by the RNA-binding protein RBPMS, and its splice isoform ANKRD10-2 functions as a transcriptional co-activator of MYC in bladder cancer [#0]. Depletion of RBPMS shifts splicing toward the ANKRD10-2 isoform, which augments MYC transcriptional activity and drives cancer cell migration and invasion [#0]. Beyond this RBPMS–ANKRD10-2–MYC axis, no further mechanistic detail for ANKRD10 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Established that ANKRD10 is a splicing target of RBPMS and that its ANKRD10-2 isoform acts as a MYC co-activator promoting bladder cancer invasiveness, placing ANKRD10 downstream of an RNA-binding regulator and upstream of MYC-driven transcription.\",\n      \"evidence\": \"RNA-Seq identification of ANKRD10 as an RBPMS splicing target, with RBPMS and ANKRD10-2 knockdown plus migration/invasion and MYC transcriptional activity assays in bladder cancer cells\",\n      \"pmids\": [\"40044952\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which ANKRD10-2 physically co-activates MYC (direct binding vs. indirect) is not defined\",\n        \"No structural or domain-level basis for isoform-specific co-activator activity\",\n        \"Findings from a single lab and limited to bladder cancer context\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ANKRD10 has functions outside the RBPMS–MYC axis, and the molecular activity and localization of its protein product, remain unknown.\",\n      \"evidence\": \"No further direct evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical characterization of ANKRD10 protein interactions or domains\",\n        \"No subcellular localization data\",\n        \"No evidence in tissues or cancers other than bladder\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MYC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":2,"faith_pct":100.0}}