{"gene":"KNCN","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2018,"finding":"Kncn knockout mice generated by CRISPR/Cas9 show no hearing loss, intact inner ear and hair cell structure, and no deficit in mechanotransduction (MET) in cochlear outer hair cells, demonstrating that KNCN is not essential for kinocilium-oriented hair bundle development or mechanotransduction in cochlear hair cells.","method":"CRISPR/Cas9 knockout mouse, audiometry, histology, mechanotransduction electrophysiology","journal":"Frontiers in molecular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (audiometry + MET recording + histology), multiple orthogonal readouts in single lab; establishes a negative result (dispensability) with rigorous in vivo methods","pmids":["30254566"],"is_preprint":false}],"current_model":"KNCN (kinocilin) is a protein enriched in inner ear hair cells and reported to localize to the kinocilium, but genetic knockout in mice demonstrates it is dispensable for kinocilium-oriented hair bundle morphogenesis and mechanotransduction in cochlear hair cells; no other mechanistic function has been experimentally established."},"narrative":{"mechanistic_narrative":"KNCN (kinocilin) is a protein enriched in inner ear hair cells whose functional role remains largely uncharacterized. CRISPR/Cas9 knockout mice lack hearing loss and show intact inner ear and hair cell structure with normal mechanotransduction in cochlear outer hair cells, establishing that KNCN is dispensable for kinocilium-oriented hair bundle development and mechanotransduction in cochlear hair cells [PMID:30254566]. Beyond this negative in vivo result, no molecular activity, binding partner, or alternative function has been experimentally established in the available corpus.","teleology":[{"year":2018,"claim":"Whether KNCN is required for hair bundle morphogenesis and hearing was unknown; targeted deletion answered this by showing the gene is dispensable for cochlear hair cell development and function.","evidence":"CRISPR/Cas9 knockout mouse assessed by audiometry, histology, and mechanotransduction electrophysiology","pmids":["30254566"],"confidence":"Medium","gaps":["Does not identify any molecular activity or binding partner of KNCN","Possible functional redundancy or vestibular/non-cochlear roles not excluded","Subcellular localization to the kinocilium not directly tested in this knockout study"]},{"year":null,"claim":"The molecular function, interaction partners, and the biological reason for KNCN enrichment in hair cells remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical activity assigned","No physical partners identified","No phenotype establishing a required cellular role"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A6PVL3","full_name":"Kinocilin","aliases":[],"length_aa":124,"mass_kda":12.8,"function":"May play a role in stabilizing dense microtubular networks or in vesicular trafficking","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/A6PVL3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KNCN","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":[],"url":"https://opencell.sf.czbiohub.org/search/KNCN","total_profiled":1310},"omim":[{"mim_id":"611455","title":"KINOCILIN; KNCN","url":"https://www.omim.org/entry/611455"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"brain","ntpm":1.0}],"url":"https://www.proteinatlas.org/search/KNCN"},"hgnc":{"alias_symbol":["FLJ32011","KINO","L5"],"prev_symbol":[]},"alphafold":{"accession":"A6PVL3","domains":[{"cath_id":"-","chopping":"8-77","consensus_level":"high","plddt":67.0373,"start":8,"end":77}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6PVL3","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6PVL3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6PVL3-F1-predicted_aligned_error_v6.png","plddt_mean":60.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KNCN","jax_strain_url":"https://www.jax.org/strain/search?query=KNCN"},"sequence":{"accession":"A6PVL3","fasta_url":"https://rest.uniprot.org/uniprotkb/A6PVL3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6PVL3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6PVL3"}},"corpus_meta":[{"pmid":"2570780","id":"PMC_2570780","title":"Complete amino acid sequence of an immunomodulatory protein, ling zhi-8 (LZ-8). An immunomodulator from a fungus, Ganoderma lucidium, having similarity to immunoglobulin variable regions.","date":"1989","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2570780","citation_count":76,"is_preprint":false},{"pmid":"28307780","id":"PMC_28307780","title":"The evolution of obligate pollination mutualisms: senita cactus and senita moth.","date":"1998","source":"Oecologia","url":"https://pubmed.ncbi.nlm.nih.gov/28307780","citation_count":75,"is_preprint":false},{"pmid":"9442391","id":"PMC_9442391","title":"Effects of the immunosuppressive drugs CsA and FK506 on intracellular signalling and gene regulation.","date":"1997","source":"Immunobiology","url":"https://pubmed.ncbi.nlm.nih.gov/9442391","citation_count":70,"is_preprint":false},{"pmid":"18757570","id":"PMC_18757570","title":"Multilocus sequence typing and phylogenetic analyses of Pseudomonas aeruginosa Isolates from the ocean.","date":"2008","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/18757570","citation_count":45,"is_preprint":false},{"pmid":"7298660","id":"PMC_7298660","title":"Catabolism of globin-haptoglobin in liver cells after intravenous administration of hemoglobin-haptoglobin to rats.","date":"1981","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7298660","citation_count":43,"is_preprint":false},{"pmid":"15613393","id":"PMC_15613393","title":"PreDs: a server for predicting dsDNA-binding site on protein molecular surfaces.","date":"2004","source":"Bioinformatics (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/15613393","citation_count":37,"is_preprint":false},{"pmid":"12799376","id":"PMC_12799376","title":"Purification and characterization of the MQH2:NO oxidoreductase from the hyperthermophilic archaeon Pyrobaculum aerophilum.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12799376","citation_count":35,"is_preprint":false},{"pmid":"1990000","id":"PMC_1990000","title":"Molecular cloning of a cDNA and a gene encoding an immunomodulatory protein, Ling Zhi-8, from a fungus, Ganoderma lucidum.","date":"1991","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1990000","citation_count":34,"is_preprint":false},{"pmid":"31695612","id":"PMC_31695612","title":"Pterostilbene, An Active Constituent of Blueberries, Suppresses Proliferation Potential of Human Cholangiocarcinoma via Enhancing the Autophagic Flux.","date":"2019","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/31695612","citation_count":29,"is_preprint":false},{"pmid":"18469038","id":"PMC_18469038","title":"HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia.","date":"2008","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/18469038","citation_count":25,"is_preprint":false},{"pmid":"3169364","id":"PMC_3169364","title":"Effect of chronic ethanol treatment under partial catalase inhibition on the activity of enzymes related to peroxide metabolism in rat liver and heart.","date":"1988","source":"The International journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3169364","citation_count":25,"is_preprint":false},{"pmid":"3182780","id":"PMC_3182780","title":"Intrahepatocellular site of the catabolism of heme and globin moiety of hemoglobin-haptoglobin after intravenous administration to rats.","date":"1988","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3182780","citation_count":19,"is_preprint":false},{"pmid":"25639816","id":"PMC_25639816","title":"Characterization of Pterocarpus erinaceus kino extract and its gamma-secretase inhibitory properties.","date":"2015","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/25639816","citation_count":11,"is_preprint":false},{"pmid":"21971749","id":"PMC_21971749","title":"Sampling-based exploration of folded state of a protein under kinematic and geometric constraints.","date":"2011","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/21971749","citation_count":10,"is_preprint":false},{"pmid":"26218073","id":"PMC_26218073","title":"Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs.","date":"2015","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/26218073","citation_count":8,"is_preprint":false},{"pmid":"30254566","id":"PMC_30254566","title":"Deletion of Kncn Does Not Affect Kinocilium and Stereocilia Bundle Morphogenesis and Mechanotransduction in Cochlear Hair Cells.","date":"2018","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/30254566","citation_count":7,"is_preprint":false},{"pmid":"31925639","id":"PMC_31925639","title":"Druggable exosites of the human kino-pocketome.","date":"2020","source":"Journal of computer-aided molecular design","url":"https://pubmed.ncbi.nlm.nih.gov/31925639","citation_count":6,"is_preprint":false},{"pmid":"28597937","id":"PMC_28597937","title":"Frustration-guided motion planning reveals conformational transitions in proteins.","date":"2017","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/28597937","citation_count":6,"is_preprint":false},{"pmid":"40126181","id":"PMC_40126181","title":"Colorectal Tumors in Diverse Patient Populations Feature a Spectrum of Somatic Mutational Profiles.","date":"2025","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/40126181","citation_count":4,"is_preprint":false},{"pmid":"38537770","id":"PMC_38537770","title":"A novel enzyme-linked ligand-sorbent assay (ELLSA) to screening pulmonary tuberculosis: a retrospective cross-sectional study.","date":"2024","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/38537770","citation_count":3,"is_preprint":false},{"pmid":"33194347","id":"PMC_33194347","title":"Cannonball jellyfish digestion: an insight into the lipolytic enzymes of the digestive system.","date":"2020","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/33194347","citation_count":3,"is_preprint":false},{"pmid":"38558992","id":"PMC_38558992","title":"Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.","date":"2024","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38558992","citation_count":1,"is_preprint":false},{"pmid":"40837069","id":"PMC_40837069","title":"Genome-Wide Association Study and Rare Variant Association Studies of Strabismus in the All of Us Research Program.","date":"2025","source":"Ophthalmology science","url":"https://pubmed.ncbi.nlm.nih.gov/40837069","citation_count":1,"is_preprint":false},{"pmid":"41525165","id":"PMC_41525165","title":"Anti-inflammatory and cytoregulatory effects of Corymbia terminalis kino extracts on human keratinocytes.","date":"2026","source":"International journal of environmental health research","url":"https://pubmed.ncbi.nlm.nih.gov/41525165","citation_count":0,"is_preprint":false},{"pmid":"41406052","id":"PMC_41406052","title":"Flavonoids From Corymbia terminalis Kino With Antimicrobial and Anti-Inflammatory Activities.","date":"2025","source":"Chemistry & biodiversity","url":"https://pubmed.ncbi.nlm.nih.gov/41406052","citation_count":0,"is_preprint":false},{"pmid":"37414911","id":"PMC_37414911","title":"Genome-wide DNA methylation analysis in schizophrenia with tardive dyskinesia: a preliminary study.","date":"2023","source":"Genes & genomics","url":"https://pubmed.ncbi.nlm.nih.gov/37414911","citation_count":0,"is_preprint":false},{"pmid":"41675975","id":"PMC_41675975","title":"Rare Variants in Antisense Long Noncoding RNA-Protein-Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder.","date":"2025","source":"Biological psychiatry global open science","url":"https://pubmed.ncbi.nlm.nih.gov/41675975","citation_count":0,"is_preprint":false},{"pmid":"40666340","id":"PMC_40666340","title":"Rare Variants in Antisense lncRNA-Protein Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder.","date":"2025","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40666340","citation_count":0,"is_preprint":false},{"pmid":"9101542","id":"PMC_9101542","title":"[Diagnostic problems associated with colorectal cancer].","date":"1997","source":"Nihon Geka Gakkai zasshi","url":"https://pubmed.ncbi.nlm.nih.gov/9101542","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16722,"output_tokens":605,"usd":0.029621,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6596,"output_tokens":706,"usd":0.025315,"stage2_stop_reason":"end_turn"},"total_usd":0.054936,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through these papers, I need to identify which ones are actually about the human/mammalian KNCN (kinocilin) gene.\n\nPaper [16] is clearly about KNCN (kinocilin) - it directly studies the Kncn gene in mice using CRISPR/Cas9 knockout.\n\nPaper [20] mentions KNCN (kinocilin) as a ligand protein identified in a tuberculosis study context - it identifies KNCN binding to M.tb proteins, but this seems more of an association/screening study.\n\nPapers [27] and [28] mention KNCN in the context of OCD genetics and co-expression analysis - these are genetic association studies with expression correlation, not mechanistic experiments.\n\nPapers [19], [22], [23], [26] mention KNCN in genetic/genomic contexts (mutation associations, methylation) - no mechanistic experiments.\n\nThe remaining papers are clearly about other topics (fungi proteins, cacti, jellyfish, computational tools, etc.) and are not about the KNCN gene.\n\nOnly paper [16] provides a direct experimental mechanistic finding about KNCN protein function.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"Kncn knockout mice generated by CRISPR/Cas9 show no hearing loss, intact inner ear and hair cell structure, and no deficit in mechanotransduction (MET) in cochlear outer hair cells, demonstrating that KNCN is not essential for kinocilium-oriented hair bundle development or mechanotransduction in cochlear hair cells.\",\n      \"method\": \"CRISPR/Cas9 knockout mouse, audiometry, histology, mechanotransduction electrophysiology\",\n      \"journal\": \"Frontiers in molecular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (audiometry + MET recording + histology), multiple orthogonal readouts in single lab; establishes a negative result (dispensability) with rigorous in vivo methods\",\n      \"pmids\": [\"30254566\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KNCN (kinocilin) is a protein enriched in inner ear hair cells and reported to localize to the kinocilium, but genetic knockout in mice demonstrates it is dispensable for kinocilium-oriented hair bundle morphogenesis and mechanotransduction in cochlear hair cells; no other mechanistic function has been experimentally established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KNCN (kinocilin) is a protein enriched in inner ear hair cells whose functional role remains largely uncharacterized. CRISPR/Cas9 knockout mice lack hearing loss and show intact inner ear and hair cell structure with normal mechanotransduction in cochlear outer hair cells, establishing that KNCN is dispensable for kinocilium-oriented hair bundle development and mechanotransduction in cochlear hair cells [#0]. Beyond this negative in vivo result, no molecular activity, binding partner, or alternative function has been experimentally established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether KNCN is required for hair bundle morphogenesis and hearing was unknown; targeted deletion answered this by showing the gene is dispensable for cochlear hair cell development and function.\",\n      \"evidence\": \"CRISPR/Cas9 knockout mouse assessed by audiometry, histology, and mechanotransduction electrophysiology\",\n      \"pmids\": [\"30254566\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not identify any molecular activity or binding partner of KNCN\",\n        \"Possible functional redundancy or vestibular/non-cochlear roles not excluded\",\n        \"Subcellular localization to the kinocilium not directly tested in this knockout study\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function, interaction partners, and the biological reason for KNCN enrichment in hair cells remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical activity assigned\",\n        \"No physical partners identified\",\n        \"No phenotype establishing a required cellular role\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":1,"faith_total":1,"faith_pct":100.0}}