{"gene":"OTOG","run_date":"2026-06-10T05:19:53","timeline":{"discoveries":[{"year":2000,"finding":"Targeted disruption of Otog in mice demonstrated that otogelin is required for anchoring of otoconial membranes and cupulae to the neuroepithelia in the vestibule, and is involved in organizing the fibrillar network of the tectorial membrane (TM) in the cochlea, likely conferring resistance of the TM to sound stimulation.","method":"Targeted gene disruption (knockout mouse), histological and ultrastructural analysis of inner ear acellular membranes","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean loss-of-function knockout with specific structural phenotypic readouts in both vestibular and cochlear compartments, replicated across multiple sensory epithelial patches","pmids":["10655058"],"is_preprint":false},{"year":2000,"finding":"Otogelin is an N-glycosylated protein specifically localized to the acellular membranes of all six sensory epithelial patches of the inner ear: the tectorial membrane (cochlea), the otoconial membranes over the utricular and saccular maculae, and the cupulae over the cristae ampullares (vestibule), placing it as a structural component of these mechanotransduction-associated matrices.","method":"Subtractive cDNA library cloning, protein characterization, and localization in mouse inner ear","journal":"Nature genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Strong — direct localization experiment across multiple tissues in a single study, but biochemical characterization limited to N-glycosylation without full functional reconstitution","pmids":["10655058"],"is_preprint":false}],"current_model":"Otogelin (OTOG) is an N-glycosylated extracellular matrix protein exclusively localized to the acellular membranes of the inner ear (tectorial membrane, otoconial membranes, and cupulae), where it is required for anchoring these membranes to the sensory neuroepithelia and for organizing the fibrillar network of the tectorial membrane, thereby enabling mechanotransduction in both auditory and vestibular sensory epithelia."},"narrative":{"mechanistic_narrative":"Otogelin (OTOG) is an N-glycosylated extracellular matrix protein that serves as a structural component of the acellular membranes of the inner ear, where it is required for the integrity of mechanotransduction-associated matrices in both auditory and vestibular sensory epithelia [PMID:10655058]. It localizes specifically to the acellular membranes overlying all six sensory epithelial patches—the tectorial membrane of the cochlea, the otoconial membranes over the utricular and saccular maculae, and the cupulae over the cristae ampullares [PMID:10655058]. Targeted disruption of Otog in mice established that otogelin anchors the otoconial membranes and cupulae to the underlying vestibular neuroepithelia and organizes the fibrillar network of the tectorial membrane, conferring resistance of the membrane to sound stimulation [PMID:10655058]. Beyond this structural and localization role, no further mechanistic detail—such as direct binding partners or the molecular basis of fibril assembly—has been characterized in the available corpus.","teleology":[{"year":2000,"claim":"It was unknown what molecular component anchors and organizes the inner ear's acellular membranes; cloning and localization identified otogelin as an N-glycosylated matrix protein present across all six sensory epithelial patches, establishing it as a candidate structural element of mechanotransduction-associated matrices.","evidence":"Subtractive cDNA cloning, protein characterization, and immunolocalization in mouse inner ear","pmids":["10655058"],"confidence":"Medium","gaps":["Biochemical characterization limited to N-glycosylation; no full functional reconstitution","No direct binding partners or matrix interaction mechanism identified","Mechanism of fibril network assembly unresolved"]},{"year":2000,"claim":"Whether otogelin is functionally required for inner ear membrane architecture was untested; knockout mice showed defective anchoring of otoconial membranes and cupulae and disorganized tectorial membrane fibrils, establishing otogelin as essential for membrane attachment and TM organization in both vestibular and cochlear compartments.","evidence":"Targeted gene disruption (knockout mouse) with histological and ultrastructural analysis","pmids":["10655058"],"confidence":"High","gaps":["Molecular partners mediating anchoring to neuroepithelia not identified","Mechanism by which it confers TM resistance to sound stimulation not defined at molecular level","Human disease relevance not addressed in this corpus"]},{"year":null,"claim":"The direct molecular interactions through which otogelin organizes the fibrillar network and anchors acellular membranes to sensory epithelia remain undefined.","evidence":"No further mechanistic studies in the available corpus","pmids":[],"confidence":"High","gaps":["No identified protein binding partners","No structural model of the fibrillar network","No reconstitution of matrix assembly"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0031012","term_label":"extracellular matrix","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6ZRI0","full_name":"Otogelin","aliases":[],"length_aa":2925,"mass_kda":314.8,"function":"Glycoprotein specific to acellular membranes of the inner ear. May be required for the anchoring of the otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule. May be involved in the organization and/or stabilization of the fibrillar network that compose the tectorial membrane in the cochlea. May play a role in mechanotransduction processes (By similarity)","subcellular_location":"Apical cell membrane; Secreted, extracellular space","url":"https://www.uniprot.org/uniprotkb/Q6ZRI0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/OTOG","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/OTOG","total_profiled":1310},"omim":[{"mim_id":"621527","title":"TRANSMEMBRANE PROTEIN 145; TMEM145","url":"https://www.omim.org/entry/621527"},{"mim_id":"614945","title":"DEAFNESS, AUTOSOMAL RECESSIVE 18B; DFNB18B","url":"https://www.omim.org/entry/614945"},{"mim_id":"614925","title":"OTOGELIN-LIKE PROTEIN; OTOGL","url":"https://www.omim.org/entry/614925"},{"mim_id":"607038","title":"OTOANCORIN; OTOA","url":"https://www.omim.org/entry/607038"},{"mim_id":"604487","title":"OTOGELIN; OTOG","url":"https://www.omim.org/entry/604487"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"pituitary gland","ntpm":1.2}],"url":"https://www.proteinatlas.org/search/OTOG"},"hgnc":{"alias_symbol":["mlemp","OTGN","FLJ46346"],"prev_symbol":[]},"alphafold":{"accession":"Q6ZRI0","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRI0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRI0-2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6ZRI0-2-F1-predicted_aligned_error_v6.png","plddt_mean":59.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=OTOG","jax_strain_url":"https://www.jax.org/strain/search?query=OTOG"},"sequence":{"accession":"Q6ZRI0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZRI0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZRI0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZRI0"}},"corpus_meta":[{"pmid":"10655058","id":"PMC_10655058","title":"Targeted disruption of otog results in deafness and severe imbalance.","date":"2000","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10655058","citation_count":124,"is_preprint":false},{"pmid":"33136635","id":"PMC_33136635","title":"Burden of Rare Variants in the OTOG Gene in Familial Meniere's Disease.","date":"2020","source":"Ear and hearing","url":"https://pubmed.ncbi.nlm.nih.gov/33136635","citation_count":52,"is_preprint":false},{"pmid":"29800624","id":"PMC_29800624","title":"A novel early truncation mutation in OTOG causes prelingual mild hearing loss without vestibular dysfunction.","date":"2018","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29800624","citation_count":13,"is_preprint":false},{"pmid":"31645975","id":"PMC_31645975","title":"Clinical characteristics with long-term follow-up of four Okinawan families with moderate hearing loss caused by an OTOG variant.","date":"2019","source":"Human genome variation","url":"https://pubmed.ncbi.nlm.nih.gov/31645975","citation_count":10,"is_preprint":false},{"pmid":"34118384","id":"PMC_34118384","title":"Prediction and interpretation of rare missense variant in OTOG associated with hearing loss.","date":"2021","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/34118384","citation_count":6,"is_preprint":false},{"pmid":"38519595","id":"PMC_38519595","title":"An overload of missense variants in the OTOG gene may drive a higher prevalence of familial Meniere disease in the European population.","date":"2024","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38519595","citation_count":6,"is_preprint":false},{"pmid":"32244554","id":"PMC_32244554","title":"Compound Phenotype Due to Recessive Variants in LARP7 and OTOG Genes Disclosed by an Integrated Approach of SNP-Array and Whole Exome Sequencing.","date":"2020","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/32244554","citation_count":6,"is_preprint":false},{"pmid":"39858607","id":"PMC_39858607","title":"Novel OTOG Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort.","date":"2025","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/39858607","citation_count":2,"is_preprint":false},{"pmid":"40565546","id":"PMC_40565546","title":"Replication of Missense OTOG Gene Variants in a Brazilian Patient with Menière's Disease.","date":"2025","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/40565546","citation_count":1,"is_preprint":false},{"pmid":"40307680","id":"PMC_40307680","title":"Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for screening colorectal cancer in the Otog Front Banner.","date":"2025","source":"BMC gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/40307680","citation_count":0,"is_preprint":false},{"pmid":"40389292","id":"PMC_40389292","title":"Novel variant in OTOG gene in consanguineous family with sensorineural hearing loss.","date":"2025","source":"BMJ case reports","url":"https://pubmed.ncbi.nlm.nih.gov/40389292","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.26.25326273","title":"Replication of missense OTOG gene variants in a Brazilian cohort of Menière’s Disease","date":"2025-04-28","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.26.25326273","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.08.13.25333146","title":"The <i>TECTB-C225Y</i> Variant Causing Autosomal Dominant Deafness in a Nicaraguan Family Enhances Sensitivity to Noise-Induced Hearing Loss in Mice","date":"2025-08-14","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.13.25333146","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8215,"output_tokens":603,"usd":0.016845,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6926,"output_tokens":1324,"usd":0.033865,"stage2_stop_reason":"end_turn"},"total_usd":0.05071,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"Targeted disruption of Otog in mice demonstrated that otogelin is required for anchoring of otoconial membranes and cupulae to the neuroepithelia in the vestibule, and is involved in organizing the fibrillar network of the tectorial membrane (TM) in the cochlea, likely conferring resistance of the TM to sound stimulation.\",\n      \"method\": \"Targeted gene disruption (knockout mouse), histological and ultrastructural analysis of inner ear acellular membranes\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean loss-of-function knockout with specific structural phenotypic readouts in both vestibular and cochlear compartments, replicated across multiple sensory epithelial patches\",\n      \"pmids\": [\"10655058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Otogelin is an N-glycosylated protein specifically localized to the acellular membranes of all six sensory epithelial patches of the inner ear: the tectorial membrane (cochlea), the otoconial membranes over the utricular and saccular maculae, and the cupulae over the cristae ampullares (vestibule), placing it as a structural component of these mechanotransduction-associated matrices.\",\n      \"method\": \"Subtractive cDNA library cloning, protein characterization, and localization in mouse inner ear\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Strong — direct localization experiment across multiple tissues in a single study, but biochemical characterization limited to N-glycosylation without full functional reconstitution\",\n      \"pmids\": [\"10655058\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Otogelin (OTOG) is an N-glycosylated extracellular matrix protein exclusively localized to the acellular membranes of the inner ear (tectorial membrane, otoconial membranes, and cupulae), where it is required for anchoring these membranes to the sensory neuroepithelia and for organizing the fibrillar network of the tectorial membrane, thereby enabling mechanotransduction in both auditory and vestibular sensory epithelia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Otogelin (OTOG) is an N-glycosylated extracellular matrix protein that serves as a structural component of the acellular membranes of the inner ear, where it is required for the integrity of mechanotransduction-associated matrices in both auditory and vestibular sensory epithelia [#0, #1]. It localizes specifically to the acellular membranes overlying all six sensory epithelial patches—the tectorial membrane of the cochlea, the otoconial membranes over the utricular and saccular maculae, and the cupulae over the cristae ampullares [#1]. Targeted disruption of Otog in mice established that otogelin anchors the otoconial membranes and cupulae to the underlying vestibular neuroepithelia and organizes the fibrillar network of the tectorial membrane, conferring resistance of the membrane to sound stimulation [#0]. Beyond this structural and localization role, no further mechanistic detail—such as direct binding partners or the molecular basis of fibril assembly—has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"It was unknown what molecular component anchors and organizes the inner ear's acellular membranes; cloning and localization identified otogelin as an N-glycosylated matrix protein present across all six sensory epithelial patches, establishing it as a candidate structural element of mechanotransduction-associated matrices.\",\n      \"evidence\": \"Subtractive cDNA cloning, protein characterization, and immunolocalization in mouse inner ear\",\n      \"pmids\": [\"10655058\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Biochemical characterization limited to N-glycosylation; no full functional reconstitution\",\n        \"No direct binding partners or matrix interaction mechanism identified\",\n        \"Mechanism of fibril network assembly unresolved\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Whether otogelin is functionally required for inner ear membrane architecture was untested; knockout mice showed defective anchoring of otoconial membranes and cupulae and disorganized tectorial membrane fibrils, establishing otogelin as essential for membrane attachment and TM organization in both vestibular and cochlear compartments.\",\n      \"evidence\": \"Targeted gene disruption (knockout mouse) with histological and ultrastructural analysis\",\n      \"pmids\": [\"10655058\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular partners mediating anchoring to neuroepithelia not identified\",\n        \"Mechanism by which it confers TM resistance to sound stimulation not defined at molecular level\",\n        \"Human disease relevance not addressed in this corpus\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular interactions through which otogelin organizes the fibrillar network and anchors acellular membranes to sensory epithelia remain undefined.\",\n      \"evidence\": \"No further mechanistic studies in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No identified protein binding partners\",\n        \"No structural model of the fibrillar network\",\n        \"No reconstitution of matrix assembly\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031012\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}