{"gene":"ODAD1","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2012,"finding":"CCDC114 (ODAD1) localizes along the entire length of human cilia and is required for microtubular attachment of outer dynein arms (ODAs) to the axoneme; loss-of-function mutations cause complete absence of ciliary ODAs resulting in immotile cilia.","method":"Immunofluorescence localization of CCDC114 in human cilia; electron microscopy of patient cilia showing ODA absence; identification of homologous relationship to Chlamydomonas ODA docking complex component DCC2","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiment combined with ultrastructural EM analysis of patient cells, replicated across two independent labs in the same year (PMIDs 23261303 and 23261302)","pmids":["23261303","23261302"],"is_preprint":false},{"year":2018,"finding":"CCDC114 (ODAD1) localizes at the basal body of cilia, and knockdown of CCDC114 reduces cilia occurrence in hRPE1 cells, indicating a role in primary (non-motile) cilia biogenesis in addition to motile cilia.","method":"Immunofluorescence localization in renal tissue and hRPE1 cells; siRNA knockdown with quantification of cilia number","journal":"Journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single method (KD + cilia counting), no rescue experiment","pmids":["30291279"],"is_preprint":false},{"year":2022,"finding":"A splice mutation (c.1502+5G>A) in ODAD1 produces a truncated protein that retains partial function: it attaches to the axoneme, allows assembly of some ODAs, and supports significant residual ciliary activity, explaining an unusually mild PCD phenotype.","method":"Molecular analysis of splice mutation, immunofluorescence and electron microscopy of nasal epithelial cell cultures, ciliary beat frequency analysis","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional studies in patient-derived cells using multiple orthogonal methods (molecular, immunofluorescence, EM, beat frequency), single lab","pmids":["35163670"],"is_preprint":false},{"year":2023,"finding":"Splice-site mutations in ODAD1 (c.71-2A>C; c.598-2A>C) produce truncated proteins that lack wild-type ODAD1, cause outer dynein arm defects and decreased ciliary beat frequency; additionally, truncated ODAD1 proteins inhibit the interaction between wild-type ODAD1 and ODAD3.","method":"Whole-exome sequencing, RT-PCR/molecular analysis of aberrant splicing, transmission electron microscopy of axonemes, ciliary beat frequency measurement, co-immunoprecipitation of ODAD1-ODAD3 interaction","journal":"Frontiers in genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods in one study (molecular, EM, beat frequency, Co-IP), single lab","pmids":["38028630"],"is_preprint":false},{"year":2026,"finding":"Loss-of-function ODAD1 variants cause complete loss of outer dynein arms and docking complexes in ciliary axonemes; ODAD1 deficiency additionally reduces multiciliated cell (MCC) abundance, causes misoriented basal bodies, impairs multiciliogenesis, and induces actin cytoskeletal remodeling including aberrant F-actin bundling. Pharmacological inhibition of actin polymerization (cytochalasin B) partially rescues MCC abundance and multiciliogenesis. Lentiviral re-expression of wild-type ODAD1 in patient-derived organoids restores ODA assembly and rescues coordinated ciliary beating.","method":"Patient-derived nasal epithelial cells and ALI cultures, transmission electron microscopy, cryo-electron microscopy, proteomic profiling, immunostaining, pharmacological rescue with cytochalasin B, lentiviral ODAD1 re-expression in patient organoids","journal":"Cell discovery","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods including cryo-EM structural analysis, proteomic profiling, pharmacological rescue, and genetic rescue (lentiviral re-expression) in a single rigorous study","pmids":["41916967"],"is_preprint":false}],"current_model":"ODAD1 (CCDC114) is a structural component of the outer dynein arm docking complex (ODA-DC) that localizes along the full length of motile cilia and at the basal body, where it is essential for anchoring outer dynein arms to the axonemal microtubules; loss of ODAD1 abolishes ODA assembly, impairs ciliary beat frequency, reduces multiciliated cell abundance, causes misoriented basal bodies, and induces aberrant F-actin cytoskeletal remodeling in the epithelium, with the actin dysregulation being pharmacologically reversible and the ODA/beating defects rescuable by wild-type ODAD1 re-expression; truncated ODAD1 proteins from splice mutations can retain partial axonemal attachment and ODA assembly function and can act as dominant inhibitors of the ODAD1–ODAD3 interaction."},"narrative":{"mechanistic_narrative":"ODAD1 (CCDC114) is a structural component of the outer dynein arm docking complex (ODA-DC) that anchors outer dynein arms (ODAs) to the axonemal microtubules of motile cilia, and its loss causes primary ciliary dyskinesia through immotile cilia [PMID:23261303, PMID:23261302]. It localizes along the entire length of cilia and at the basal body, and loss-of-function mutations abolish ODA assembly, producing complete absence of ciliary ODAs and immotile cilia [PMID:23261303, PMID:23261302]. ODAD1 docks ODAs in part through a physical interaction with ODAD3; truncated ODAD1 proteins produced by splice mutations act as dominant inhibitors of the ODAD1–ODAD3 interaction [PMID:38028630]. Beyond its core docking role, ODAD1 deficiency reduces multiciliated cell abundance, misorients basal bodies, impairs multiciliogenesis, and drives aberrant F-actin cytoskeletal remodeling that is partially reversed by pharmacological inhibition of actin polymerization, with ODA assembly and coordinated beating restored by wild-type ODAD1 re-expression in patient organoids [PMID:41916967]. Truncating splice mutations can yield proteins that retain partial axonemal attachment and residual ODA assembly, accounting for milder disease [PMID:35163670]; ODAD1 also localizes to the basal body of primary cilia and contributes to primary ciliogenesis [PMID:30291279].","teleology":[{"year":2012,"claim":"Established that ODAD1 is the docking-complex component required to attach outer dynein arms to the axoneme, defining the molecular lesion behind a class of immotile-cilia disease.","evidence":"Immunofluorescence localization in human cilia plus electron microscopy of patient cilia showing ODA absence, with homology to Chlamydomonas docking complex component DCC2","pmids":["23261303","23261302"],"confidence":"High","gaps":["Atomic-level architecture of the docking complex not resolved","Direct binding partners within the ODA-DC not yet mapped"]},{"year":2018,"claim":"Extended ODAD1 function beyond motile cilia by placing it at the basal body and implicating it in primary (non-motile) ciliogenesis.","evidence":"Immunofluorescence in renal tissue and hRPE1 cells with siRNA knockdown and cilia counting","pmids":["30291279"],"confidence":"Medium","gaps":["No rescue experiment to confirm specificity","Single method (knockdown + counting) without mechanistic detail of how ODAD1 affects primary cilia formation"]},{"year":2022,"claim":"Showed that not all ODAD1 truncations are null — a splice variant can retain partial axonemal attachment and residual ODA assembly, explaining genotype-phenotype variability.","evidence":"Molecular analysis of c.1502+5G>A splice mutation with immunofluorescence, EM, and beat-frequency analysis of patient nasal epithelial cultures","pmids":["35163670"],"confidence":"Medium","gaps":["Structural basis of residual attachment not defined","Single lab, single allele"]},{"year":2023,"claim":"Identified a physical ODAD1–ODAD3 interaction and demonstrated that truncated ODAD1 can act as a dominant inhibitor of this interaction, providing a mechanism for dominant-negative disease alleles.","evidence":"Whole-exome sequencing, RT-PCR splicing analysis, TEM, beat-frequency measurement, and co-immunoprecipitation of ODAD1-ODAD3","pmids":["38028630"],"confidence":"Medium","gaps":["Co-IP without reciprocal or structural validation of the interaction interface","Single lab"]},{"year":2026,"claim":"Broadened ODAD1 function from a pure docking factor to a regulator of multiciliated-cell development and actin cytoskeletal homeostasis, and demonstrated genetic rescue establishing causality.","evidence":"Patient-derived nasal ALI cultures and organoids with TEM, cryo-EM, proteomics, immunostaining, cytochalasin B rescue, and lentiviral ODAD1 re-expression","pmids":["41916967"],"confidence":"High","gaps":["Molecular link between ODAD1 loss and F-actin dysregulation not defined","How ODAD1 influences basal body orientation and MCC differentiation is unresolved"]},{"year":null,"claim":"The mechanistic connection between ODAD1's axonemal docking role and its effects on basal body orientation, multiciliogenesis, and actin remodeling remains unexplained.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined signaling pathway linking ODAD1 to actin cytoskeleton","Complete stoichiometry and structure of the ODA-DC and its full subunit complement not resolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,4]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[4]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0,4]}],"complexes":["outer dynein arm docking complex (ODA-DC)"],"partners":["ODAD3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96M63","full_name":"Outer dynein arm-docking complex subunit 1","aliases":["Coiled-coil domain-containing protein 114"],"length_aa":670,"mass_kda":75.0,"function":"Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton, cilium axoneme","url":"https://www.uniprot.org/uniprotkb/Q96M63/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ODAD1","classification":"Not Classified","n_dependent_lines":20,"n_total_lines":1208,"dependency_fraction":0.016556291390728478},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ODAD1","total_profiled":1310},"omim":[{"mim_id":"619669","title":"PIERCER OF MICROTUBULE WALL 2; PIERCE2","url":"https://www.omim.org/entry/619669"},{"mim_id":"615067","title":"CILIARY DYSKINESIA, PRIMARY, 20; CILD20","url":"https://www.omim.org/entry/615067"},{"mim_id":"615038","title":"OUTER DYNEIN ARM DOCKING COMPLEX SUBUNIT 1; ODAD1","url":"https://www.omim.org/entry/615038"},{"mim_id":"614502","title":"PIERCER OF MICROTUBULE WALL 1; PIERCE1","url":"https://www.omim.org/entry/614502"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mid piece","reliability":"Supported"},{"location":"Connecting piece","reliability":"Additional"},{"location":"Principal piece","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"choroid plexus","ntpm":27.5},{"tissue":"fallopian tube","ntpm":24.0},{"tissue":"testis","ntpm":21.1}],"url":"https://www.proteinatlas.org/search/ODAD1"},"hgnc":{"alias_symbol":["FLJ32926","CILD20"],"prev_symbol":["CCDC114"]},"alphafold":{"accession":"Q96M63","domains":[{"cath_id":"1.20.5","chopping":"14-100","consensus_level":"medium","plddt":91.2933,"start":14,"end":100},{"cath_id":"1.20.5","chopping":"107-231","consensus_level":"medium","plddt":95.3711,"start":107,"end":231}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M63","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M63-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96M63-F1-predicted_aligned_error_v6.png","plddt_mean":71.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ODAD1","jax_strain_url":"https://www.jax.org/strain/search?query=ODAD1"},"sequence":{"accession":"Q96M63","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96M63.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96M63/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96M63"}},"corpus_meta":[{"pmid":"23261303","id":"PMC_23261303","title":"Splice-site mutations in the axonemal outer dynein arm docking complex gene CCDC114 cause primary ciliary dyskinesia.","date":"2012","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23261303","citation_count":148,"is_preprint":false},{"pmid":"23261302","id":"PMC_23261302","title":"Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia.","date":"2012","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23261302","citation_count":112,"is_preprint":false},{"pmid":"30291279","id":"PMC_30291279","title":"CCDC114 is mutated in patient with a complex phenotype combining primary ciliary dyskinesia, sensorineural deafness, and renal disease.","date":"2018","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30291279","citation_count":21,"is_preprint":false},{"pmid":"35343062","id":"PMC_35343062","title":"Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation.","date":"2022","source":"American journal of medical genetics. Part C, Seminars in medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35343062","citation_count":11,"is_preprint":false},{"pmid":"32855706","id":"PMC_32855706","title":"Identification of a CCDC114 variant in a Han-Chinese patient with situs inversus.","date":"2020","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32855706","citation_count":9,"is_preprint":false},{"pmid":"35163670","id":"PMC_35163670","title":"Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35163670","citation_count":8,"is_preprint":false},{"pmid":"34116668","id":"PMC_34116668","title":"CCDC114, DNAI2 and TOP2A involves in the effects of tibolone treatment on postmenopausal endometrium.","date":"2021","source":"BMC women's health","url":"https://pubmed.ncbi.nlm.nih.gov/34116668","citation_count":1,"is_preprint":false},{"pmid":"38028630","id":"PMC_38028630","title":"ODAD1 variants resulting from splice-site mutations retain partial function and cause primary ciliary dyskinesia with outer dynein arm defects.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38028630","citation_count":1,"is_preprint":false},{"pmid":"40783954","id":"PMC_40783954","title":"[Clinical and genetic analysis of a case of Kartagener syndrome with obstructive azoospermia induced by biallelic variation of CCDC114].","date":"2025","source":"Zhonghua nan ke xue = National journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/40783954","citation_count":0,"is_preprint":false},{"pmid":"41916967","id":"PMC_41916967","title":"Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia.","date":"2026","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/41916967","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6972,"output_tokens":1497,"usd":0.021685,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8257,"output_tokens":2151,"usd":0.04753,"stage2_stop_reason":"end_turn"},"total_usd":0.069215,"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\": 2012,\n      \"finding\": \"CCDC114 (ODAD1) localizes along the entire length of human cilia and is required for microtubular attachment of outer dynein arms (ODAs) to the axoneme; loss-of-function mutations cause complete absence of ciliary ODAs resulting in immotile cilia.\",\n      \"method\": \"Immunofluorescence localization of CCDC114 in human cilia; electron microscopy of patient cilia showing ODA absence; identification of homologous relationship to Chlamydomonas ODA docking complex component DCC2\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiment combined with ultrastructural EM analysis of patient cells, replicated across two independent labs in the same year (PMIDs 23261303 and 23261302)\",\n      \"pmids\": [\"23261303\", \"23261302\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CCDC114 (ODAD1) localizes at the basal body of cilia, and knockdown of CCDC114 reduces cilia occurrence in hRPE1 cells, indicating a role in primary (non-motile) cilia biogenesis in addition to motile cilia.\",\n      \"method\": \"Immunofluorescence localization in renal tissue and hRPE1 cells; siRNA knockdown with quantification of cilia number\",\n      \"journal\": \"Journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (KD + cilia counting), no rescue experiment\",\n      \"pmids\": [\"30291279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"A splice mutation (c.1502+5G>A) in ODAD1 produces a truncated protein that retains partial function: it attaches to the axoneme, allows assembly of some ODAs, and supports significant residual ciliary activity, explaining an unusually mild PCD phenotype.\",\n      \"method\": \"Molecular analysis of splice mutation, immunofluorescence and electron microscopy of nasal epithelial cell cultures, ciliary beat frequency analysis\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional studies in patient-derived cells using multiple orthogonal methods (molecular, immunofluorescence, EM, beat frequency), single lab\",\n      \"pmids\": [\"35163670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Splice-site mutations in ODAD1 (c.71-2A>C; c.598-2A>C) produce truncated proteins that lack wild-type ODAD1, cause outer dynein arm defects and decreased ciliary beat frequency; additionally, truncated ODAD1 proteins inhibit the interaction between wild-type ODAD1 and ODAD3.\",\n      \"method\": \"Whole-exome sequencing, RT-PCR/molecular analysis of aberrant splicing, transmission electron microscopy of axonemes, ciliary beat frequency measurement, co-immunoprecipitation of ODAD1-ODAD3 interaction\",\n      \"journal\": \"Frontiers in genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods in one study (molecular, EM, beat frequency, Co-IP), single lab\",\n      \"pmids\": [\"38028630\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Loss-of-function ODAD1 variants cause complete loss of outer dynein arms and docking complexes in ciliary axonemes; ODAD1 deficiency additionally reduces multiciliated cell (MCC) abundance, causes misoriented basal bodies, impairs multiciliogenesis, and induces actin cytoskeletal remodeling including aberrant F-actin bundling. Pharmacological inhibition of actin polymerization (cytochalasin B) partially rescues MCC abundance and multiciliogenesis. Lentiviral re-expression of wild-type ODAD1 in patient-derived organoids restores ODA assembly and rescues coordinated ciliary beating.\",\n      \"method\": \"Patient-derived nasal epithelial cells and ALI cultures, transmission electron microscopy, cryo-electron microscopy, proteomic profiling, immunostaining, pharmacological rescue with cytochalasin B, lentiviral ODAD1 re-expression in patient organoids\",\n      \"journal\": \"Cell discovery\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods including cryo-EM structural analysis, proteomic profiling, pharmacological rescue, and genetic rescue (lentiviral re-expression) in a single rigorous study\",\n      \"pmids\": [\"41916967\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ODAD1 (CCDC114) is a structural component of the outer dynein arm docking complex (ODA-DC) that localizes along the full length of motile cilia and at the basal body, where it is essential for anchoring outer dynein arms to the axonemal microtubules; loss of ODAD1 abolishes ODA assembly, impairs ciliary beat frequency, reduces multiciliated cell abundance, causes misoriented basal bodies, and induces aberrant F-actin cytoskeletal remodeling in the epithelium, with the actin dysregulation being pharmacologically reversible and the ODA/beating defects rescuable by wild-type ODAD1 re-expression; truncated ODAD1 proteins from splice mutations can retain partial axonemal attachment and ODA assembly function and can act as dominant inhibitors of the ODAD1–ODAD3 interaction.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ODAD1 (CCDC114) is a structural component of the outer dynein arm docking complex (ODA-DC) that anchors outer dynein arms (ODAs) to the axonemal microtubules of motile cilia, and its loss causes primary ciliary dyskinesia through immotile cilia [#0]. It localizes along the entire length of cilia and at the basal body, and loss-of-function mutations abolish ODA assembly, producing complete absence of ciliary ODAs and immotile cilia [#0]. ODAD1 docks ODAs in part through a physical interaction with ODAD3; truncated ODAD1 proteins produced by splice mutations act as dominant inhibitors of the ODAD1–ODAD3 interaction [#3]. Beyond its core docking role, ODAD1 deficiency reduces multiciliated cell abundance, misorients basal bodies, impairs multiciliogenesis, and drives aberrant F-actin cytoskeletal remodeling that is partially reversed by pharmacological inhibition of actin polymerization, with ODA assembly and coordinated beating restored by wild-type ODAD1 re-expression in patient organoids [#4]. Truncating splice mutations can yield proteins that retain partial axonemal attachment and residual ODA assembly, accounting for milder disease [#2]; ODAD1 also localizes to the basal body of primary cilia and contributes to primary ciliogenesis [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that ODAD1 is the docking-complex component required to attach outer dynein arms to the axoneme, defining the molecular lesion behind a class of immotile-cilia disease.\",\n      \"evidence\": \"Immunofluorescence localization in human cilia plus electron microscopy of patient cilia showing ODA absence, with homology to Chlamydomonas docking complex component DCC2\",\n      \"pmids\": [\"23261303\", \"23261302\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-level architecture of the docking complex not resolved\", \"Direct binding partners within the ODA-DC not yet mapped\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extended ODAD1 function beyond motile cilia by placing it at the basal body and implicating it in primary (non-motile) ciliogenesis.\",\n      \"evidence\": \"Immunofluorescence in renal tissue and hRPE1 cells with siRNA knockdown and cilia counting\",\n      \"pmids\": [\"30291279\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No rescue experiment to confirm specificity\", \"Single method (knockdown + counting) without mechanistic detail of how ODAD1 affects primary cilia formation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed that not all ODAD1 truncations are null — a splice variant can retain partial axonemal attachment and residual ODA assembly, explaining genotype-phenotype variability.\",\n      \"evidence\": \"Molecular analysis of c.1502+5G>A splice mutation with immunofluorescence, EM, and beat-frequency analysis of patient nasal epithelial cultures\",\n      \"pmids\": [\"35163670\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of residual attachment not defined\", \"Single lab, single allele\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified a physical ODAD1–ODAD3 interaction and demonstrated that truncated ODAD1 can act as a dominant inhibitor of this interaction, providing a mechanism for dominant-negative disease alleles.\",\n      \"evidence\": \"Whole-exome sequencing, RT-PCR splicing analysis, TEM, beat-frequency measurement, and co-immunoprecipitation of ODAD1-ODAD3\",\n      \"pmids\": [\"38028630\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-IP without reciprocal or structural validation of the interaction interface\", \"Single lab\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Broadened ODAD1 function from a pure docking factor to a regulator of multiciliated-cell development and actin cytoskeletal homeostasis, and demonstrated genetic rescue establishing causality.\",\n      \"evidence\": \"Patient-derived nasal ALI cultures and organoids with TEM, cryo-EM, proteomics, immunostaining, cytochalasin B rescue, and lentiviral ODAD1 re-expression\",\n      \"pmids\": [\"41916967\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular link between ODAD1 loss and F-actin dysregulation not defined\", \"How ODAD1 influences basal body orientation and MCC differentiation is unresolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanistic connection between ODAD1's axonemal docking role and its effects on basal body orientation, multiciliogenesis, and actin remodeling remains unexplained.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No defined signaling pathway linking ODAD1 to actin cytoskeleton\", \"Complete stoichiometry and structure of the ODA-DC and its full subunit complement not resolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"complexes\": [\"outer dynein arm docking complex (ODA-DC)\"],\n    \"partners\": [\"ODAD3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}