{"gene":"WDR93","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2012,"finding":"C1d-87 (WDR93/FAP297) was identified as a novel subunit of the C1d projection of the ciliary central apparatus in Chlamydomonas reinhardtii, and the C1d projection (containing WDR93 along with FAP54, FAP46, FAP74, and FAP221/Pcdp1) is required for normal flagellar motility, phototaxis, photoshock response, and control of interdoublet sliding velocity.","method":"Isolation and characterization of a Chlamydomonas fap46-1 null mutant lacking the C1d projection; identification of C1d-87 as a novel subunit via biochemical/structural analysis of the mutant","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean null mutant with defined motility phenotype and identification of WDR93 as a C1d subunit, single lab but multiple phenotypic readouts","pmids":["22573824"],"is_preprint":false},{"year":2024,"finding":"FAP297 (WDR93) was identified as an A-kinase anchoring protein (AKAP) in the central-pair microtubules of Chlamydomonas reinhardtii cilia, detected via co-immunoprecipitation using FAP174 (an RIIα-like protein) as bait, placing WDR93 in a PKA-anchoring signaling complex within the ciliary central pair.","method":"Co-immunoprecipitation with anti-FAP174 antibody from enriched central-pair microtubule fractions followed by mass spectrometry; RII D/D domain used as bait to identify FAP297 as an AKAP","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal Co-IP/MS from enriched fractions, single lab, single method identifying FAP297 as an AKAP interactor","pmids":["38140814"],"is_preprint":false},{"year":2023,"finding":"WDR93 is a central ciliary apparatus C1d projection component conserved across vertebrates; gene-disrupting changes in WDR93 in specific bird lineages (landfowl, geese and others) result in loss of WDR93 transcripts, and these species concurrently lost another C1d component, CFAP46, through large segmental deletions, linking WDR93 to mucociliary defence.","method":"Comparative genomic analysis of ~500 vertebrate genomes; transcript expression analysis confirming absence of WDR93 mRNA in species with gene-disrupting changes","journal":"Royal Society open science","confidence":"Low","confidence_rationale":"Tier 3 / Moderate — comparative genomics and transcript analysis in non-mammalian species, no direct functional reconstitution or mutagenesis of the protein","pmids":["37621660"],"is_preprint":false}],"current_model":"WDR93 (FAP297/C1d-87/CFAP297) is a structural subunit of the C1d projection of the ciliary central apparatus and functions as an A-kinase anchoring protein (AKAP) within the central-pair microtubules, where it participates in a PKA-anchoring signaling complex; loss of the C1d projection disrupts flagellar motility, phototaxis, photoshock response, and interdoublet sliding velocity control."},"narrative":{"mechanistic_narrative":"WDR93 (FAP297/C1d-87/CFAP297) is a structural subunit of the C1d projection of the ciliary central apparatus, where it supports the motility functions of cilia and flagella [PMID:22573824]. In Chlamydomonas, WDR93 assembles into the C1d projection alongside FAP54, FAP46, FAP74, and FAP221/Pcdp1, and loss of this projection disrupts flagellar motility, phototaxis, the photoshock response, and the control of interdoublet sliding velocity [PMID:22573824]. Within the central-pair microtubules WDR93 also acts as an A-kinase anchoring protein (AKAP), associating with the RIIα-like protein FAP174 to form part of a PKA-anchoring signaling complex that couples the central apparatus to kinase signaling [PMID:38140814]. Beyond its role as a conserved C1d projection component these mechanistic features have not been further characterized in the available corpus.","teleology":[{"year":2012,"claim":"Established WDR93 as a bona fide structural subunit of the ciliary central apparatus and tied the C1d projection it belongs to directly to flagellar motility control.","evidence":"Characterization of a Chlamydomonas fap46-1 null mutant lacking the C1d projection, with biochemical/structural identification of C1d-87 as a novel subunit and multiple motility readouts","pmids":["22573824"],"confidence":"Medium","gaps":["Does not define WDR93's molecular activity or how it physically docks within C1d","Phenotypes derive from loss of the whole projection, not from WDR93-specific perturbation","No mammalian or vertebrate functional validation"]},{"year":2023,"claim":"Tested whether WDR93 is a conserved central-apparatus component across vertebrates by tracking its gene-disrupting loss alongside another C1d component.","evidence":"Comparative genomics across ~500 vertebrate genomes plus transcript analysis showing absence of WDR93 mRNA in bird lineages that concurrently lost CFAP46","pmids":["37621660"],"confidence":"Low","gaps":["Correlative genomic/transcript evidence with no direct functional reconstitution or mutagenesis","Mucociliary defence link is inferred, not experimentally demonstrated","Does not address WDR93 function in mammals"]},{"year":2024,"claim":"Addressed how the central apparatus integrates kinase signaling by identifying WDR93 as an AKAP within a PKA-anchoring complex.","evidence":"Co-immunoprecipitation and mass spectrometry from enriched Chlamydomonas central-pair microtubule fractions using the RIIα-like FAP174 (RII D/D domain) as bait","pmids":["38140814"],"confidence":"Medium","gaps":["Single method/single lab identification of the AKAP interaction","PKA-anchoring function not validated by functional or structural reconstitution","Downstream phosphorylation substrates of the anchored kinase unidentified"]},{"year":null,"claim":"How WDR93 mediates AKAP function and how its C1d structural role and PKA-anchoring role are mechanistically integrated to control ciliary beat remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of WDR93 within the C1d projection","No mammalian/human functional or disease characterization","Mechanism linking PKA anchoring to interdoublet sliding velocity control undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1]}],"pathway":[],"complexes":["C1d projection of the ciliary central apparatus","central-pair PKA-anchoring (AKAP) complex"],"partners":["FAP46","FAP54","FAP74","FAP221","FAP174","CFAP46"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6P2C0","full_name":"WD repeat-containing protein 93","aliases":[],"length_aa":686,"mass_kda":77.4,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6P2C0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR93","classification":"Not Classified","n_dependent_lines":15,"n_total_lines":1208,"dependency_fraction":0.012417218543046357},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/WDR93","total_profiled":1310},"omim":[{"mim_id":"619891","title":"WD REPEAT-CONTAINING PROTEIN 93; WDR93","url":"https://www.omim.org/entry/619891"},{"mim_id":"610753","title":"ALOPECIA AREATA 2; AA2","url":"https://www.omim.org/entry/610753"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Actin filaments","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"choroid plexus","ntpm":6.6},{"tissue":"fallopian tube","ntpm":8.4},{"tissue":"testis","ntpm":10.8}],"url":"https://www.proteinatlas.org/search/WDR93"},"hgnc":{"alias_symbol":["FAP297","C1d-87","CFAP297"],"prev_symbol":[]},"alphafold":{"accession":"Q6P2C0","domains":[{"cath_id":"2.130.10.10","chopping":"99-235_270-285","consensus_level":"high","plddt":89.0188,"start":99,"end":285},{"cath_id":"1.20.5","chopping":"653-685","consensus_level":"high","plddt":68.7221,"start":653,"end":685}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2C0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2C0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2C0-F1-predicted_aligned_error_v6.png","plddt_mean":77.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR93","jax_strain_url":"https://www.jax.org/strain/search?query=WDR93"},"sequence":{"accession":"Q6P2C0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6P2C0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6P2C0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2C0"}},"corpus_meta":[{"pmid":"25558065","id":"PMC_25558065","title":"Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.","date":"2014","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/25558065","citation_count":381,"is_preprint":false},{"pmid":"22573824","id":"PMC_22573824","title":"A FAP46 mutant provides new insights into the function and assembly of the C1d complex of the ciliary central apparatus.","date":"2012","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/22573824","citation_count":38,"is_preprint":false},{"pmid":"37621660","id":"PMC_37621660","title":"Concurrent loss of ciliary genes WDR93 and CFAP46 in phylogenetically distant birds.","date":"2023","source":"Royal Society open science","url":"https://pubmed.ncbi.nlm.nih.gov/37621660","citation_count":7,"is_preprint":false},{"pmid":"38140814","id":"PMC_38140814","title":"A-kinase anchoring proteins are enriched in the central pair microtubules of motile cilia in Chlamydomonas reinhardtii.","date":"2024","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/38140814","citation_count":6,"is_preprint":false},{"pmid":"40272718","id":"PMC_40272718","title":"Establishing the causative link between CFAP221 variants and asthenoteratozoospermia in humans.","date":"2025","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/40272718","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4524,"output_tokens":954,"usd":0.013941,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7376,"output_tokens":1586,"usd":0.038265,"stage2_stop_reason":"end_turn"},"total_usd":0.052206,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"C1d-87 (WDR93/FAP297) was identified as a novel subunit of the C1d projection of the ciliary central apparatus in Chlamydomonas reinhardtii, and the C1d projection (containing WDR93 along with FAP54, FAP46, FAP74, and FAP221/Pcdp1) is required for normal flagellar motility, phototaxis, photoshock response, and control of interdoublet sliding velocity.\",\n      \"method\": \"Isolation and characterization of a Chlamydomonas fap46-1 null mutant lacking the C1d projection; identification of C1d-87 as a novel subunit via biochemical/structural analysis of the mutant\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean null mutant with defined motility phenotype and identification of WDR93 as a C1d subunit, single lab but multiple phenotypic readouts\",\n      \"pmids\": [\"22573824\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FAP297 (WDR93) was identified as an A-kinase anchoring protein (AKAP) in the central-pair microtubules of Chlamydomonas reinhardtii cilia, detected via co-immunoprecipitation using FAP174 (an RIIα-like protein) as bait, placing WDR93 in a PKA-anchoring signaling complex within the ciliary central pair.\",\n      \"method\": \"Co-immunoprecipitation with anti-FAP174 antibody from enriched central-pair microtubule fractions followed by mass spectrometry; RII D/D domain used as bait to identify FAP297 as an AKAP\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal Co-IP/MS from enriched fractions, single lab, single method identifying FAP297 as an AKAP interactor\",\n      \"pmids\": [\"38140814\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"WDR93 is a central ciliary apparatus C1d projection component conserved across vertebrates; gene-disrupting changes in WDR93 in specific bird lineages (landfowl, geese and others) result in loss of WDR93 transcripts, and these species concurrently lost another C1d component, CFAP46, through large segmental deletions, linking WDR93 to mucociliary defence.\",\n      \"method\": \"Comparative genomic analysis of ~500 vertebrate genomes; transcript expression analysis confirming absence of WDR93 mRNA in species with gene-disrupting changes\",\n      \"journal\": \"Royal Society open science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — comparative genomics and transcript analysis in non-mammalian species, no direct functional reconstitution or mutagenesis of the protein\",\n      \"pmids\": [\"37621660\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR93 (FAP297/C1d-87/CFAP297) is a structural subunit of the C1d projection of the ciliary central apparatus and functions as an A-kinase anchoring protein (AKAP) within the central-pair microtubules, where it participates in a PKA-anchoring signaling complex; loss of the C1d projection disrupts flagellar motility, phototaxis, photoshock response, and interdoublet sliding velocity control.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR93 (FAP297/C1d-87/CFAP297) is a structural subunit of the C1d projection of the ciliary central apparatus, where it supports the motility functions of cilia and flagella [#0]. In Chlamydomonas, WDR93 assembles into the C1d projection alongside FAP54, FAP46, FAP74, and FAP221/Pcdp1, and loss of this projection disrupts flagellar motility, phototaxis, the photoshock response, and the control of interdoublet sliding velocity [#0]. Within the central-pair microtubules WDR93 also acts as an A-kinase anchoring protein (AKAP), associating with the RIIα-like protein FAP174 to form part of a PKA-anchoring signaling complex that couples the central apparatus to kinase signaling [#1]. Beyond its role as a conserved C1d projection component these mechanistic features have not been further characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established WDR93 as a bona fide structural subunit of the ciliary central apparatus and tied the C1d projection it belongs to directly to flagellar motility control.\",\n      \"evidence\": \"Characterization of a Chlamydomonas fap46-1 null mutant lacking the C1d projection, with biochemical/structural identification of C1d-87 as a novel subunit and multiple motility readouts\",\n      \"pmids\": [\"22573824\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not define WDR93's molecular activity or how it physically docks within C1d\", \"Phenotypes derive from loss of the whole projection, not from WDR93-specific perturbation\", \"No mammalian or vertebrate functional validation\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Tested whether WDR93 is a conserved central-apparatus component across vertebrates by tracking its gene-disrupting loss alongside another C1d component.\",\n      \"evidence\": \"Comparative genomics across ~500 vertebrate genomes plus transcript analysis showing absence of WDR93 mRNA in bird lineages that concurrently lost CFAP46\",\n      \"pmids\": [\"37621660\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Correlative genomic/transcript evidence with no direct functional reconstitution or mutagenesis\", \"Mucociliary defence link is inferred, not experimentally demonstrated\", \"Does not address WDR93 function in mammals\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Addressed how the central apparatus integrates kinase signaling by identifying WDR93 as an AKAP within a PKA-anchoring complex.\",\n      \"evidence\": \"Co-immunoprecipitation and mass spectrometry from enriched Chlamydomonas central-pair microtubule fractions using the RIIα-like FAP174 (RII D/D domain) as bait\",\n      \"pmids\": [\"38140814\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method/single lab identification of the AKAP interaction\", \"PKA-anchoring function not validated by functional or structural reconstitution\", \"Downstream phosphorylation substrates of the anchored kinase unidentified\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How WDR93 mediates AKAP function and how its C1d structural role and PKA-anchoring role are mechanistically integrated to control ciliary beat remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of WDR93 within the C1d projection\", \"No mammalian/human functional or disease characterization\", \"Mechanism linking PKA anchoring to interdoublet sliding velocity control undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"C1d projection of the ciliary central apparatus\", \"central-pair PKA-anchoring (AKAP) complex\"],\n    \"partners\": [\"FAP46\", \"FAP54\", \"FAP74\", \"FAP221\", \"FAP174\", \"CFAP46\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}