{"gene":"WDR89","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2017,"finding":"Wdr89 knockdown in mice produces a thinner corpus callosum phenotype, placing it among WDR genes required for brain connectivity and neuronal morphology.","method":"In vivo mouse inactivation screen; corpus callosum morphology assessment across 26 WDR genes","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Wdr89 is one of many genes screened; only a phenotypic readout (thinner corpus callosum) is reported for Wdr89 specifically, with no molecular mechanism described for WDR89 itself","pmids":["29078390"],"is_preprint":false},{"year":2025,"finding":"WDR89 (human orthologue of yeast Bcl1) is found in the proximity of human RPL10A (the orthologue of yeast Rpl1) by TurboID-based proximity labelling, suggesting an evolutionarily conserved function as a dedicated chaperone for the large ribosomal subunit protein Rpl1/RPL10A.","method":"TurboID-based proximity labelling (proxiOME) in human cells; yeast ortholog Bcl1 verified by direct pull-down and in vitro reconstitution of trimeric complex","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labelling in human cells is indirect, but the yeast ortholog Bcl1 is validated by direct interaction assay and in vitro reconstitution; the human WDR89 finding itself rests on a single proximity labelling observation without direct functional follow-up","pmids":["bio_10.1101_2025.09.18.677003"],"is_preprint":true},{"year":2026,"finding":"WDR89 protein is stabilized (thermally shifted) upon treatment with the replacement PFAS compound HFPO-DA (GenX) in a thermal proteome profiling experiment, indicating direct or near-direct physical engagement between GenX and WDR89; molecular docking independently verified target engagement, suggesting a potential role in chromatin/complex assembly.","method":"Thermal proteome profiling (TPP) and cellular thermal shift assay (CETSA); molecular docking","journal":"Environmental science & technology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — thermal stabilization and docking are indirect evidence of binding; no functional consequence of WDR89–PFAS interaction experimentally established; single study","pmids":["41883243"],"is_preprint":false}],"current_model":"WDR89 is the human orthologue of yeast Bcl1 and localizes to the proximity of the large ribosomal subunit protein RPL10A, consistent with a conserved role as a dedicated chaperone that facilitates safe nuclear transfer and loading of the Rpl1/RPL10A ribosomal protein onto pre-60S subunits; in vivo, its loss in mice produces a thinner corpus callosum, but the underlying molecular mechanism for this phenotype remains undefined."},"narrative":{"mechanistic_narrative":"WDR89 is the human orthologue of yeast Bcl1 and localizes in the proximity of the large ribosomal subunit protein RPL10A (the orthologue of yeast Rpl1), consistent with a conserved role as a dedicated chaperone facilitating handling and loading of the Rpl1/RPL10A ribosomal protein, a function validated for the yeast orthologue by direct pull-down and in vitro reconstitution of a trimeric complex [PMID:bio_10.1101_2025.09.18.677003]. In vivo, knockdown of Wdr89 in mice produces a thinner corpus callosum, placing it among WDR genes required for brain connectivity and neuronal morphology [PMID:29078390], though the molecular basis of this phenotype is not characterized in the available corpus. Beyond the proximity relationship to RPL10A and the murine phenotype, no direct biochemical mechanism for human WDR89 has been established in the available corpus.","teleology":[{"year":2017,"claim":"Established the first in vivo phenotype for WDR89 by asking whether it is among WDR genes needed for brain wiring, showing its loss disrupts a major axonal commissure.","evidence":"In vivo mouse inactivation screen across 26 WDR genes with corpus callosum morphology assessment","pmids":["29078390"],"confidence":"Low","gaps":["Phenotypic readout only; no molecular mechanism described for WDR89","Does not establish whether the corpus callosum defect is cell-autonomous or downstream of a ribosomal/biogenesis role","No cellular localization or interaction data for WDR89 in this study"]},{"year":2025,"claim":"Addressed the molecular function of WDR89 by mapping its protein neighborhood, positioning it near RPL10A and implying a conserved chaperone role for the large ribosomal subunit protein.","evidence":"TurboID-based proximity labelling (proxiOME) in human cells; yeast ortholog Bcl1 verified by direct pull-down and in vitro reconstitution of a trimeric complex (preprint)","pmids":["bio_10.1101_2025.09.18.677003"],"confidence":"Medium","gaps":["Human WDR89 finding rests on a single proximity-labelling observation without direct functional follow-up","Direct binding and reconstitution were shown for the yeast orthologue, not human WDR89 itself","No demonstration that WDR89 loss impairs RPL10A loading or 60S subunit biogenesis in human cells"]},{"year":2026,"claim":"Tested whether WDR89 physically engages an environmental PFAS compound, finding thermal stabilization upon GenX treatment consistent with direct binding.","evidence":"Thermal proteome profiling and CETSA with molecular docking validation","pmids":["41883243"],"confidence":"Low","gaps":["Thermal stabilization and docking are indirect evidence of binding awaiting orthogonal biophysical confirmation","No functional consequence of the WDR89-PFAS interaction established","Single study; relevance to the ribosomal/chaperone role unknown"]},{"year":null,"claim":"Whether WDR89 functionally acts as a chaperone loading RPL10A onto pre-60S particles in human cells, and how this connects to the corpus callosum phenotype, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct binding or reconstitution demonstrated for human WDR89","No link established between ribosomal function and the neuronal phenotype","No structural model of human WDR89 in the available corpus"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["RPL10A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96FK6","full_name":"WD repeat-containing protein 89","aliases":[],"length_aa":387,"mass_kda":43.2,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q96FK6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR89","classification":"Not Classified","n_dependent_lines":71,"n_total_lines":1208,"dependency_fraction":0.058774834437086095},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/WDR89","total_profiled":1310},"omim":[{"mim_id":"621458","title":"WD REPEAT-CONTAINING PROTEIN 89; WDR89","url":"https://www.omim.org/entry/621458"},{"mim_id":"607992","title":"SURP AND G-PATCH DOMAINS-CONTAINING PROTEIN 1; SUGP1","url":"https://www.omim.org/entry/607992"},{"mim_id":"604979","title":"CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR 6; CPSF6","url":"https://www.omim.org/entry/604979"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Intermediate filaments","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/WDR89"},"hgnc":{"alias_symbol":["MGC9907"],"prev_symbol":["C14orf150"]},"alphafold":{"accession":"Q96FK6","domains":[{"cath_id":"2.130.10.10","chopping":"24-214","consensus_level":"medium","plddt":93.9115,"start":24,"end":214}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FK6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FK6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96FK6-F1-predicted_aligned_error_v6.png","plddt_mean":87.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR89","jax_strain_url":"https://www.jax.org/strain/search?query=WDR89"},"sequence":{"accession":"Q96FK6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96FK6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96FK6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96FK6"}},"corpus_meta":[{"pmid":"29078390","id":"PMC_29078390","title":"WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/29078390","citation_count":80,"is_preprint":false},{"pmid":"34966342","id":"PMC_34966342","title":"A Novel Immune Classification for Predicting Immunotherapy Responsiveness in Patients With Adamantinomatous Craniopharyngioma.","date":"2021","source":"Frontiers in neurology","url":"https://pubmed.ncbi.nlm.nih.gov/34966342","citation_count":15,"is_preprint":false},{"pmid":"35678525","id":"PMC_35678525","title":"The genomic landscape of Cronkhite-Canada syndrome: Possible clues for pathogenesis.","date":"2022","source":"Journal of digestive diseases","url":"https://pubmed.ncbi.nlm.nih.gov/35678525","citation_count":12,"is_preprint":false},{"pmid":"38517939","id":"PMC_38517939","title":"Canadian COVID-19 host genetics cohort replicates known severity associations.","date":"2024","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/38517939","citation_count":4,"is_preprint":false},{"pmid":"32842198","id":"PMC_32842198","title":"[Study on expression and mechanism of serum differential proteins after rush immunotherapy of allergic rhinitis].","date":"2020","source":"Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery","url":"https://pubmed.ncbi.nlm.nih.gov/32842198","citation_count":3,"is_preprint":false},{"pmid":"39906820","id":"PMC_39906820","title":"Discovery of mutated oncodriver genes associated with glioblastoma originated from stem cells of subventricular zone through whole exome sequence profile analysis, and drug repurposing.","date":"2025","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/39906820","citation_count":3,"is_preprint":false},{"pmid":"39662264","id":"PMC_39662264","title":"CircSugp1 interacts with CPSF6 to modulate intestinal mucosa repair by regulating alternative polyadenylation-mediated shortening of the Wdr89 3'UTR.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39662264","citation_count":1,"is_preprint":false},{"pmid":"42072359","id":"PMC_42072359","title":"Integrative Whole-Genome and Epigenome Profiling of cfDNA in Familial Prostate Cancer: Insights from a Pilot Study.","date":"2026","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/42072359","citation_count":0,"is_preprint":false},{"pmid":"41883243","id":"PMC_41883243","title":"Applying Thermal Proteome Profiling to Per- and Polyfluoroalkyl Substances (PFAS): Proteome-Wide Identification of Molecular Targets and Early Events.","date":"2026","source":"Environmental science & technology","url":"https://pubmed.ncbi.nlm.nih.gov/41883243","citation_count":0,"is_preprint":false},{"pmid":"39473539","id":"PMC_39473539","title":"Genome-Wide Association Study for Test-Day Milk Yield, Proteins, and Composition Traits of Crossbred Dairy Cattle in Ethiopia.","date":"2024","source":"International journal of genomics","url":"https://pubmed.ncbi.nlm.nih.gov/39473539","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.09.18.677003","title":"Exploration of the proxiOME of large subunit ribosomal proteins reveals Acl1 and Bcl1 as cooperating dedicated chaperones of Rpl1","date":"2025-09-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.18.677003","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9018,"output_tokens":861,"usd":0.019984,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7317,"output_tokens":1435,"usd":0.03623,"stage2_stop_reason":"end_turn"},"total_usd":0.056214,"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\": 2017,\n      \"finding\": \"Wdr89 knockdown in mice produces a thinner corpus callosum phenotype, placing it among WDR genes required for brain connectivity and neuronal morphology.\",\n      \"method\": \"In vivo mouse inactivation screen; corpus callosum morphology assessment across 26 WDR genes\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Wdr89 is one of many genes screened; only a phenotypic readout (thinner corpus callosum) is reported for Wdr89 specifically, with no molecular mechanism described for WDR89 itself\",\n      \"pmids\": [\"29078390\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"WDR89 (human orthologue of yeast Bcl1) is found in the proximity of human RPL10A (the orthologue of yeast Rpl1) by TurboID-based proximity labelling, suggesting an evolutionarily conserved function as a dedicated chaperone for the large ribosomal subunit protein Rpl1/RPL10A.\",\n      \"method\": \"TurboID-based proximity labelling (proxiOME) in human cells; yeast ortholog Bcl1 verified by direct pull-down and in vitro reconstitution of trimeric complex\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labelling in human cells is indirect, but the yeast ortholog Bcl1 is validated by direct interaction assay and in vitro reconstitution; the human WDR89 finding itself rests on a single proximity labelling observation without direct functional follow-up\",\n      \"pmids\": [\"bio_10.1101_2025.09.18.677003\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"WDR89 protein is stabilized (thermally shifted) upon treatment with the replacement PFAS compound HFPO-DA (GenX) in a thermal proteome profiling experiment, indicating direct or near-direct physical engagement between GenX and WDR89; molecular docking independently verified target engagement, suggesting a potential role in chromatin/complex assembly.\",\n      \"method\": \"Thermal proteome profiling (TPP) and cellular thermal shift assay (CETSA); molecular docking\",\n      \"journal\": \"Environmental science & technology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — thermal stabilization and docking are indirect evidence of binding; no functional consequence of WDR89–PFAS interaction experimentally established; single study\",\n      \"pmids\": [\"41883243\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR89 is the human orthologue of yeast Bcl1 and localizes to the proximity of the large ribosomal subunit protein RPL10A, consistent with a conserved role as a dedicated chaperone that facilitates safe nuclear transfer and loading of the Rpl1/RPL10A ribosomal protein onto pre-60S subunits; in vivo, its loss in mice produces a thinner corpus callosum, but the underlying molecular mechanism for this phenotype remains undefined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR89 is the human orthologue of yeast Bcl1 and localizes in the proximity of the large ribosomal subunit protein RPL10A (the orthologue of yeast Rpl1), consistent with a conserved role as a dedicated chaperone facilitating handling and loading of the Rpl1/RPL10A ribosomal protein, a function validated for the yeast orthologue by direct pull-down and in vitro reconstitution of a trimeric complex [#1]. In vivo, knockdown of Wdr89 in mice produces a thinner corpus callosum, placing it among WDR genes required for brain connectivity and neuronal morphology [#0], though the molecular basis of this phenotype is not characterized in the available corpus. Beyond the proximity relationship to RPL10A and the murine phenotype, no direct biochemical mechanism for human WDR89 has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established the first in vivo phenotype for WDR89 by asking whether it is among WDR genes needed for brain wiring, showing its loss disrupts a major axonal commissure.\",\n      \"evidence\": \"In vivo mouse inactivation screen across 26 WDR genes with corpus callosum morphology assessment\",\n      \"pmids\": [\"29078390\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Phenotypic readout only; no molecular mechanism described for WDR89\",\n        \"Does not establish whether the corpus callosum defect is cell-autonomous or downstream of a ribosomal/biogenesis role\",\n        \"No cellular localization or interaction data for WDR89 in this study\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Addressed the molecular function of WDR89 by mapping its protein neighborhood, positioning it near RPL10A and implying a conserved chaperone role for the large ribosomal subunit protein.\",\n      \"evidence\": \"TurboID-based proximity labelling (proxiOME) in human cells; yeast ortholog Bcl1 verified by direct pull-down and in vitro reconstitution of a trimeric complex (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.09.18.677003\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Human WDR89 finding rests on a single proximity-labelling observation without direct functional follow-up\",\n        \"Direct binding and reconstitution were shown for the yeast orthologue, not human WDR89 itself\",\n        \"No demonstration that WDR89 loss impairs RPL10A loading or 60S subunit biogenesis in human cells\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Tested whether WDR89 physically engages an environmental PFAS compound, finding thermal stabilization upon GenX treatment consistent with direct binding.\",\n      \"evidence\": \"Thermal proteome profiling and CETSA with molecular docking validation\",\n      \"pmids\": [\"41883243\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Thermal stabilization and docking are indirect evidence of binding awaiting orthogonal biophysical confirmation\",\n        \"No functional consequence of the WDR89-PFAS interaction established\",\n        \"Single study; relevance to the ribosomal/chaperone role unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether WDR89 functionally acts as a chaperone loading RPL10A onto pre-60S particles in human cells, and how this connects to the corpus callosum phenotype, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct binding or reconstitution demonstrated for human WDR89\",\n        \"No link established between ribosomal function and the neuronal phenotype\",\n        \"No structural model of human WDR89 in the available corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"RPL10A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":null}