{"gene":"WDR87","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":2022,"finding":"WDR87 localizes to the middle piece of spermatozoa flagella, migrating through the manchette during spermiogenesis, and physically interacts with CFAP47 (a cilia- and flagella-associated protein) to form a complex involved in sperm tail assembly. CFAP47 is required for WDR87 transportation during flagella biogenesis, as loss-of-function CFAP47 mutations dramatically reduce both CFAP47 and WDR87 protein levels in spermatozoa.","method":"Immunofluorescence localization, co-immunoprecipitation/pulldown interaction assay, immunoblotting in CFAP47-mutant human spermatozoa","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 2–3 — reciprocal interaction identified with Co-IP, subcellular localization by immunofluorescence with functional consequence, single lab study","pmids":["36571501"],"is_preprint":false},{"year":2016,"finding":"WDR87 was identified as a protein that interacts with the human PRE-PIK3C2B cis-regulatory element, detected by DNA affinity purification followed by mass spectrometry in HEK, U87, and HeLa cell lines, placing WDR87 in association with COMPASS-like (MLL/MLL4-containing) activating complexes.","method":"DNA affinity purification followed by mass spectrometry (three biological replicates in multiple cell lines)","journal":"Biochimica et biophysica acta. Gene regulatory mechanisms","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single method (mass spectrometry-based pulldown); no functional validation of WDR87's specific role","pmids":["27932267"],"is_preprint":false},{"year":2016,"finding":"Biallelic inactivating mutation in WDR87 was identified in a single family with non-syndromic pediatric cataract, and iSyTE developmental lens expression analysis corroborated WDR87's proposed role in the lens.","method":"Whole-exome sequencing, positional mapping, iSyTE lens expression analysis","journal":"Human genetics","confidence":"Low","confidence_rationale":"Tier 3–4 — genetic association with expression-based corroboration, no direct functional/mechanistic experiment performed on the protein","pmids":["27878435"],"is_preprint":false}],"current_model":"WDR87 is a WD40-repeat domain protein that localizes to the manchette and middle piece of the spermatozoa flagellum, where it interacts with CFAP47 to participate in sperm tail assembly; it has also been genetically linked to non-syndromic pediatric cataract through biallelic loss-of-function mutations, and found to associate with chromatin regulatory complexes at a human Polycomb/Trithorax responsive element."},"narrative":{"teleology":[{"year":2016,"claim":"Whether WDR87 associates with chromatin regulatory complexes was addressed by identifying it as a protein bound to a human Polycomb/Trithorax responsive element (PRE-PIK3C2B), placing it in the context of COMPASS-like complexes.","evidence":"DNA affinity purification followed by mass spectrometry in HEK, U87, and HeLa cell lines","pmids":["27932267"],"confidence":"Low","gaps":["Single method (mass spectrometry pulldown) without reciprocal or functional validation of WDR87's specific role at the regulatory element","No evidence that WDR87 directly binds DNA versus being an indirect complex component","No knockdown or knockout experiment to assess functional contribution"]},{"year":2016,"claim":"Whether WDR87 contributes to lens development was addressed by identifying biallelic loss-of-function mutations in a single family with non-syndromic pediatric cataract, establishing a candidate disease gene link.","evidence":"Whole-exome sequencing, positional mapping, and iSyTE developmental lens expression analysis in a single family","pmids":["27878435"],"confidence":"Low","gaps":["Single family with no replication cohort or animal model rescue experiment","No mechanistic data on how WDR87 loss leads to cataract","Expression-based corroboration does not establish causality"]},{"year":2022,"claim":"The subcellular role of WDR87 in spermiogenesis was established by showing it localizes to the manchette and flagellar middle piece, physically interacts with CFAP47, and depends on CFAP47 for its transport and stability during sperm tail assembly.","evidence":"Immunofluorescence, co-immunoprecipitation/pulldown, and immunoblotting in human spermatozoa including CFAP47-mutant samples","pmids":["36571501"],"confidence":"Medium","gaps":["No WDR87 knockout or knockdown model to assess its independent contribution to flagellar assembly","Structural basis of the WDR87–CFAP47 interaction is unknown","Whether WDR87 has enzymatic or scaffolding activity in the complex is unresolved"]},{"year":null,"claim":"It remains unknown whether WDR87's roles in flagellar assembly and lens development reflect a shared molecular mechanism or tissue-specific functions, and no direct loss-of-function model for WDR87 has been reported.","evidence":"","pmids":[],"confidence":"Low","gaps":["No animal or cellular knockout/knockdown model for WDR87","No enzymatic activity or structural model determined","Relationship between chromatin-associated and cytoskeletal functions is unexplored"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":[],"partners":["CFAP47"],"other_free_text":[]},"mechanistic_narrative":"WDR87 is a WD40-repeat domain protein that localizes to the manchette and middle piece of the spermatozoa flagellum during spermiogenesis, where it physically interacts with CFAP47 to participate in sperm tail assembly; loss-of-function CFAP47 mutations dramatically reduce WDR87 protein levels, indicating that CFAP47 is required for WDR87 transport during flagella biogenesis [PMID:36571501]. Biallelic inactivating mutations in WDR87 have been identified in a family with non-syndromic pediatric cataract, supported by developmental lens expression data [PMID:27878435]."},"prefetch_data":{"uniprot":{"accession":"Q6ZQQ6","full_name":"WD repeat-containing protein 87","aliases":["Testis development protein NYD-SP11"],"length_aa":2873,"mass_kda":333.2,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6ZQQ6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/WDR87","classification":"Not Classified","n_dependent_lines":7,"n_total_lines":1208,"dependency_fraction":0.005794701986754967},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/WDR87","total_profiled":1310},"omim":[{"mim_id":"620274","title":"WD REPEAT-CONTAINING PROTEIN 87; WDR87","url":"https://www.omim.org/entry/620274"},{"mim_id":"301059","title":"SPERMATOGENIC FAILURE, X-LINKED, 3; SPGFX3","url":"https://www.omim.org/entry/301059"},{"mim_id":"301057","title":"CILIA- AND FLAGELLA-ASSOCIATED PROTEIN 47; CFAP47","url":"https://www.omim.org/entry/301057"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"testis","ntpm":15.9}],"url":"https://www.proteinatlas.org/search/WDR87"},"hgnc":{"alias_symbol":["NYD-SP11"],"prev_symbol":[]},"alphafold":{"accession":"Q6ZQQ6","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZQQ6","model_url":"","pae_url":"","plddt_mean":null},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=WDR87","jax_strain_url":"https://www.jax.org/strain/search?query=WDR87"},"sequence":{"accession":"Q6ZQQ6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6ZQQ6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6ZQQ6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6ZQQ6"}},"corpus_meta":[{"pmid":"27878435","id":"PMC_27878435","title":"Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.","date":"2016","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27878435","citation_count":72,"is_preprint":false},{"pmid":"26622071","id":"PMC_26622071","title":"Phenotypes of Recessive Pediatric Cataract in a Cohort of Children with Identified Homozygous Gene Mutations (An American Ophthalmological Society Thesis).","date":"2015","source":"Transactions of the American Ophthalmological Society","url":"https://pubmed.ncbi.nlm.nih.gov/26622071","citation_count":38,"is_preprint":false},{"pmid":"34620846","id":"PMC_34620846","title":"Genomic alterations associated with mutational signatures, DNA damage repair and chromatin remodeling pathways in cervical carcinoma.","date":"2021","source":"NPJ genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34620846","citation_count":16,"is_preprint":false},{"pmid":"36571501","id":"PMC_36571501","title":"WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly.","date":"2022","source":"Molecular human reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/36571501","citation_count":12,"is_preprint":false},{"pmid":"27932267","id":"PMC_27932267","title":"Human PRE-PIK3C2B, an intronic cis-element with dual function of activation and repression.","date":"2016","source":"Biochimica et biophysica acta. Gene regulatory mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/27932267","citation_count":3,"is_preprint":false},{"pmid":"42010917","id":"PMC_42010917","title":"Integrative Multi-omics Approaches Identify Biomarkers Associated with Progression from Arthralgia to Rheumatoid Arthritis.","date":"2026","source":"Arthritis & rheumatology (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/42010917","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4859,"output_tokens":817,"usd":0.013416},"stage2":{"model":"claude-opus-4-6","input_tokens":4002,"output_tokens":1075,"usd":0.070328},"total_usd":0.083744,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"WDR87 localizes to the middle piece of spermatozoa flagella, migrating through the manchette during spermiogenesis, and physically interacts with CFAP47 (a cilia- and flagella-associated protein) to form a complex involved in sperm tail assembly. CFAP47 is required for WDR87 transportation during flagella biogenesis, as loss-of-function CFAP47 mutations dramatically reduce both CFAP47 and WDR87 protein levels in spermatozoa.\",\n      \"method\": \"Immunofluorescence localization, co-immunoprecipitation/pulldown interaction assay, immunoblotting in CFAP47-mutant human spermatozoa\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — reciprocal interaction identified with Co-IP, subcellular localization by immunofluorescence with functional consequence, single lab study\",\n      \"pmids\": [\"36571501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"WDR87 was identified as a protein that interacts with the human PRE-PIK3C2B cis-regulatory element, detected by DNA affinity purification followed by mass spectrometry in HEK, U87, and HeLa cell lines, placing WDR87 in association with COMPASS-like (MLL/MLL4-containing) activating complexes.\",\n      \"method\": \"DNA affinity purification followed by mass spectrometry (three biological replicates in multiple cell lines)\",\n      \"journal\": \"Biochimica et biophysica acta. Gene regulatory mechanisms\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single method (mass spectrometry-based pulldown); no functional validation of WDR87's specific role\",\n      \"pmids\": [\"27932267\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Biallelic inactivating mutation in WDR87 was identified in a single family with non-syndromic pediatric cataract, and iSyTE developmental lens expression analysis corroborated WDR87's proposed role in the lens.\",\n      \"method\": \"Whole-exome sequencing, positional mapping, iSyTE lens expression analysis\",\n      \"journal\": \"Human genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3–4 — genetic association with expression-based corroboration, no direct functional/mechanistic experiment performed on the protein\",\n      \"pmids\": [\"27878435\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR87 is a WD40-repeat domain protein that localizes to the manchette and middle piece of the spermatozoa flagellum, where it interacts with CFAP47 to participate in sperm tail assembly; it has also been genetically linked to non-syndromic pediatric cataract through biallelic loss-of-function mutations, and found to associate with chromatin regulatory complexes at a human Polycomb/Trithorax responsive element.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"WDR87 is a WD40-repeat domain protein that localizes to the manchette and middle piece of the spermatozoa flagellum during spermiogenesis, where it physically interacts with CFAP47 to participate in sperm tail assembly; loss-of-function CFAP47 mutations dramatically reduce WDR87 protein levels, indicating that CFAP47 is required for WDR87 transport during flagella biogenesis [PMID:36571501]. Biallelic inactivating mutations in WDR87 have been identified in a family with non-syndromic pediatric cataract, supported by developmental lens expression data [PMID:27878435].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether WDR87 associates with chromatin regulatory complexes was addressed by identifying it as a protein bound to a human Polycomb/Trithorax responsive element (PRE-PIK3C2B), placing it in the context of COMPASS-like complexes.\",\n      \"evidence\": \"DNA affinity purification followed by mass spectrometry in HEK, U87, and HeLa cell lines\",\n      \"pmids\": [\"27932267\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (mass spectrometry pulldown) without reciprocal or functional validation of WDR87's specific role at the regulatory element\",\n        \"No evidence that WDR87 directly binds DNA versus being an indirect complex component\",\n        \"No knockdown or knockout experiment to assess functional contribution\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether WDR87 contributes to lens development was addressed by identifying biallelic loss-of-function mutations in a single family with non-syndromic pediatric cataract, establishing a candidate disease gene link.\",\n      \"evidence\": \"Whole-exome sequencing, positional mapping, and iSyTE developmental lens expression analysis in a single family\",\n      \"pmids\": [\"27878435\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single family with no replication cohort or animal model rescue experiment\",\n        \"No mechanistic data on how WDR87 loss leads to cataract\",\n        \"Expression-based corroboration does not establish causality\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The subcellular role of WDR87 in spermiogenesis was established by showing it localizes to the manchette and flagellar middle piece, physically interacts with CFAP47, and depends on CFAP47 for its transport and stability during sperm tail assembly.\",\n      \"evidence\": \"Immunofluorescence, co-immunoprecipitation/pulldown, and immunoblotting in human spermatozoa including CFAP47-mutant samples\",\n      \"pmids\": [\"36571501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No WDR87 knockout or knockdown model to assess its independent contribution to flagellar assembly\",\n        \"Structural basis of the WDR87–CFAP47 interaction is unknown\",\n        \"Whether WDR87 has enzymatic or scaffolding activity in the complex is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether WDR87's roles in flagellar assembly and lens development reflect a shared molecular mechanism or tissue-specific functions, and no direct loss-of-function model for WDR87 has been reported.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No animal or cellular knockout/knockdown model for WDR87\",\n        \"No enzymatic activity or structural model determined\",\n        \"Relationship between chromatin-associated and cytoskeletal functions is unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CFAP47\"],\n    \"other_free_text\": []\n  }\n}\n```"}