{"gene":"WDR87","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":2022,"finding":"WDR87 localizes to the middle piece of the spermatozoa tail and physically interacts with CFAP47 (a cilia- and flagella-associated protein) in the flagellar midpiece, forming a complex involved in spermatozoa tail assembly. During spermiogenesis, WDR87 migrates from perinuclear cytoplasm through the manchette to the sperm tail middle piece. Loss-of-function of CFAP47 (due to patient mutations) dramatically reduces CFAP47 protein and also significantly decreases WDR87 expression and mislocalization, indicating CFAP47 is required for WDR87 transport during flagella biogenesis.","method":"Immunofluorescence staining (subcellular localization during spermatogenesis), co-immunoprecipitation / protein interaction assay (WDR87–CFAP47 interaction), immunoblotting in patient spermatozoa with CFAP47 mutations","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — reciprocal interaction shown, localization with functional consequence established, patient validation with two orthogonal methods (IF + immunoblot), single lab","pmids":["36571501"],"is_preprint":false},{"year":2016,"finding":"WDR87 was identified as a protein that interacts with the human PRE-PIK3C2B cis-regulatory DNA element, detected by DNA affinity purification followed by mass spectrometry in three cell lines (HEK, U87, HeLa), suggesting a role in chromatin regulatory complex assembly at Polycomb/Trithorax responsive elements.","method":"DNA affinity purification followed by mass spectrometry (three biological replicates in three cell lines)","journal":"Biochimica et biophysica acta. Gene regulatory mechanisms","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, DNA pulldown/MS without functional validation specific to WDR87; WDR87 is a minor finding in a paper focused on MLL/EZH2 biology","pmids":["27932267"],"is_preprint":false},{"year":2016,"finding":"Biallelic inactivating mutation in WDR87 was identified in a family with non-syndromic pediatric cataract, implicating WDR87 loss-of-function in lens development; iSyTE developmental lens expression analysis corroborated its expression in the lens.","method":"Whole-exome sequencing with homozygous truncating mutation identification; iSyTE lens expression database corroboration","journal":"Human genetics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — genetic association in a single family with computational expression support, no direct functional/mechanistic experiment performed on WDR87","pmids":["27878435"],"is_preprint":false}],"current_model":"WDR87 is a WD40-repeat domain protein that localizes to the middle piece of the sperm tail flagellum and physically interacts with CFAP47 to form a complex required for spermatozoa tail assembly; CFAP47 is additionally required for proper WDR87 transport during flagella biogenesis, and biallelic loss-of-function mutations in WDR87 are associated with non-syndromic pediatric cataract in humans."},"narrative":{"mechanistic_narrative":"WDR87 is a WD40-repeat protein implicated in flagellar (sperm tail) assembly during spermiogenesis [PMID:36571501]. It localizes to the middle piece of the spermatozoa tail and physically interacts with the cilia- and flagella-associated protein CFAP47 to form a complex required for sperm tail assembly; during spermiogenesis WDR87 migrates from perinuclear cytoplasm through the manchette to the tail middle piece, and CFAP47 is required for its proper transport, since patient CFAP47 loss-of-function reduces and mislocalizes WDR87 [PMID:36571501]. Beyond this flagellar role, no further mechanistic detail on WDR87's biochemical activity has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"An initial association linked WDR87 loss-of-function to a human developmental phenotype, raising the question of where WDR87 acts in vivo.","evidence":"Whole-exome sequencing identifying a biallelic truncating mutation in a single non-syndromic pediatric cataract family, with iSyTE lens expression corroboration","pmids":["27878435"],"confidence":"Low","gaps":["Single family with no functional or rescue experiment on WDR87","No mechanism connecting WDR87 to lens biology established","Genetic association only, causality not demonstrated"]},{"year":2016,"claim":"A proteomic screen placed WDR87 at a chromatin cis-regulatory element, hinting at a possible nuclear/regulatory association, though without WDR87-specific validation.","evidence":"DNA affinity purification followed by mass spectrometry at the PRE-PIK3C2B element across three cell lines","pmids":["27932267"],"confidence":"Low","gaps":["No functional validation specific to WDR87","WDR87 was a minor finding in a paper centered on MLL/EZH2 biology","DNA binding not demonstrated to be direct"]},{"year":2022,"claim":"Establishing WDR87's molecular partner and subcellular itinerary defined its function in sperm tail assembly, answering what cellular process WDR87 contributes to.","evidence":"Immunofluorescence localization across spermatogenesis, co-immunoprecipitation of WDR87 with CFAP47, and immunoblotting in CFAP47-mutant patient spermatozoa","pmids":["36571501"],"confidence":"Medium","gaps":["Single lab; interaction not yet reconstituted with purified components","Catalytic or structural role of WDR87 within the complex undefined","Connection between the flagellar role and the earlier cataract/chromatin observations unexplained"]},{"year":null,"claim":"The biochemical activity of WDR87 and how it reconciles its sperm flagellar role with the reported lens phenotype remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No defined enzymatic or scaffolding activity","No structural model of the WDR87-CFAP47 complex","No mechanism linking WDR87 to lens development"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[0]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["CFAP47"],"other_free_text":[]}},"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":75,"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":40,"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 Multiomics 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":5654,"output_tokens":919,"usd":0.015374,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7373,"output_tokens":1303,"usd":0.03472,"stage2_stop_reason":"end_turn"},"total_usd":0.050094,"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\": 2022,\n      \"finding\": \"WDR87 localizes to the middle piece of the spermatozoa tail and physically interacts with CFAP47 (a cilia- and flagella-associated protein) in the flagellar midpiece, forming a complex involved in spermatozoa tail assembly. During spermiogenesis, WDR87 migrates from perinuclear cytoplasm through the manchette to the sperm tail middle piece. Loss-of-function of CFAP47 (due to patient mutations) dramatically reduces CFAP47 protein and also significantly decreases WDR87 expression and mislocalization, indicating CFAP47 is required for WDR87 transport during flagella biogenesis.\",\n      \"method\": \"Immunofluorescence staining (subcellular localization during spermatogenesis), co-immunoprecipitation / protein interaction assay (WDR87–CFAP47 interaction), immunoblotting in patient spermatozoa with CFAP47 mutations\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — reciprocal interaction shown, localization with functional consequence established, patient validation with two orthogonal methods (IF + immunoblot), single lab\",\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 DNA element, detected by DNA affinity purification followed by mass spectrometry in three cell lines (HEK, U87, HeLa), suggesting a role in chromatin regulatory complex assembly at Polycomb/Trithorax responsive elements.\",\n      \"method\": \"DNA affinity purification followed by mass spectrometry (three biological replicates in three cell lines)\",\n      \"journal\": \"Biochimica et biophysica acta. Gene regulatory mechanisms\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, DNA pulldown/MS without functional validation specific to WDR87; WDR87 is a minor finding in a paper focused on MLL/EZH2 biology\",\n      \"pmids\": [\"27932267\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Biallelic inactivating mutation in WDR87 was identified in a family with non-syndromic pediatric cataract, implicating WDR87 loss-of-function in lens development; iSyTE developmental lens expression analysis corroborated its expression in the lens.\",\n      \"method\": \"Whole-exome sequencing with homozygous truncating mutation identification; iSyTE lens expression database corroboration\",\n      \"journal\": \"Human genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — genetic association in a single family with computational expression support, no direct functional/mechanistic experiment performed on WDR87\",\n      \"pmids\": [\"27878435\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"WDR87 is a WD40-repeat domain protein that localizes to the middle piece of the sperm tail flagellum and physically interacts with CFAP47 to form a complex required for spermatozoa tail assembly; CFAP47 is additionally required for proper WDR87 transport during flagella biogenesis, and biallelic loss-of-function mutations in WDR87 are associated with non-syndromic pediatric cataract in humans.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"WDR87 is a WD40-repeat protein implicated in flagellar (sperm tail) assembly during spermiogenesis [#0]. It localizes to the middle piece of the spermatozoa tail and physically interacts with the cilia- and flagella-associated protein CFAP47 to form a complex required for sperm tail assembly; during spermiogenesis WDR87 migrates from perinuclear cytoplasm through the manchette to the tail middle piece, and CFAP47 is required for its proper transport, since patient CFAP47 loss-of-function reduces and mislocalizes WDR87 [#0]. Beyond this flagellar role, no further mechanistic detail on WDR87's biochemical activity has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"An initial association linked WDR87 loss-of-function to a human developmental phenotype, raising the question of where WDR87 acts in vivo.\",\n      \"evidence\": \"Whole-exome sequencing identifying a biallelic truncating mutation in a single non-syndromic pediatric cataract family, with iSyTE lens expression corroboration\",\n      \"pmids\": [\"27878435\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single family with no functional or rescue experiment on WDR87\", \"No mechanism connecting WDR87 to lens biology established\", \"Genetic association only, causality not demonstrated\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"A proteomic screen placed WDR87 at a chromatin cis-regulatory element, hinting at a possible nuclear/regulatory association, though without WDR87-specific validation.\",\n      \"evidence\": \"DNA affinity purification followed by mass spectrometry at the PRE-PIK3C2B element across three cell lines\",\n      \"pmids\": [\"27932267\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No functional validation specific to WDR87\", \"WDR87 was a minor finding in a paper centered on MLL/EZH2 biology\", \"DNA binding not demonstrated to be direct\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Establishing WDR87's molecular partner and subcellular itinerary defined its function in sperm tail assembly, answering what cellular process WDR87 contributes to.\",\n      \"evidence\": \"Immunofluorescence localization across spermatogenesis, co-immunoprecipitation of WDR87 with CFAP47, and immunoblotting in CFAP47-mutant patient spermatozoa\",\n      \"pmids\": [\"36571501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab; interaction not yet reconstituted with purified components\", \"Catalytic or structural role of WDR87 within the complex undefined\", \"Connection between the flagellar role and the earlier cataract/chromatin observations unexplained\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of WDR87 and how it reconciles its sperm flagellar role with the reported lens phenotype remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No defined enzymatic or scaffolding activity\", \"No structural model of the WDR87-CFAP47 complex\", \"No mechanism linking WDR87 to lens development\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"CFAP47\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":2,"faith_pct":50.0}}