{"gene":"MYCBPAP","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2002,"finding":"MYCBPAP (AMAP-1) was identified as a novel AMY-1 (c-Myc-binding protein)-binding protein via yeast two-hybrid screening of a human testis cDNA library; AMY-1 was shown to bind to and colocalize with AMAP-1 in human 293T and HeLa cells, and AMAP-1 is specifically and post-meiotically expressed in the testis.","method":"Yeast two-hybrid screening, co-localization in 293T/HeLa cells","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 — single lab, yeast two-hybrid plus colocalization, no in vitro reconstitution","pmids":["12151104"],"is_preprint":false},{"year":2021,"finding":"FAP147 (MYCBPAP ortholog in Chlamydomonas) is a component of the C2a projection of the ciliary central apparatus; fap70-1 mutant axonemes lack FAP147 (along with FAP65/CFAP65 and FAP70/CFAP70), and FAP65 and FAP147 co-immunoprecipitate with HA-tagged FAP70, placing MYCBPAP in a C2a projection complex with CFAP65 and CFAP70.","method":"Cryo-electron microscopy, mass spectrometry of fap70-1 mutant axonemes, co-immunoprecipitation with HA-tagged FAP70","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 — cryo-EM structural localization, reciprocal co-IP, and mutant loss-of-protein analysis converge on the same conclusion","pmids":["33988244"],"is_preprint":false},{"year":2020,"finding":"MYCBPAP mRNA and protein localize to motile ciliated cells in humans, as demonstrated by new localization experiments on this previously uncharacterized gene.","method":"mRNA/protein localization experiments in motile ciliated cell populations","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 — direct localization experiment but without functional consequence tested","pmids":["32616903"],"is_preprint":false},{"year":2024,"finding":"MYCBPAP is required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice; Mycbpap-knockout males are infertile with disrupted centrosome-nuclear envelope docking and abnormal flagellar biogenesis. Interactome analyses using transgenic tagged-MYCBPAP mice revealed binding partners including central apparatus proteins CFAP65 and CFAP70 (C2a projection components) and centrosome-associated protein CCP110.","method":"Knockout mouse generation, fertility assays, transgenic rescue, interactome/co-IP mass spectrometry","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — knockout with defined cellular phenotype, transgenic rescue, and interactome MS with orthogonal validation","pmids":["39092789"],"is_preprint":false},{"year":2024,"finding":"Homozygous deleterious MYCBPAP variants in humans and Mycbpap-knockout mice cause asthenoteratozoospermia through disrupted acrosome biogenesis and abnormally elongated manchette during spermiogenesis; endogenous co-immunoprecipitation/mass spectrometry revealed interactions of MYCBPAP with ribosome elimination-related protein ARMC3 and central apparatus proteins CFAP65 and CFAP70; proteomic analysis showed significant downregulation of spermatogenesis, acrosomal, and flagellar proteins in knockout testes.","method":"Whole-exome sequencing in patients, Mycbpap-knockout mouse model, proteomics, endogenous co-IP/mass spectrometry","journal":"Science China. Life sciences","confidence":"High","confidence_rationale":"Tier 2 — human genetics plus KO mouse with defined cellular phenotypes plus interactome MS; replicated C2a complex interactions from prior work","pmids":["39704931"],"is_preprint":false},{"year":2026,"finding":"In the Chlamydomonas C2a projection, FAP147 (MYCBPAP ortholog) interacts with FAP174 (MYCBP-1 ortholog) through its MYCBPAP domain (residues 129–639); in silico docking and molecular dynamics simulations identified key FAP174 C-terminal residues (G48, S49, P52, Y55, L79, Q80, V83) and MYCBPAP peptide regions (including p15, residues 350–379) as the interaction interface; alanine substitution of individual FAP174 residues retained binding, indicating the interaction depends on a broader interface rather than discrete amino acids.","method":"Overlay binding assay, in silico docking (CABS-Dock), molecular dynamics simulation, alanine mutagenesis","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"Medium","confidence_rationale":"Tier 3 — overlay assay and computational docking/MD; mutagenesis performed but no in vitro reconstitution or structural validation","pmids":["41724729"],"is_preprint":false},{"year":2023,"finding":"MYCBPAP protein is shuttled by bone marrow mesenchymal stem cell-derived exosomes; knockdown of MYCBPAP inhibited the protective effects of these exosomes on rat neuronal cells and exacerbated synaptic damage in stroke model rats, implicating MYCBPAP in synaptic remodeling downstream of exosome signaling.","method":"Exosome protein cargo identification, MYCBPAP knockdown rescue experiments in vitro and in vivo, Western blot, immunohistochemistry","journal":"Journal of chemical neuroanatomy","confidence":"Low","confidence_rationale":"Tier 3 — single lab, KD with phenotype but no defined molecular mechanism or pathway placement","pmids":["37423468"],"is_preprint":false}],"current_model":"MYCBPAP is a testis-enriched protein that localizes to the C2a projection of the ciliary/flagellar central apparatus, where it forms a complex with CFAP65, CFAP70, and (in Chlamydomonas) FAP174, and is required for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly; loss-of-function in mice and humans causes male infertility through asthenoteratozoospermia."},"narrative":{"teleology":[{"year":2002,"claim":"Identification of MYCBPAP as a testis-specific, post-meiotically expressed protein that binds the c-Myc-binding protein AMY-1 established it as a candidate spermatogenesis factor of unknown function.","evidence":"Yeast two-hybrid screen of human testis cDNA library with co-localization in 293T/HeLa cells","pmids":["12151104"],"confidence":"Medium","gaps":["Interaction validated only by yeast two-hybrid and co-localization, not by endogenous co-IP or reconstitution","No functional consequence of interaction tested","Molecular activity of MYCBPAP undefined"]},{"year":2020,"claim":"Localization of MYCBPAP mRNA and protein to motile ciliated cells extended its expression context beyond the testis and linked it to the motile cilia program.","evidence":"mRNA and protein localization in human motile ciliated cell populations","pmids":["32616903"],"confidence":"Medium","gaps":["No functional consequence of ciliary localization demonstrated","Whether MYCBPAP contributes to airway cilia function is untested"]},{"year":2021,"claim":"Structural and biochemical placement of the MYCBPAP ortholog FAP147 within the C2a projection of the Chlamydomonas central apparatus, in a complex with FAP65/CFAP65 and FAP70/CFAP70, defined its axonemal substructure and immediate molecular neighbors.","evidence":"Cryo-EM of wild-type and fap70-1 mutant axonemes, mass spectrometry, co-IP with HA-tagged FAP70","pmids":["33988244"],"confidence":"High","gaps":["C2a projection function in motility regulation not directly tested","Whether MYCBPAP is an enzymatic or purely structural component is unknown"]},{"year":2024,"claim":"Knockout studies in mice and identification of human loss-of-function variants established that MYCBPAP is essential for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, with loss causing asthenoteratozoospermia and male infertility; interactome analysis confirmed the conserved CFAP65/CFAP70 complex and identified new partners CCP110 and ARMC3.","evidence":"Mycbpap-knockout mouse with fertility and cellular phenotyping, transgenic rescue, whole-exome sequencing of infertile patients, endogenous co-IP/mass spectrometry, testis proteomics","pmids":["39092789","39704931"],"confidence":"High","gaps":["Enzymatic activity versus scaffolding role undetermined","How MYCBPAP coordinates centrosome–nuclear envelope docking mechanistically (e.g., via CCP110) is not resolved","Whether MYCBPAP loss causes primary ciliary dyskinesia phenotypes beyond infertility is untested"]},{"year":2026,"claim":"Mapping the interaction interface between the MYCBPAP domain and FAP174 in Chlamydomonas revealed a distributed binding surface rather than discrete hotspot residues, refining the structural basis of C2a projection assembly.","evidence":"Overlay binding assay, CABS-Dock in silico docking, molecular dynamics simulation, alanine scanning mutagenesis","pmids":["41724729"],"confidence":"Medium","gaps":["No high-resolution co-structure available","In vitro reconstitution of the full C2a subcomplex not performed","Whether FAP174/MYCBP-1 interaction is conserved in mammalian sperm flagella is untested"]},{"year":null,"claim":"Whether MYCBPAP possesses intrinsic catalytic activity or acts solely as a structural scaffold within the C2a projection and during spermiogenesis remains unresolved, and its potential role in motile cilia outside the testis (e.g., airway, ependymal) has not been functionally assessed.","evidence":"","pmids":[],"confidence":"Low","gaps":["No enzymatic activity tested","No structural model of mammalian MYCBPAP","Role in non-testicular motile cilia undefined"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,2,3]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,3]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,3,4]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[3,4]}],"complexes":["C2a projection complex (CFAP65–CFAP70–MYCBPAP)"],"partners":["CFAP65","CFAP70","CCP110","ARMC3","AMY1","FAP174"],"other_free_text":[]},"mechanistic_narrative":"MYCBPAP is a testis-enriched protein that functions as a structural component of the C2a projection of the motile ciliary/flagellar central apparatus, where it forms a complex with CFAP65, CFAP70, and the Chlamydomonas-specific subunit FAP174, contributing to axonemal architecture [PMID:33988244, PMID:39092789, PMID:41724729]. In spermiogenesis, MYCBPAP is required for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, interacting with the centrosomal protein CCP110 and the ribosome elimination-associated protein ARMC3 [PMID:39092789, PMID:39704931]. Loss-of-function mutations in MYCBPAP cause asthenoteratozoospermia and male infertility in both mice and humans [PMID:39092789, PMID:39704931]."},"prefetch_data":{"uniprot":{"accession":"Q8TBZ2","full_name":"MYCBP-associated protein","aliases":["AMAM-1","AMY-1-binding protein 1","AMAP-1"],"length_aa":984,"mass_kda":111.9,"function":"Plays a crucial role in centrosome-nuclear envelope docking during spermiogenesis, a key step for anchoring the centrosome to the nucleus that is essential for proper sperm flagellum biogenesis. Also required for acrosome biogenesis, manchette organization, and spermatid head morphogenesis, contributing to the complete and functional assembly of the sperm flagellum","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q8TBZ2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYCBPAP","classification":"Not Classified","n_dependent_lines":39,"n_total_lines":1208,"dependency_fraction":0.03228476821192053},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MYCBPAP","total_profiled":1310},"omim":[{"mim_id":"609835","title":"MYCBP-ASSOCIATED PROTEIN; MYCBPAP","url":"https://www.omim.org/entry/609835"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":61.7}],"url":"https://www.proteinatlas.org/search/MYCBPAP"},"hgnc":{"alias_symbol":["AMAP-1","DKFZp434N1415"],"prev_symbol":[]},"alphafold":{"accession":"Q8TBZ2","domains":[{"cath_id":"-","chopping":"232-260_268-354","consensus_level":"high","plddt":73.6184,"start":232,"end":354},{"cath_id":"2.60.40.10","chopping":"362-375_402-470_480-541","consensus_level":"high","plddt":81.6298,"start":362,"end":541}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TBZ2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TBZ2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TBZ2-F1-predicted_aligned_error_v6.png","plddt_mean":59.72},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYCBPAP","jax_strain_url":"https://www.jax.org/strain/search?query=MYCBPAP"},"sequence":{"accession":"Q8TBZ2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TBZ2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TBZ2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TBZ2"}},"corpus_meta":[{"pmid":"32616903","id":"PMC_32616903","title":"The transcriptional signature associated with human motile cilia.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32616903","citation_count":45,"is_preprint":false},{"pmid":"33988244","id":"PMC_33988244","title":"Chlamydomonas FAP70 is a component of the previously uncharacterized ciliary central apparatus projection C2a.","date":"2021","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/33988244","citation_count":18,"is_preprint":false},{"pmid":"12151104","id":"PMC_12151104","title":"AMAP-1, a novel testis-specific AMY-1-binding protein, is differentially expressed during the course of spermatogenesis.","date":"2002","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/12151104","citation_count":12,"is_preprint":false},{"pmid":"37423468","id":"PMC_37423468","title":"Exosome-shuttled MYCBPAP from bone marrow mesenchymal stem cells regulates synaptic remodeling and ameliorates ischemic stroke in rats.","date":"2023","source":"Journal of chemical neuroanatomy","url":"https://pubmed.ncbi.nlm.nih.gov/37423468","citation_count":8,"is_preprint":false},{"pmid":"39092789","id":"PMC_39092789","title":"MYCBPAP is a central apparatus protein required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice.","date":"2024","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/39092789","citation_count":3,"is_preprint":false},{"pmid":"39704931","id":"PMC_39704931","title":"Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.","date":"2024","source":"Science China. Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39704931","citation_count":2,"is_preprint":false},{"pmid":"41504506","id":"PMC_41504506","title":"Genetic correlations among diaphragmatic, femoral, inguinal, ventral, and umbilical hernias and identification of their candidate genes.","date":"2026","source":"International journal of surgery (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/41504506","citation_count":1,"is_preprint":false},{"pmid":"41724729","id":"PMC_41724729","title":"Domain-Level Interaction of FAP174 (MYCBP-1) and FAP147 (MYCBPAP) Proteins of the C2a Projection of Chlamydomonas Cilia.","date":"2026","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/41724729","citation_count":0,"is_preprint":false},{"pmid":"40979936","id":"PMC_40979936","title":"Identification of Specific LncRNA Markers in Severe Tuberculosis for Early Diagnosis.","date":"2025","source":"Infection and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/40979936","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6063,"output_tokens":1857,"usd":0.023022},"stage2":{"model":"claude-opus-4-6","input_tokens":5122,"output_tokens":1658,"usd":0.10059},"total_usd":0.123612,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"MYCBPAP (AMAP-1) was identified as a novel AMY-1 (c-Myc-binding protein)-binding protein via yeast two-hybrid screening of a human testis cDNA library; AMY-1 was shown to bind to and colocalize with AMAP-1 in human 293T and HeLa cells, and AMAP-1 is specifically and post-meiotically expressed in the testis.\",\n      \"method\": \"Yeast two-hybrid screening, co-localization in 293T/HeLa cells\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, yeast two-hybrid plus colocalization, no in vitro reconstitution\",\n      \"pmids\": [\"12151104\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FAP147 (MYCBPAP ortholog in Chlamydomonas) is a component of the C2a projection of the ciliary central apparatus; fap70-1 mutant axonemes lack FAP147 (along with FAP65/CFAP65 and FAP70/CFAP70), and FAP65 and FAP147 co-immunoprecipitate with HA-tagged FAP70, placing MYCBPAP in a C2a projection complex with CFAP65 and CFAP70.\",\n      \"method\": \"Cryo-electron microscopy, mass spectrometry of fap70-1 mutant axonemes, co-immunoprecipitation with HA-tagged FAP70\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — cryo-EM structural localization, reciprocal co-IP, and mutant loss-of-protein analysis converge on the same conclusion\",\n      \"pmids\": [\"33988244\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MYCBPAP mRNA and protein localize to motile ciliated cells in humans, as demonstrated by new localization experiments on this previously uncharacterized gene.\",\n      \"method\": \"mRNA/protein localization experiments in motile ciliated cell populations\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — direct localization experiment but without functional consequence tested\",\n      \"pmids\": [\"32616903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MYCBPAP is required for centrosome-nuclear envelope docking and sperm tail biogenesis in mice; Mycbpap-knockout males are infertile with disrupted centrosome-nuclear envelope docking and abnormal flagellar biogenesis. Interactome analyses using transgenic tagged-MYCBPAP mice revealed binding partners including central apparatus proteins CFAP65 and CFAP70 (C2a projection components) and centrosome-associated protein CCP110.\",\n      \"method\": \"Knockout mouse generation, fertility assays, transgenic rescue, interactome/co-IP mass spectrometry\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — knockout with defined cellular phenotype, transgenic rescue, and interactome MS with orthogonal validation\",\n      \"pmids\": [\"39092789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Homozygous deleterious MYCBPAP variants in humans and Mycbpap-knockout mice cause asthenoteratozoospermia through disrupted acrosome biogenesis and abnormally elongated manchette during spermiogenesis; endogenous co-immunoprecipitation/mass spectrometry revealed interactions of MYCBPAP with ribosome elimination-related protein ARMC3 and central apparatus proteins CFAP65 and CFAP70; proteomic analysis showed significant downregulation of spermatogenesis, acrosomal, and flagellar proteins in knockout testes.\",\n      \"method\": \"Whole-exome sequencing in patients, Mycbpap-knockout mouse model, proteomics, endogenous co-IP/mass spectrometry\",\n      \"journal\": \"Science China. Life sciences\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — human genetics plus KO mouse with defined cellular phenotypes plus interactome MS; replicated C2a complex interactions from prior work\",\n      \"pmids\": [\"39704931\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In the Chlamydomonas C2a projection, FAP147 (MYCBPAP ortholog) interacts with FAP174 (MYCBP-1 ortholog) through its MYCBPAP domain (residues 129–639); in silico docking and molecular dynamics simulations identified key FAP174 C-terminal residues (G48, S49, P52, Y55, L79, Q80, V83) and MYCBPAP peptide regions (including p15, residues 350–379) as the interaction interface; alanine substitution of individual FAP174 residues retained binding, indicating the interaction depends on a broader interface rather than discrete amino acids.\",\n      \"method\": \"Overlay binding assay, in silico docking (CABS-Dock), molecular dynamics simulation, alanine mutagenesis\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — overlay assay and computational docking/MD; mutagenesis performed but no in vitro reconstitution or structural validation\",\n      \"pmids\": [\"41724729\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MYCBPAP protein is shuttled by bone marrow mesenchymal stem cell-derived exosomes; knockdown of MYCBPAP inhibited the protective effects of these exosomes on rat neuronal cells and exacerbated synaptic damage in stroke model rats, implicating MYCBPAP in synaptic remodeling downstream of exosome signaling.\",\n      \"method\": \"Exosome protein cargo identification, MYCBPAP knockdown rescue experiments in vitro and in vivo, Western blot, immunohistochemistry\",\n      \"journal\": \"Journal of chemical neuroanatomy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, KD with phenotype but no defined molecular mechanism or pathway placement\",\n      \"pmids\": [\"37423468\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYCBPAP is a testis-enriched protein that localizes to the C2a projection of the ciliary/flagellar central apparatus, where it forms a complex with CFAP65, CFAP70, and (in Chlamydomonas) FAP174, and is required for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly; loss-of-function in mice and humans causes male infertility through asthenoteratozoospermia.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MYCBPAP is a testis-enriched protein that functions as a structural component of the C2a projection of the motile ciliary/flagellar central apparatus, where it forms a complex with CFAP65, CFAP70, and the Chlamydomonas-specific subunit FAP174, contributing to axonemal architecture [PMID:33988244, PMID:39092789, PMID:41724729]. In spermiogenesis, MYCBPAP is required for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, interacting with the centrosomal protein CCP110 and the ribosome elimination-associated protein ARMC3 [PMID:39092789, PMID:39704931]. Loss-of-function mutations in MYCBPAP cause asthenoteratozoospermia and male infertility in both mice and humans [PMID:39092789, PMID:39704931].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Identification of MYCBPAP as a testis-specific, post-meiotically expressed protein that binds the c-Myc-binding protein AMY-1 established it as a candidate spermatogenesis factor of unknown function.\",\n      \"evidence\": \"Yeast two-hybrid screen of human testis cDNA library with co-localization in 293T/HeLa cells\",\n      \"pmids\": [\"12151104\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction validated only by yeast two-hybrid and co-localization, not by endogenous co-IP or reconstitution\", \"No functional consequence of interaction tested\", \"Molecular activity of MYCBPAP undefined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Localization of MYCBPAP mRNA and protein to motile ciliated cells extended its expression context beyond the testis and linked it to the motile cilia program.\",\n      \"evidence\": \"mRNA and protein localization in human motile ciliated cell populations\",\n      \"pmids\": [\"32616903\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional consequence of ciliary localization demonstrated\", \"Whether MYCBPAP contributes to airway cilia function is untested\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Structural and biochemical placement of the MYCBPAP ortholog FAP147 within the C2a projection of the Chlamydomonas central apparatus, in a complex with FAP65/CFAP65 and FAP70/CFAP70, defined its axonemal substructure and immediate molecular neighbors.\",\n      \"evidence\": \"Cryo-EM of wild-type and fap70-1 mutant axonemes, mass spectrometry, co-IP with HA-tagged FAP70\",\n      \"pmids\": [\"33988244\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"C2a projection function in motility regulation not directly tested\", \"Whether MYCBPAP is an enzymatic or purely structural component is unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Knockout studies in mice and identification of human loss-of-function variants established that MYCBPAP is essential for centrosome–nuclear envelope docking, acrosome biogenesis, manchette organization, and sperm tail assembly, with loss causing asthenoteratozoospermia and male infertility; interactome analysis confirmed the conserved CFAP65/CFAP70 complex and identified new partners CCP110 and ARMC3.\",\n      \"evidence\": \"Mycbpap-knockout mouse with fertility and cellular phenotyping, transgenic rescue, whole-exome sequencing of infertile patients, endogenous co-IP/mass spectrometry, testis proteomics\",\n      \"pmids\": [\"39092789\", \"39704931\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Enzymatic activity versus scaffolding role undetermined\", \"How MYCBPAP coordinates centrosome–nuclear envelope docking mechanistically (e.g., via CCP110) is not resolved\", \"Whether MYCBPAP loss causes primary ciliary dyskinesia phenotypes beyond infertility is untested\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Mapping the interaction interface between the MYCBPAP domain and FAP174 in Chlamydomonas revealed a distributed binding surface rather than discrete hotspot residues, refining the structural basis of C2a projection assembly.\",\n      \"evidence\": \"Overlay binding assay, CABS-Dock in silico docking, molecular dynamics simulation, alanine scanning mutagenesis\",\n      \"pmids\": [\"41724729\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution co-structure available\", \"In vitro reconstitution of the full C2a subcomplex not performed\", \"Whether FAP174/MYCBP-1 interaction is conserved in mammalian sperm flagella is untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether MYCBPAP possesses intrinsic catalytic activity or acts solely as a structural scaffold within the C2a projection and during spermiogenesis remains unresolved, and its potential role in motile cilia outside the testis (e.g., airway, ependymal) has not been functionally assessed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No enzymatic activity tested\", \"No structural model of mammalian MYCBPAP\", \"Role in non-testicular motile cilia undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 3, 4]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\n      \"C2a projection complex (CFAP65–CFAP70–MYCBPAP)\"\n    ],\n    \"partners\": [\n      \"CFAP65\",\n      \"CFAP70\",\n      \"CCP110\",\n      \"ARMC3\",\n      \"AMY1\",\n      \"FAP174\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}