{"gene":"ANKRD40","run_date":"2026-06-09T22:02:43","timeline":{"discoveries":[{"year":2025,"finding":"ANKRD40 was identified as a component of MZF1 nuclear bodies (MZF1-NBs), implicated in protein folding functions within these intranuclear structures, based on proteomic and protein-protein interaction (interactome) analysis.","method":"Proteomic interactome analysis / protein-protein interaction analysis of MZF1 nuclear bodies","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (proteomic/interactome listing), no functional validation of ANKRD40's specific role in protein folding or nuclear bodies","pmids":["39954358"],"is_preprint":false}],"current_model":"ANKRD40 has been identified as a binding partner within MZF1 nuclear bodies via interactome analysis, with a proposed role in protein folding, but no direct mechanistic studies have established its enzymatic activity, substrates, or defined pathway position."},"narrative":{"mechanistic_narrative":"ANKRD40 was identified as a component of MZF1 nuclear bodies (MZF1-NBs) through proteomic interactome analysis of these intranuclear structures, where it has been associated with protein folding functions [PMID:39954358]. Beyond this single interactome-based association, no direct experimental evidence in the available corpus has established ANKRD40's enzymatic activity, substrates, recruitment mechanism, or defined pathway position.","teleology":[{"year":2025,"claim":"Whether ANKRD40 participates in any defined intranuclear assembly was unknown; interactome profiling placed it within MZF1 nuclear bodies and linked it to protein folding functions there.","evidence":"Proteomic interactome analysis of MZF1 nuclear bodies in cells","pmids":["39954358"],"confidence":"Low","gaps":["Single lab, single method (interactome listing) without functional validation of ANKRD40's role","No reciprocal or direct binding assay confirming the MZF1 interaction","The proposed protein folding function is inferred, not demonstrated for ANKRD40"]},{"year":null,"claim":"The molecular activity, direct binding partners, substrates, and pathway context of ANKRD40 remain uncharacterized.","evidence":"No further direct experimental evidence in the available corpus","pmids":[],"confidence":"Low","gaps":["No enzymatic or biochemical activity established","No structural model or domain function validated","Mechanism of recruitment to MZF1 nuclear bodies unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6AI12","full_name":"Ankyrin repeat domain-containing protein 40","aliases":[],"length_aa":368,"mass_kda":41.1,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6AI12/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ANKRD40","classification":"Not Classified","n_dependent_lines":40,"n_total_lines":1208,"dependency_fraction":0.033112582781456956},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000154945","cell_line_id":"CID001389","localizations":[{"compartment":"golgi","grade":3},{"compartment":"cytoplasmic","grade":1},{"compartment":"vesicles","grade":1}],"interactors":[{"gene":"AHCY","stoichiometry":0.2},{"gene":"EP400","stoichiometry":0.2},{"gene":"C2ORF44","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001389","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Nucleoli fibrillar center","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":196.0}],"url":"https://www.proteinatlas.org/search/ANKRD40"},"hgnc":{"alias_symbol":["MGC15396"],"prev_symbol":[]},"alphafold":{"accession":"Q6AI12","domains":[{"cath_id":"1.25.40.20","chopping":"1-97","consensus_level":"medium","plddt":93.4931,"start":1,"end":97},{"cath_id":"3.10.20.90","chopping":"259-340","consensus_level":"high","plddt":89.3445,"start":259,"end":340}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6AI12","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6AI12-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6AI12-F1-predicted_aligned_error_v6.png","plddt_mean":68.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ANKRD40","jax_strain_url":"https://www.jax.org/strain/search?query=ANKRD40"},"sequence":{"accession":"Q6AI12","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6AI12.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6AI12/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6AI12"}},"corpus_meta":[{"pmid":"36466608","id":"PMC_36466608","title":"Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer's disease in a 5 × FAD mouse model.","date":"2022","source":"Frontiers in aging neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/36466608","citation_count":21,"is_preprint":false},{"pmid":"33096259","id":"PMC_33096259","title":"Single symbiotic cell transcriptome sequencing of coral.","date":"2020","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/33096259","citation_count":3,"is_preprint":false},{"pmid":"39954358","id":"PMC_39954358","title":"Discovery of myeloid zinc finger (MZF) 1 nuclear bodies.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39954358","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3993,"output_tokens":289,"usd":0.008157,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6496,"output_tokens":676,"usd":0.02469,"stage2_stop_reason":"end_turn"},"total_usd":0.032847,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"ANKRD40 was identified as a component of MZF1 nuclear bodies (MZF1-NBs), implicated in protein folding functions within these intranuclear structures, based on proteomic and protein-protein interaction (interactome) analysis.\",\n      \"method\": \"Proteomic interactome analysis / protein-protein interaction analysis of MZF1 nuclear bodies\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (proteomic/interactome listing), no functional validation of ANKRD40's specific role in protein folding or nuclear bodies\",\n      \"pmids\": [\"39954358\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ANKRD40 has been identified as a binding partner within MZF1 nuclear bodies via interactome analysis, with a proposed role in protein folding, but no direct mechanistic studies have established its enzymatic activity, substrates, or defined pathway position.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ANKRD40 was identified as a component of MZF1 nuclear bodies (MZF1-NBs) through proteomic interactome analysis of these intranuclear structures, where it has been associated with protein folding functions [#0]. Beyond this single interactome-based association, no direct experimental evidence in the available corpus has established ANKRD40's enzymatic activity, substrates, recruitment mechanism, or defined pathway position.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether ANKRD40 participates in any defined intranuclear assembly was unknown; interactome profiling placed it within MZF1 nuclear bodies and linked it to protein folding functions there.\",\n      \"evidence\": \"Proteomic interactome analysis of MZF1 nuclear bodies in cells\",\n      \"pmids\": [\"39954358\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single method (interactome listing) without functional validation of ANKRD40's role\",\n        \"No reciprocal or direct binding assay confirming the MZF1 interaction\",\n        \"The proposed protein folding function is inferred, not demonstrated for ANKRD40\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity, direct binding partners, substrates, and pathway context of ANKRD40 remain uncharacterized.\",\n      \"evidence\": \"No further direct experimental evidence in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic or biochemical activity established\",\n        \"No structural model or domain function validated\",\n        \"Mechanism of recruitment to MZF1 nuclear bodies unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":1,"faith_pct":100.0}}