{"gene":"C16ORF87","run_date":"2026-06-09T22:02:45","timeline":{"discoveries":[{"year":2026,"finding":"C16orf87 (proposed rename: HDIP) is a functional subunit of the MIER corepressor complex, mediating protein interactions between HDAC1 and MIER1. Homozygous knockout of C16orf87 in human cells alters chromatin accessibility and reduces cell migration, and impairs embryonic development in zebrafish.","method":"Co-immunoprecipitation/protein interaction assays to identify complex membership; CRISPR knockout with chromatin accessibility assay (ATAC-seq or equivalent) and cell migration assay; zebrafish knockout model for developmental phenotype","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal protein interaction data, KO with defined cellular and developmental phenotypes, multiple orthogonal readouts, single lab","pmids":["42062449"],"is_preprint":false},{"year":2026,"finding":"C16orf87 (renamed MHAP1) forms a stable complex with HDAC2 and MIER1, where the C-terminal IDR domain of HDAC2 promotes interactions with the ELM2 domain of MIER1 as well as the N- and C-termini of MHAP1. An integrative structural model of the HDAC1:MIER2:MHAP1 complex was built using experimental crosslinking data combined with computational modeling (I-TASSER, HADDOCK, AlphaFold).","method":"Crosslinking mass spectrometry combined with integrative computational structural modeling (I-TASSER, HADDOCK, AlphaFold) to map IDR-driven protein-protein interactions within the complex","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — crosslinking-MS with computational structural modeling, multiple orthogonal computational methods validated by experimental crosslinks, single lab, preprint","pmids":["41928988"],"is_preprint":true},{"year":2025,"finding":"C16ORF87 participates in an ARID5B-containing chromatin repressor complex together with MIER1, HDAC1, and HDAC2, which is tethered to active distal regulatory elements and promoters to repress genes involved in B cell proliferation and B cell-specific signaling.","method":"Proteomics (co-immunoprecipitation/mass spectrometry) to identify complex components; CUT&RUN to map genomic binding of ARID5B, HDAC1, and HDAC2; transcriptomics to identify repressed target genes","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — C16ORF87 identified as complex member by proteomics but mechanistic role of C16ORF87 itself not directly tested; preprint, single lab","pmids":["bio_10.1101_2025.10.17.683040"],"is_preprint":true}],"current_model":"C16orf87 (also called MHAP1 or HDIP) is a subunit of the MIER corepressor complex, where it bridges interactions between HDAC1/HDAC2 and MIER1 (via HDAC2's C-terminal IDR and MIER1's ELM2 domain); loss of C16orf87 alters chromatin accessibility, impairs cell migration in human cells, and disrupts embryonic development in zebrafish, consistent with its role in HDAC-mediated transcriptional repression at chromatin."},"narrative":{"mechanistic_narrative":"C16ORF87 (also designated MHAP1/HDIP) is a subunit of the MIER-type HDAC corepressor complex, where it functions as a protein-interaction bridge supporting HDAC-mediated transcriptional repression at chromatin [PMID:42062449]. Within the complex it associates with HDAC1/HDAC2 and MIER1, with HDAC2's C-terminal intrinsically disordered region promoting contacts to the ELM2 domain of MIER1 and to both the N- and C-termini of C16ORF87 [PMID:41928988]. Homozygous knockout in human cells alters chromatin accessibility and reduces cell migration, and loss of the gene impairs embryonic development in zebrafish, consistent with a role in chromatin-templated gene repression [PMID:42062449]. Beyond its role as a MIER/HDAC complex subunit, no additional independent biochemical activity for C16ORF87 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether C16ORF87 has any defined biochemical context was unknown; proteomic profiling placed it within an ARID5B-containing chromatin repressor complex, implicating it in transcriptional repression.","evidence":"Co-IP/mass spectrometry identifying complex members, CUT&RUN genomic mapping, and transcriptomics in a B cell system","pmids":["bio_10.1101_2025.10.17.683040"],"confidence":"Low","gaps":["C16ORF87's own mechanistic contribution was not directly tested — it was identified only as a co-purifying complex member","Preprint, single lab","Does not establish which residues or domains of C16ORF87 mediate complex association"]},{"year":2026,"claim":"It was unclear whether C16ORF87 is a functional rather than incidental complex subunit; reciprocal interaction assays plus loss-of-function established it as a bridging subunit of the MIER corepressor complex with cellular and developmental consequences.","evidence":"Co-IP/protein interaction assays for complex membership, CRISPR knockout with chromatin accessibility and migration assays in human cells, and a zebrafish knockout developmental model","pmids":["42062449"],"confidence":"Medium","gaps":["Direct molecular mechanism linking complex loss to altered chromatin accessibility not resolved","Specific gene targets driving the migration and developmental phenotypes not defined","Single lab"]},{"year":2026,"claim":"How C16ORF87 is physically wired into the complex was unknown; integrative structural modeling mapped IDR-driven contacts defining its interaction interfaces.","evidence":"Crosslinking mass spectrometry combined with integrative computational modeling (I-TASSER, HADDOCK, AlphaFold) (preprint)","pmids":["41928988"],"confidence":"Medium","gaps":["Structural model is computational, validated by crosslinks but lacking experimental high-resolution structure","Preprint, single lab","Functional importance of the mapped N- and C-terminal interfaces not tested by mutagenesis"]},{"year":null,"claim":"Whether C16ORF87 has any catalytic or chromatin-binding activity of its own, or acts purely as a scaffolding/bridging subunit, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No intrinsic enzymatic activity demonstrated","Mechanism by which the complex is recruited to specific loci is not attributed to C16ORF87","No high-resolution experimental structure of the complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,2]}],"complexes":["MIER corepressor complex"],"partners":["HDAC1","HDAC2","MIER1","ARID5B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6PH81","full_name":"UPF0547 protein C16orf87","aliases":[],"length_aa":154,"mass_kda":17.8,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q6PH81/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/C16ORF87"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HDAC1","stoichiometry":0.2},{"gene":"HDAC2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/C16ORF87","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":17.2}],"url":"https://www.proteinatlas.org/search/C16ORF87"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q6PH81","domains":[{"cath_id":"-","chopping":"10-46","consensus_level":"medium","plddt":88.3492,"start":10,"end":46}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PH81","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PH81-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PH81-F1-predicted_aligned_error_v6.png","plddt_mean":71.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=C16ORF87","jax_strain_url":"https://www.jax.org/strain/search?query=C16ORF87"},"sequence":{"accession":"Q6PH81","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6PH81.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6PH81/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PH81"}},"corpus_meta":[{"pmid":"41928988","id":"PMC_41928988","title":"Integrative Structural Modeling of Intrinsically Disordered Regions in a Human HDAC2 Chromatin Remodeling Complex.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41928988","citation_count":2,"is_preprint":false},{"pmid":"42062449","id":"PMC_42062449","title":"The C16orf87 protein is a subunit of the MIER corepressor complex controlling embryonic development and cell migration.","date":"2026","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/42062449","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.17.683040","title":"Leukemia Risk Factor ARID5B Coordinates HDAC-Mediated Transcriptional Repression","date":"2025-10-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.17.683040","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3387,"output_tokens":967,"usd":0.012333,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7418,"output_tokens":1582,"usd":0.03832,"stage2_stop_reason":"end_turn"},"total_usd":0.050653,"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\": 2026,\n      \"finding\": \"C16orf87 (proposed rename: HDIP) is a functional subunit of the MIER corepressor complex, mediating protein interactions between HDAC1 and MIER1. Homozygous knockout of C16orf87 in human cells alters chromatin accessibility and reduces cell migration, and impairs embryonic development in zebrafish.\",\n      \"method\": \"Co-immunoprecipitation/protein interaction assays to identify complex membership; CRISPR knockout with chromatin accessibility assay (ATAC-seq or equivalent) and cell migration assay; zebrafish knockout model for developmental phenotype\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal protein interaction data, KO with defined cellular and developmental phenotypes, multiple orthogonal readouts, single lab\",\n      \"pmids\": [\"42062449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"C16orf87 (renamed MHAP1) forms a stable complex with HDAC2 and MIER1, where the C-terminal IDR domain of HDAC2 promotes interactions with the ELM2 domain of MIER1 as well as the N- and C-termini of MHAP1. An integrative structural model of the HDAC1:MIER2:MHAP1 complex was built using experimental crosslinking data combined with computational modeling (I-TASSER, HADDOCK, AlphaFold).\",\n      \"method\": \"Crosslinking mass spectrometry combined with integrative computational structural modeling (I-TASSER, HADDOCK, AlphaFold) to map IDR-driven protein-protein interactions within the complex\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — crosslinking-MS with computational structural modeling, multiple orthogonal computational methods validated by experimental crosslinks, single lab, preprint\",\n      \"pmids\": [\"41928988\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"C16ORF87 participates in an ARID5B-containing chromatin repressor complex together with MIER1, HDAC1, and HDAC2, which is tethered to active distal regulatory elements and promoters to repress genes involved in B cell proliferation and B cell-specific signaling.\",\n      \"method\": \"Proteomics (co-immunoprecipitation/mass spectrometry) to identify complex components; CUT&RUN to map genomic binding of ARID5B, HDAC1, and HDAC2; transcriptomics to identify repressed target genes\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — C16ORF87 identified as complex member by proteomics but mechanistic role of C16ORF87 itself not directly tested; preprint, single lab\",\n      \"pmids\": [\"bio_10.1101_2025.10.17.683040\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"C16orf87 (also called MHAP1 or HDIP) is a subunit of the MIER corepressor complex, where it bridges interactions between HDAC1/HDAC2 and MIER1 (via HDAC2's C-terminal IDR and MIER1's ELM2 domain); loss of C16orf87 alters chromatin accessibility, impairs cell migration in human cells, and disrupts embryonic development in zebrafish, consistent with its role in HDAC-mediated transcriptional repression at chromatin.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"C16ORF87 (also designated MHAP1/HDIP) is a subunit of the MIER-type HDAC corepressor complex, where it functions as a protein-interaction bridge supporting HDAC-mediated transcriptional repression at chromatin [#0]. Within the complex it associates with HDAC1/HDAC2 and MIER1, with HDAC2's C-terminal intrinsically disordered region promoting contacts to the ELM2 domain of MIER1 and to both the N- and C-termini of C16ORF87 [#1]. Homozygous knockout in human cells alters chromatin accessibility and reduces cell migration, and loss of the gene impairs embryonic development in zebrafish, consistent with a role in chromatin-templated gene repression [#0]. Beyond its role as a MIER/HDAC complex subunit, no additional independent biochemical activity for C16ORF87 has been characterized in the available corpus.\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether C16ORF87 has any defined biochemical context was unknown; proteomic profiling placed it within an ARID5B-containing chromatin repressor complex, implicating it in transcriptional repression.\",\n      \"evidence\": \"Co-IP/mass spectrometry identifying complex members, CUT&RUN genomic mapping, and transcriptomics in a B cell system\",\n      \"pmids\": [\"bio_10.1101_2025.10.17.683040\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"C16ORF87's own mechanistic contribution was not directly tested — it was identified only as a co-purifying complex member\",\n        \"Preprint, single lab\",\n        \"Does not establish which residues or domains of C16ORF87 mediate complex association\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"It was unclear whether C16ORF87 is a functional rather than incidental complex subunit; reciprocal interaction assays plus loss-of-function established it as a bridging subunit of the MIER corepressor complex with cellular and developmental consequences.\",\n      \"evidence\": \"Co-IP/protein interaction assays for complex membership, CRISPR knockout with chromatin accessibility and migration assays in human cells, and a zebrafish knockout developmental model\",\n      \"pmids\": [\"42062449\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct molecular mechanism linking complex loss to altered chromatin accessibility not resolved\",\n        \"Specific gene targets driving the migration and developmental phenotypes not defined\",\n        \"Single lab\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"How C16ORF87 is physically wired into the complex was unknown; integrative structural modeling mapped IDR-driven contacts defining its interaction interfaces.\",\n      \"evidence\": \"Crosslinking mass spectrometry combined with integrative computational modeling (I-TASSER, HADDOCK, AlphaFold) (preprint)\",\n      \"pmids\": [\"41928988\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural model is computational, validated by crosslinks but lacking experimental high-resolution structure\",\n        \"Preprint, single lab\",\n        \"Functional importance of the mapped N- and C-terminal interfaces not tested by mutagenesis\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether C16ORF87 has any catalytic or chromatin-binding activity of its own, or acts purely as a scaffolding/bridging subunit, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No intrinsic enzymatic activity demonstrated\",\n        \"Mechanism by which the complex is recruited to specific loci is not attributed to C16ORF87\",\n        \"No high-resolution experimental structure of the complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\"MIER corepressor complex\"],\n    \"partners\": [\"HDAC1\", \"HDAC2\", \"MIER1\", \"ARID5B\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}