{"gene":"NOPCHAP1","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2021,"finding":"NOPCHAP1 (C12ORF45) acts as a PAQosome cofactor and client-loading bridge between NOP58 and the PAQosome complex: it makes direct physical interactions with the CC-NOP domain of NOP58 and with domain II of RUVBL1/2 AAA+ ATPases, selectively loading NOP58 (but not the closely related CC-NOP proteins NOP56 or PRPF31) onto the PAQosome to promote box C/D snoRNP biogenesis.","method":"NOP58 mutant analysis, proteomic/co-immunoprecipitation experiments, identification of assembly intermediates, NOPCHAP1 KO cell lines with expression readouts","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal pulldowns, mutagenesis of NOP58 domains, KO cell phenotype, and multiple orthogonal proteomic methods in a single focused study","pmids":["33367824"],"is_preprint":false},{"year":2021,"finding":"NOPCHAP1 interaction with RUVBL1/2 is disrupted upon ATP binding, indicating the NOPCHAP1–RUVBL1/2 interaction is nucleotide-state dependent.","method":"Biochemical/proteomic binding assays with ATP treatment","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay with ATP perturbation, single lab, single study","pmids":["33367824"],"is_preprint":false},{"year":2021,"finding":"NOP58 protein expression, but not NOP56 or PRPF31 expression, is decreased in NOPCHAP1 KO cells, demonstrating that NOPCHAP1 is specifically required for NOP58 stability/assembly.","method":"NOPCHAP1 KO cell lines with protein expression analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined molecular phenotype, single lab, single study","pmids":["33367824"],"is_preprint":false}],"current_model":"NOPCHAP1 is a PAQosome cofactor that selectively bridges the core snoRNP protein NOP58 (via its CC-NOP domain) to the RUVBL1/2 AAA+ ATPases (via their domain II) in a nucleotide-state-dependent manner, thereby specifically chaperoning NOP58 loading onto the PAQosome to promote box C/D snoRNP biogenesis; loss of NOPCHAP1 reduces NOP58 but not the closely related NOP56 or PRPF31 proteins."},"narrative":{"mechanistic_narrative":"NOPCHAP1 (C12ORF45) is a PAQosome cofactor that functions as a client-loading bridge to promote box C/D snoRNP biogenesis [PMID:33367824]. It makes direct physical contacts with the CC-NOP domain of the core snoRNP protein NOP58 and with domain II of the RUVBL1/2 AAA+ ATPases, selectively loading NOP58—but not the closely related CC-NOP proteins NOP56 or PRPF31—onto the PAQosome [PMID:33367824]. The NOPCHAP1–RUVBL1/2 interaction is nucleotide-state dependent, being disrupted upon ATP binding, which couples client handoff to the ATPase cycle of the RUVBL machinery [PMID:33367824]. Consistent with a dedicated chaperoning role, loss of NOPCHAP1 specifically reduces NOP58 protein levels while leaving NOP56 and PRPF31 unaffected [PMID:33367824]. Beyond this PAQosome-linked client-loading function, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Established that NOPCHAP1 is a PAQosome cofactor that physically bridges NOP58 to the RUVBL1/2 ATPases, answering how a specific box C/D snoRNP client is delivered to the PAQosome assembly machinery.","evidence":"NOP58 domain mutagenesis, reciprocal co-immunoprecipitation/proteomics, assembly-intermediate identification, and KO cell readouts","pmids":["33367824"],"confidence":"High","gaps":["No structural model of the NOPCHAP1–NOP58–RUVBL1/2 ternary assembly","Mechanism distinguishing NOP58 from NOP56/PRPF31 at the molecular level not resolved","Stoichiometry and dynamics of client release onto the mature snoRNP not defined"]},{"year":2021,"claim":"Showed the NOPCHAP1–RUVBL1/2 interaction is abolished by ATP binding, linking client handoff to the nucleotide cycle of the RUVBL ATPases.","evidence":"Biochemical/proteomic binding assays with ATP perturbation","pmids":["33367824"],"confidence":"Medium","gaps":["Single lab, single study; not independently confirmed","Whether ATP hydrolysis versus binding alone drives release is not separated","Kinetics of the nucleotide-dependent dissociation unmeasured"]},{"year":2021,"claim":"Demonstrated that NOPCHAP1 is specifically required for NOP58 stability/assembly, establishing a functional consequence of the chaperoning activity.","evidence":"NOPCHAP1 KO cell lines with protein expression analysis of NOP58, NOP56, and PRPF31","pmids":["33367824"],"confidence":"Medium","gaps":["Single KO study, single lab","Whether reduced NOP58 reflects degradation versus failed assembly not distinguished","Downstream impact on snoRNA modification activity and ribosome biogenesis not quantified"]},{"year":null,"claim":"How NOPCHAP1 achieves selectivity for NOP58 over other CC-NOP proteins, and the structural basis of the bridging interaction, remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of the complex","No defined recognition determinants beyond the CC-NOP domain","Physiological/organismal role of NOPCHAP1 loss uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]},{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0]}],"complexes":["PAQosome"],"partners":["NOP58","RUVBL1","RUVBL2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N5I9","full_name":"NOP protein chaperone 1","aliases":[],"length_aa":185,"mass_kda":20.1,"function":"Client-loading PAQosome/R2TP complex cofactor that selects NOP58 to promote box C/D small nucleolar ribonucleoprotein (snoRNP) assembly. Acts as a bridge between NOP58 and the R2TP complex via RUVBL1:RUVBL2","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8N5I9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NOPCHAP1","classification":"Common Essential","n_dependent_lines":886,"n_total_lines":1208,"dependency_fraction":0.7334437086092715},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"KPNB1","stoichiometry":0.2},{"gene":"NOP58","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NOPCHAP1","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Nuclear membrane","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NOPCHAP1"},"hgnc":{"alias_symbol":["MGC40397","DDSR1"],"prev_symbol":["C12orf45"]},"alphafold":{"accession":"Q8N5I9","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5I9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5I9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N5I9-F1-predicted_aligned_error_v6.png","plddt_mean":70.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NOPCHAP1","jax_strain_url":"https://www.jax.org/strain/search?query=NOPCHAP1"},"sequence":{"accession":"Q8N5I9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N5I9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N5I9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N5I9"}},"corpus_meta":[{"pmid":"26412854","id":"PMC_26412854","title":"A BRCA1-interacting lncRNA regulates homologous recombination.","date":"2015","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/26412854","citation_count":128,"is_preprint":false},{"pmid":"33367824","id":"PMC_33367824","title":"NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis.","date":"2021","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/33367824","citation_count":20,"is_preprint":false},{"pmid":"26420434","id":"PMC_26420434","title":"A lncRNA to repair DNA.","date":"2015","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/26420434","citation_count":18,"is_preprint":false},{"pmid":"40341079","id":"PMC_40341079","title":"Unveiling the role of TCF19 in intervertebral disc degeneration with single-cell and bulk RNA sequencing.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40341079","citation_count":1,"is_preprint":false},{"pmid":"39014289","id":"PMC_39014289","title":"Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.","date":"2024","source":"Reproductive sciences (Thousand Oaks, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/39014289","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4186,"output_tokens":797,"usd":0.012257,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7205,"output_tokens":1582,"usd":0.037788,"stage2_stop_reason":"end_turn"},"total_usd":0.050045,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"NOPCHAP1 (C12ORF45) acts as a PAQosome cofactor and client-loading bridge between NOP58 and the PAQosome complex: it makes direct physical interactions with the CC-NOP domain of NOP58 and with domain II of RUVBL1/2 AAA+ ATPases, selectively loading NOP58 (but not the closely related CC-NOP proteins NOP56 or PRPF31) onto the PAQosome to promote box C/D snoRNP biogenesis.\",\n      \"method\": \"NOP58 mutant analysis, proteomic/co-immunoprecipitation experiments, identification of assembly intermediates, NOPCHAP1 KO cell lines with expression readouts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal pulldowns, mutagenesis of NOP58 domains, KO cell phenotype, and multiple orthogonal proteomic methods in a single focused study\",\n      \"pmids\": [\"33367824\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NOPCHAP1 interaction with RUVBL1/2 is disrupted upon ATP binding, indicating the NOPCHAP1–RUVBL1/2 interaction is nucleotide-state dependent.\",\n      \"method\": \"Biochemical/proteomic binding assays with ATP treatment\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay with ATP perturbation, single lab, single study\",\n      \"pmids\": [\"33367824\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NOP58 protein expression, but not NOP56 or PRPF31 expression, is decreased in NOPCHAP1 KO cells, demonstrating that NOPCHAP1 is specifically required for NOP58 stability/assembly.\",\n      \"method\": \"NOPCHAP1 KO cell lines with protein expression analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined molecular phenotype, single lab, single study\",\n      \"pmids\": [\"33367824\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NOPCHAP1 is a PAQosome cofactor that selectively bridges the core snoRNP protein NOP58 (via its CC-NOP domain) to the RUVBL1/2 AAA+ ATPases (via their domain II) in a nucleotide-state-dependent manner, thereby specifically chaperoning NOP58 loading onto the PAQosome to promote box C/D snoRNP biogenesis; loss of NOPCHAP1 reduces NOP58 but not the closely related NOP56 or PRPF31 proteins.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NOPCHAP1 (C12ORF45) is a PAQosome cofactor that functions as a client-loading bridge to promote box C/D snoRNP biogenesis [#0]. It makes direct physical contacts with the CC-NOP domain of the core snoRNP protein NOP58 and with domain II of the RUVBL1/2 AAA+ ATPases, selectively loading NOP58—but not the closely related CC-NOP proteins NOP56 or PRPF31—onto the PAQosome [#0]. The NOPCHAP1–RUVBL1/2 interaction is nucleotide-state dependent, being disrupted upon ATP binding, which couples client handoff to the ATPase cycle of the RUVBL machinery [#1]. Consistent with a dedicated chaperoning role, loss of NOPCHAP1 specifically reduces NOP58 protein levels while leaving NOP56 and PRPF31 unaffected [#2]. Beyond this PAQosome-linked client-loading function, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Established that NOPCHAP1 is a PAQosome cofactor that physically bridges NOP58 to the RUVBL1/2 ATPases, answering how a specific box C/D snoRNP client is delivered to the PAQosome assembly machinery.\",\n      \"evidence\": \"NOP58 domain mutagenesis, reciprocal co-immunoprecipitation/proteomics, assembly-intermediate identification, and KO cell readouts\",\n      \"pmids\": [\"33367824\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the NOPCHAP1–NOP58–RUVBL1/2 ternary assembly\",\n        \"Mechanism distinguishing NOP58 from NOP56/PRPF31 at the molecular level not resolved\",\n        \"Stoichiometry and dynamics of client release onto the mature snoRNP not defined\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Showed the NOPCHAP1–RUVBL1/2 interaction is abolished by ATP binding, linking client handoff to the nucleotide cycle of the RUVBL ATPases.\",\n      \"evidence\": \"Biochemical/proteomic binding assays with ATP perturbation\",\n      \"pmids\": [\"33367824\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study; not independently confirmed\",\n        \"Whether ATP hydrolysis versus binding alone drives release is not separated\",\n        \"Kinetics of the nucleotide-dependent dissociation unmeasured\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Demonstrated that NOPCHAP1 is specifically required for NOP58 stability/assembly, establishing a functional consequence of the chaperoning activity.\",\n      \"evidence\": \"NOPCHAP1 KO cell lines with protein expression analysis of NOP58, NOP56, and PRPF31\",\n      \"pmids\": [\"33367824\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single KO study, single lab\",\n        \"Whether reduced NOP58 reflects degradation versus failed assembly not distinguished\",\n        \"Downstream impact on snoRNA modification activity and ribosome biogenesis not quantified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NOPCHAP1 achieves selectivity for NOP58 over other CC-NOP proteins, and the structural basis of the bridging interaction, remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of the complex\",\n        \"No defined recognition determinants beyond the CC-NOP domain\",\n        \"Physiological/organismal role of NOPCHAP1 loss uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PAQosome\"],\n    \"partners\": [\"NOP58\", \"RUVBL1\", \"RUVBL2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}