{"gene":"C17ORF75","run_date":"2026-06-11T12:11:54","timeline":{"discoveries":[{"year":2022,"finding":"C17orf75 expression is regulated by the minor spliceosome component SCNM1 through U12 intron splicing; loss of SCNM1 (knockout or knockdown) severely reduces C17orf75 expression, and re-introduction of SCNM1 restores it.","method":"CRISPR-Cas9 knockout of SCNM1, siRNA knockdown, comparative transcriptome analysis, retroviral rescue in human fibroblasts and RPE-1 cells","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined molecular phenotype (reduced C17orf75 expression) and rescue experiment, but C17orf75 is one of several affected genes and its direct function was not characterized","pmids":["36084634"],"is_preprint":false},{"year":2022,"finding":"C17orf75 protein is downregulated in ZIP8-knockout human cells, placing it downstream of the metal cation transporter ZIP8 in a proteomic dependency relationship.","method":"CRISPR/Cas9 ZIP8 knockout, iTRAQ-based quantitative proteomics in human cells","journal":"Frontiers in molecular biosciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single proteomics screen, single lab, no functional follow-up on C17orf75 itself","pmids":["36330220"],"is_preprint":false}],"current_model":"C17orf75 is a protein whose expression depends on functional minor spliceosome activity (specifically SCNM1-mediated U12 intron splicing) and is also regulated downstream of the metal transporter ZIP8; no direct enzymatic activity, binding partners, or autonomous molecular function have been experimentally established for C17orf75 itself."},"narrative":{"mechanistic_narrative":"C17orf75 is a poorly characterized protein known primarily through its dependence on upstream regulatory inputs rather than any autonomous activity. Its expression requires functional minor spliceosome activity: loss of the U12 intron-splicing factor SCNM1 severely reduces C17orf75 expression, which is restored upon SCNM1 re-introduction, indicating that C17orf75 transcript maturation depends on minor spliceosome–mediated splicing [PMID:36084634]. No direct enzymatic activity, binding partners, substrates, or cellular function have been established for C17orf75 itself in the available corpus.","teleology":[{"year":2022,"claim":"Established that C17orf75 expression is governed by the minor spliceosome, identifying it as a downstream-regulated gene rather than characterizing its own function.","evidence":"CRISPR-Cas9 knockout and siRNA knockdown of SCNM1 with retroviral rescue and comparative transcriptome analysis in human fibroblasts and RPE-1 cells","pmids":["36084634"],"confidence":"Medium","gaps":["C17orf75 is one of several SCNM1-affected genes; its direct function was not characterized","no protein-level mechanism, partners, or activity defined for C17orf75","whether reduced C17orf75 contributes to any SCNM1-loss phenotype is unknown"]},{"year":2022,"claim":"Placed C17orf75 protein downstream of the metal cation transporter ZIP8 in a proteomic dependency, hinting at a connection to metal-transport-linked cellular state.","evidence":"CRISPR/Cas9 ZIP8 knockout with iTRAQ-based quantitative proteomics in human cells","pmids":["36330220"],"confidence":"Low","gaps":["single proteomics screen from one lab with no functional follow-up on C17orf75","mechanism linking ZIP8 to C17orf75 abundance unknown","direct versus indirect regulation not distinguished"]},{"year":null,"claim":"The autonomous molecular function of C17orf75 — its biochemical activity, localization, and physical partners — remains entirely undefined.","evidence":"no direct functional characterization in the available corpus","pmids":[],"confidence":"Low","gaps":["no enzymatic or binding activity established","no subcellular localization determined","no interaction partners or complex membership identified"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9HAS0","full_name":"Protein Njmu-R1","aliases":[],"length_aa":396,"mass_kda":44.6,"function":"As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). May have a role in spermatogenesis","subcellular_location":"Golgi apparatus, trans-Golgi network; Cytoplasmic vesicle","url":"https://www.uniprot.org/uniprotkb/Q9HAS0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/C17ORF75"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DRG1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/C17ORF75","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/C17ORF75"},"hgnc":{"alias_symbol":["NJMU-R1","SRI2"],"prev_symbol":[]},"alphafold":{"accession":"Q9HAS0","domains":[{"cath_id":"-","chopping":"38-45_73-135_147-184","consensus_level":"high","plddt":83.5723,"start":38,"end":184},{"cath_id":"-","chopping":"214-395","consensus_level":"medium","plddt":85.572,"start":214,"end":395}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HAS0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HAS0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HAS0-F1-predicted_aligned_error_v6.png","plddt_mean":76.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=C17ORF75","jax_strain_url":"https://www.jax.org/strain/search?query=C17ORF75"},"sequence":{"accession":"Q9HAS0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9HAS0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9HAS0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HAS0"}},"corpus_meta":[{"pmid":"10323787","id":"PMC_10323787","title":"CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta.","date":"1999","source":"Arteriosclerosis, thrombosis, and vascular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10323787","citation_count":147,"is_preprint":false},{"pmid":"37011095","id":"PMC_37011095","title":"Reconstruction of Solid Electrolyte Interphase with SrI2 Reactivates Dead Li for Durable Anode-Free Li-Metal Batteries.","date":"2023","source":"Angewandte Chemie (International ed. in English)","url":"https://pubmed.ncbi.nlm.nih.gov/37011095","citation_count":22,"is_preprint":false},{"pmid":"34821436","id":"PMC_34821436","title":"A novel immunodiagnosis panel for hepatocellular carcinoma based on bioinformatics and the autoantibody-antigen system.","date":"2021","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/34821436","citation_count":22,"is_preprint":false},{"pmid":"36084634","id":"PMC_36084634","title":"Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia.","date":"2022","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36084634","citation_count":14,"is_preprint":false},{"pmid":"23997030","id":"PMC_23997030","title":"Calcium phosphate cements with strontium halides as radiopacifiers.","date":"2013","source":"Journal of biomedical materials research. Part B, Applied biomaterials","url":"https://pubmed.ncbi.nlm.nih.gov/23997030","citation_count":10,"is_preprint":false},{"pmid":"36330220","id":"PMC_36330220","title":"Single-gene knockout-coupled omics analysis identifies C9orf85 and CXorf38 as two uncharacterized human proteins associated with ZIP8 malfunction.","date":"2022","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/36330220","citation_count":4,"is_preprint":false},{"pmid":"32830746","id":"PMC_32830746","title":"Developing new SrI2 and β-D-fructopyranose-based metal-organic frameworks with nonlinear optical properties.","date":"2019","source":"Acta crystallographica Section B, Structural science, crystal engineering and materials","url":"https://pubmed.ncbi.nlm.nih.gov/32830746","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6047,"output_tokens":533,"usd":0.013068,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6837,"output_tokens":1000,"usd":0.029593,"stage2_stop_reason":"end_turn"},"total_usd":0.042661,"stage1_batch_id":"msgbatch_01AsKq64opiyvpDv2j3FexYQ","stage2_batch_id":"msgbatch_01XG5TnAVxejxY779cwb2uS8","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"C17orf75 expression is regulated by the minor spliceosome component SCNM1 through U12 intron splicing; loss of SCNM1 (knockout or knockdown) severely reduces C17orf75 expression, and re-introduction of SCNM1 restores it.\",\n      \"method\": \"CRISPR-Cas9 knockout of SCNM1, siRNA knockdown, comparative transcriptome analysis, retroviral rescue in human fibroblasts and RPE-1 cells\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined molecular phenotype (reduced C17orf75 expression) and rescue experiment, but C17orf75 is one of several affected genes and its direct function was not characterized\",\n      \"pmids\": [\"36084634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"C17orf75 protein is downregulated in ZIP8-knockout human cells, placing it downstream of the metal cation transporter ZIP8 in a proteomic dependency relationship.\",\n      \"method\": \"CRISPR/Cas9 ZIP8 knockout, iTRAQ-based quantitative proteomics in human cells\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single proteomics screen, single lab, no functional follow-up on C17orf75 itself\",\n      \"pmids\": [\"36330220\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"C17orf75 is a protein whose expression depends on functional minor spliceosome activity (specifically SCNM1-mediated U12 intron splicing) and is also regulated downstream of the metal transporter ZIP8; no direct enzymatic activity, binding partners, or autonomous molecular function have been experimentally established for C17orf75 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"C17orf75 is a poorly characterized protein known primarily through its dependence on upstream regulatory inputs rather than any autonomous activity. Its expression requires functional minor spliceosome activity: loss of the U12 intron-splicing factor SCNM1 severely reduces C17orf75 expression, which is restored upon SCNM1 re-introduction, indicating that C17orf75 transcript maturation depends on minor spliceosome–mediated splicing [#0]. No direct enzymatic activity, binding partners, substrates, or cellular function have been established for C17orf75 itself in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"Established that C17orf75 expression is governed by the minor spliceosome, identifying it as a downstream-regulated gene rather than characterizing its own function.\",\n      \"evidence\": \"CRISPR-Cas9 knockout and siRNA knockdown of SCNM1 with retroviral rescue and comparative transcriptome analysis in human fibroblasts and RPE-1 cells\",\n      \"pmids\": [\"36084634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"C17orf75 is one of several SCNM1-affected genes; its direct function was not characterized\",\n        \"no protein-level mechanism, partners, or activity defined for C17orf75\",\n        \"whether reduced C17orf75 contributes to any SCNM1-loss phenotype is unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placed C17orf75 protein downstream of the metal cation transporter ZIP8 in a proteomic dependency, hinting at a connection to metal-transport-linked cellular state.\",\n      \"evidence\": \"CRISPR/Cas9 ZIP8 knockout with iTRAQ-based quantitative proteomics in human cells\",\n      \"pmids\": [\"36330220\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"single proteomics screen from one lab with no functional follow-up on C17orf75\",\n        \"mechanism linking ZIP8 to C17orf75 abundance unknown\",\n        \"direct versus indirect regulation not distinguished\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The autonomous molecular function of C17orf75 — its biochemical activity, localization, and physical partners — remains entirely undefined.\",\n      \"evidence\": \"no direct functional characterization in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no enzymatic or binding activity established\",\n        \"no subcellular localization determined\",\n        \"no interaction partners or complex membership identified\"\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":{"pairwise":"win","faith_supported":1,"faith_total":1,"faith_pct":100.0}}