{"gene":"C19ORF25","run_date":"2026-06-09T22:02:45","timeline":{"discoveries":[{"year":2024,"finding":"Loss of C19orf25 enhances STING signaling; C19orf25 clustered with USE1 (a Golgi-to-ER transport protein) in a genome-wide optical pooled screen based on subcellular STING localization phenotypes, placing C19orf25 in a pathway involved in Golgi-to-ER retrograde transport that normally restrains STING signaling.","method":"Genome-wide optical pooled CRISPR screen with high-content subcellular imaging of STING localization in 45 million cells; phenotypic clustering; functional validation by measuring STING signaling upon gene loss","journal":"Cell systems","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen with imaging-based phenotyping and functional signaling readout, replicated in both preprint and peer-reviewed publication from same lab; no in vitro reconstitution or direct binding assay","pmids":["39657680","38645119"],"is_preprint":false}],"current_model":"C19orf25 is a gene of previously unknown function that co-clusters with USE1 (a Golgi-to-ER retrograde transport factor) and whose loss enhances STING innate immune signaling, suggesting it plays a role in Golgi-to-ER transport that normally limits STING activity."},"narrative":{"mechanistic_narrative":"C19orf25 is a functionally uncharacterized gene implicated in restraining STING-dependent innate immune signaling through a role in Golgi-to-ER retrograde transport [PMID:39657680, PMID:38645119]. In a genome-wide optical pooled CRISPR screen scoring subcellular STING localization, loss of C19orf25 enhanced STING signaling, and C19orf25 co-clustered phenotypically with USE1, a Golgi-to-ER retrograde transport factor, placing it in a transport pathway that normally limits STING activity [PMID:39657680, PMID:38645119]. Beyond this genetic and phenotypic association [PMID:39657680, PMID:38645119], no direct molecular activity, binding partner, or biochemical mechanism for C19orf25 has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Whether C19orf25 has any defined cellular role was unknown; a genome-wide imaging screen showed its loss enhances STING signaling and that it clusters with the retrograde transport factor USE1, establishing a candidate function in Golgi-to-ER transport that restrains STING.","evidence":"Genome-wide optical pooled CRISPR screen with high-content subcellular imaging of STING localization in 45 million cells, phenotypic clustering, and functional validation of STING signaling upon gene loss","pmids":["39657680","38645119"],"confidence":"Medium","gaps":["No direct physical interaction between C19orf25 and USE1 or other transport machinery demonstrated","No in vitro reconstitution or biochemical assay defining a molecular activity","Mechanism by which the implicated transport pathway restrains STING not resolved"]},{"year":null,"claim":"The molecular activity, direct binding partners, and subcellular localization of C19orf25, and the precise mechanism linking it to Golgi-to-ER transport and STING regulation, remain undefined.","evidence":"No further experimental characterization present in the available corpus","pmids":[],"confidence":"Medium","gaps":["No structural or biochemical characterization","No confirmed localization data","No reciprocal validation of the USE1 association"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UFG5","full_name":"UPF0449 protein C19orf25","aliases":[],"length_aa":118,"mass_kda":12.9,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q9UFG5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/C19ORF25"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"BNIP1","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/C19ORF25","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Intermediate filaments","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/C19ORF25"},"hgnc":{"alias_symbol":["FLJ36666"],"prev_symbol":[]},"alphafold":{"accession":"Q9UFG5","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UFG5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UFG5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UFG5-F1-predicted_aligned_error_v6.png","plddt_mean":83.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=C19ORF25","jax_strain_url":"https://www.jax.org/strain/search?query=C19ORF25"},"sequence":{"accession":"Q9UFG5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UFG5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UFG5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UFG5"}},"corpus_meta":[{"pmid":"39657680","id":"PMC_39657680","title":"Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.","date":"2024","source":"Cell systems","url":"https://pubmed.ncbi.nlm.nih.gov/39657680","citation_count":4,"is_preprint":false},{"pmid":"41043659","id":"PMC_41043659","title":"The significance of urine extracellular vesicle DNA methylation detection in the diagnosis and classification of prostate cancer.","date":"2025","source":"Journal of advanced research","url":"https://pubmed.ncbi.nlm.nih.gov/41043659","citation_count":3,"is_preprint":false},{"pmid":"40527220","id":"PMC_40527220","title":"Characterization of methylation profile in biofluid cell-free DNA and identification of differentially methylated genes for phenotypic representations in Parkinson's disease.","date":"2025","source":"Clinical neurology and neurosurgery","url":"https://pubmed.ncbi.nlm.nih.gov/40527220","citation_count":1,"is_preprint":false},{"pmid":"38645119","id":"PMC_38645119","title":"Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38645119","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4450,"output_tokens":381,"usd":0.009532,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6606,"output_tokens":860,"usd":0.027265,"stage2_stop_reason":"end_turn"},"total_usd":0.036797,"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\": 2024,\n      \"finding\": \"Loss of C19orf25 enhances STING signaling; C19orf25 clustered with USE1 (a Golgi-to-ER transport protein) in a genome-wide optical pooled screen based on subcellular STING localization phenotypes, placing C19orf25 in a pathway involved in Golgi-to-ER retrograde transport that normally restrains STING signaling.\",\n      \"method\": \"Genome-wide optical pooled CRISPR screen with high-content subcellular imaging of STING localization in 45 million cells; phenotypic clustering; functional validation by measuring STING signaling upon gene loss\",\n      \"journal\": \"Cell systems\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen with imaging-based phenotyping and functional signaling readout, replicated in both preprint and peer-reviewed publication from same lab; no in vitro reconstitution or direct binding assay\",\n      \"pmids\": [\"39657680\", \"38645119\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"C19orf25 is a gene of previously unknown function that co-clusters with USE1 (a Golgi-to-ER retrograde transport factor) and whose loss enhances STING innate immune signaling, suggesting it plays a role in Golgi-to-ER transport that normally limits STING activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"C19orf25 is a functionally uncharacterized gene implicated in restraining STING-dependent innate immune signaling through a role in Golgi-to-ER retrograde transport [#0]. In a genome-wide optical pooled CRISPR screen scoring subcellular STING localization, loss of C19orf25 enhanced STING signaling, and C19orf25 co-clustered phenotypically with USE1, a Golgi-to-ER retrograde transport factor, placing it in a transport pathway that normally limits STING activity [#0]. Beyond this genetic and phenotypic association [#0], no direct molecular activity, binding partner, or biochemical mechanism for C19orf25 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether C19orf25 has any defined cellular role was unknown; a genome-wide imaging screen showed its loss enhances STING signaling and that it clusters with the retrograde transport factor USE1, establishing a candidate function in Golgi-to-ER transport that restrains STING.\",\n      \"evidence\": \"Genome-wide optical pooled CRISPR screen with high-content subcellular imaging of STING localization in 45 million cells, phenotypic clustering, and functional validation of STING signaling upon gene loss\",\n      \"pmids\": [\"39657680\", \"38645119\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct physical interaction between C19orf25 and USE1 or other transport machinery demonstrated\",\n        \"No in vitro reconstitution or biochemical assay defining a molecular activity\",\n        \"Mechanism by which the implicated transport pathway restrains STING not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity, direct binding partners, and subcellular localization of C19orf25, and the precise mechanism linking it to Golgi-to-ER transport and STING regulation, remain undefined.\",\n      \"evidence\": \"No further experimental characterization present in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or biochemical characterization\",\n        \"No confirmed localization data\",\n        \"No reciprocal validation of the USE1 association\"\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":2,"faith_total":2,"faith_pct":100.0}}