{"gene":"FAM174C","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2006,"finding":"C19orf24 (FAM174C) encodes a non-classical secreted protein that lacks a signal peptide but is secreted extracellularly via a pathway independent of the classical ER-Golgi route, as demonstrated by its resistance to the secretion inhibitor brefeldin A (BFA) and its failure to co-localize with the Golgi apparatus in HeLa cells.","method":"Subcellular localization by live-cell fluorescence imaging (co-transfection with pEYFP-Golgi), brefeldin A inhibition assay, and deglycosylation analysis with PNGase F","journal":"Cellular & molecular biology letters","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple orthogonal methods (BFA inhibition, co-localization imaging, PNGase F deglycosylation) in a single lab establishing non-classical secretion and Golgi-independent trafficking","pmids":["16847563"],"is_preprint":false},{"year":2006,"finding":"C19orf24 (FAM174C) has no N-glycosylation modification sites, as confirmed by PNGase F deglycosylation analysis, and its tissue expression is restricted to the human liver with preferential expression in normal versus tumor tissue, as determined by RT-PCR.","method":"Deglycosylation assay with PNGase F; reverse transcription-PCR across multiple tissues","journal":"Cellular & molecular biology letters","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — direct biochemical assay (PNGase F) and RT-PCR, single lab, two orthogonal methods for two distinct findings","pmids":["16847563"],"is_preprint":false}],"current_model":"FAM174C (C19orf24) encodes a recently evolved, liver-expressed non-classical secreted protein that lacks a signal peptide and N-glycosylation, and is secreted via a brefeldin A-insensitive, Golgi-independent pathway whose molecular identity remains unknown."},"narrative":{"mechanistic_narrative":"FAM174C (C19orf24) encodes a non-classically secreted protein that reaches the extracellular space independently of the canonical ER-Golgi route: it lacks a signal peptide, its secretion is resistant to brefeldin A, and it fails to co-localize with the Golgi apparatus [PMID:16847563]. The protein carries no N-glycosylation, and its expression is restricted to liver with preferential expression in normal over tumor tissue [PMID:16847563]. Beyond these observations of unconventional secretion and tissue-restricted expression, no molecular activity, binding partner, or downstream pathway for FAM174C has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Whether FAM174C, a protein lacking a signal peptide, is retained intracellularly or exported was unknown; defining its trafficking route established it as a non-classically secreted protein bypassing the ER-Golgi pathway.","evidence":"Live-cell fluorescence imaging with a Golgi marker, brefeldin A inhibition assay, and PNGase F deglycosylation in HeLa cells","pmids":["16847563"],"confidence":"Medium","gaps":["The molecular identity of the Golgi-independent secretion pathway is unknown","No secretion machinery or chaperone partner identified","Trafficking demonstrated in HeLa cells, not in the native liver context"]},{"year":2006,"claim":"The post-translational modification status and tissue distribution were uncharacterized; showing absence of N-glycosylation and liver-restricted expression localized the protein's biological context.","evidence":"PNGase F deglycosylation assay and RT-PCR across multiple human tissues","pmids":["16847563"],"confidence":"Medium","gaps":["Functional consequence of preferential normal-versus-tumor expression unknown","No protein-level confirmation of tissue distribution","Other potential post-translational modifications not assessed"]},{"year":null,"claim":"The molecular function, binding partners, and the identity of the unconventional secretion pathway used by FAM174C remain unknown.","evidence":"No further mechanistic studies in the available corpus","pmids":[],"confidence":"Medium","gaps":["No molecular activity assigned","No physical interaction partners identified","The non-classical secretion route remains molecularly undefined"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005576","term_label":"extracellular region","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BVV8","full_name":"Protein FAM174C","aliases":[],"length_aa":132,"mass_kda":14.2,"function":"","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q9BVV8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FAM174C","classification":"Not Classified","n_dependent_lines":31,"n_total_lines":1208,"dependency_fraction":0.02566225165562914},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000228300","cell_line_id":"CID000378","localizations":[{"compartment":"golgi","grade":3},{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"MAP2K7","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000378","total_profiled":1310},"omim":[{"mim_id":"621536","title":"FAMILY WITH SEQUENCE SIMILARITY 174, MEMBER C; FAM174C","url":"https://www.omim.org/entry/621536"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear speckles","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FAM174C"},"hgnc":{"alias_symbol":["FLJ20640"],"prev_symbol":["C19orf24"]},"alphafold":{"accession":"Q9BVV8","domains":[{"cath_id":"-","chopping":"9-17_80-96","consensus_level":"medium","plddt":76.83,"start":9,"end":96}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVV8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVV8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVV8-F1-predicted_aligned_error_v6.png","plddt_mean":63.72},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FAM174C","jax_strain_url":"https://www.jax.org/strain/search?query=FAM174C"},"sequence":{"accession":"Q9BVV8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BVV8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BVV8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVV8"}},"corpus_meta":[{"pmid":"31893575","id":"PMC_31893575","title":"FOLFOX treatment response prediction in metastatic or recurrent colorectal cancer patients via machine learning algorithms.","date":"2020","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31893575","citation_count":32,"is_preprint":false},{"pmid":"20623358","id":"PMC_20623358","title":"Breakpoint determination of 15 large deletions in Peutz-Jeghers subjects.","date":"2010","source":"Human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20623358","citation_count":23,"is_preprint":false},{"pmid":"16847563","id":"PMC_16847563","title":"A novel recently evolved gene C19orf24 encodes a non-classical secreted protein.","date":"2006","source":"Cellular & molecular biology letters","url":"https://pubmed.ncbi.nlm.nih.gov/16847563","citation_count":6,"is_preprint":false},{"pmid":"40877397","id":"PMC_40877397","title":"Integrated analysis of m6A regulator mediated RNA methylation and key immune related genes in ischemic stroke.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/40877397","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4554,"output_tokens":585,"usd":0.011218,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6910,"output_tokens":1012,"usd":0.029925,"stage2_stop_reason":"end_turn"},"total_usd":0.041143,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"C19orf24 (FAM174C) encodes a non-classical secreted protein that lacks a signal peptide but is secreted extracellularly via a pathway independent of the classical ER-Golgi route, as demonstrated by its resistance to the secretion inhibitor brefeldin A (BFA) and its failure to co-localize with the Golgi apparatus in HeLa cells.\",\n      \"method\": \"Subcellular localization by live-cell fluorescence imaging (co-transfection with pEYFP-Golgi), brefeldin A inhibition assay, and deglycosylation analysis with PNGase F\",\n      \"journal\": \"Cellular & molecular biology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple orthogonal methods (BFA inhibition, co-localization imaging, PNGase F deglycosylation) in a single lab establishing non-classical secretion and Golgi-independent trafficking\",\n      \"pmids\": [\"16847563\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"C19orf24 (FAM174C) has no N-glycosylation modification sites, as confirmed by PNGase F deglycosylation analysis, and its tissue expression is restricted to the human liver with preferential expression in normal versus tumor tissue, as determined by RT-PCR.\",\n      \"method\": \"Deglycosylation assay with PNGase F; reverse transcription-PCR across multiple tissues\",\n      \"journal\": \"Cellular & molecular biology letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — direct biochemical assay (PNGase F) and RT-PCR, single lab, two orthogonal methods for two distinct findings\",\n      \"pmids\": [\"16847563\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FAM174C (C19orf24) encodes a recently evolved, liver-expressed non-classical secreted protein that lacks a signal peptide and N-glycosylation, and is secreted via a brefeldin A-insensitive, Golgi-independent pathway whose molecular identity remains unknown.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FAM174C (C19orf24) encodes a non-classically secreted protein that reaches the extracellular space independently of the canonical ER-Golgi route: it lacks a signal peptide, its secretion is resistant to brefeldin A, and it fails to co-localize with the Golgi apparatus [#0]. The protein carries no N-glycosylation, and its expression is restricted to liver with preferential expression in normal over tumor tissue [#1]. Beyond these observations of unconventional secretion and tissue-restricted expression, no molecular activity, binding partner, or downstream pathway for FAM174C has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Whether FAM174C, a protein lacking a signal peptide, is retained intracellularly or exported was unknown; defining its trafficking route established it as a non-classically secreted protein bypassing the ER-Golgi pathway.\",\n      \"evidence\": \"Live-cell fluorescence imaging with a Golgi marker, brefeldin A inhibition assay, and PNGase F deglycosylation in HeLa cells\",\n      \"pmids\": [\"16847563\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular identity of the Golgi-independent secretion pathway is unknown\",\n        \"No secretion machinery or chaperone partner identified\",\n        \"Trafficking demonstrated in HeLa cells, not in the native liver context\"\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"The post-translational modification status and tissue distribution were uncharacterized; showing absence of N-glycosylation and liver-restricted expression localized the protein's biological context.\",\n      \"evidence\": \"PNGase F deglycosylation assay and RT-PCR across multiple human tissues\",\n      \"pmids\": [\"16847563\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of preferential normal-versus-tumor expression unknown\",\n        \"No protein-level confirmation of tissue distribution\",\n        \"Other potential post-translational modifications not assessed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function, binding partners, and the identity of the unconventional secretion pathway used by FAM174C remain unknown.\",\n      \"evidence\": \"No further mechanistic studies in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular activity assigned\",\n        \"No physical interaction partners identified\",\n        \"The non-classical secretion route remains molecularly undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005576\", \"supporting_discovery_ids\": [0]}\n    ],\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}}