{"gene":"TVP23B","run_date":"2026-04-28T21:43:00","timeline":{"discoveries":[{"year":2023,"finding":"TVP23B is a trans-Golgi transmembrane protein that controls Paneth cell homeostasis and goblet cell glycosylation function, leading to decreased antimicrobial peptides and a more penetrable mucus layer when absent; it physically binds the Golgi protein YIPF6, and both proteins are required for maintaining critical glycosylation enzymes in the Golgi proteome of colonocytes.","method":"Forward genetic screen (ENU mutagenesis), co-immunoprecipitation/binding assay (TVP23B–YIPF6 interaction), Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes, in vivo loss-of-function with chemically induced and infectious colitis phenotypic readouts","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (genetic screen, protein interaction, proteomics, in vivo phenotype) in a single rigorous study","pmids":["37339972"],"is_preprint":false},{"year":2023,"finding":"TVP23B is necessary for formation of the sterile mucin layer of the intestine; its absence disturbs the balance of host and microbe in vivo, demonstrating a direct role in intestinal barrier function.","method":"In vivo loss-of-function mouse model with mucus penetrability assays and microbiome analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — clean in vivo KO with defined cellular and mucosal phenotype, multiple readouts","pmids":["37339972"],"is_preprint":false},{"year":2025,"finding":"Macrophage-specific in vivo silencing of Tvp23b in mice with myocardial infarction significantly improved cardiac function and suppressed fibrosis, placing TVP23B in a macrophage niche-mediated fibroblast activation pathway.","method":"In vivo gene silencing via lipidoid nanoparticles targeting macrophages in MI mouse model, with cardiac function and fibrosis readouts; supported by spatial transcriptomics and in vitro macrophage secretome experiments","journal":"medRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — in vivo silencing with defined functional readout, but preprint and pathway placement partly computational","pmids":["40894159"],"is_preprint":true}],"current_model":"TVP23B is a conserved trans-Golgi transmembrane protein that physically interacts with YIPF6 to maintain Golgi glycosylation enzyme composition, thereby supporting Paneth cell homeostasis, goblet cell mucin glycosylation, and intestinal barrier integrity; additionally, in macrophages it participates in a niche-mediated signaling pathway that promotes cardiac fibroblast activation after myocardial infarction."},"narrative":{"teleology":[{"year":2023,"claim":"Forward genetics and proteomics established that TVP23B is a trans-Golgi protein that partners with YIPF6 to maintain Golgi glycosylation enzyme composition, thereby controlling Paneth cell function, goblet cell mucin glycosylation, and intestinal barrier integrity — answering how this previously uncharacterized transmembrane protein contributes to mucosal defense.","evidence":"ENU mutagenesis screen in mice, co-immunoprecipitation of TVP23B–YIPF6, Golgi proteomics of TVP23B/YIPF6-deficient colonocytes, in vivo mucus penetrability assays, and chemically/infectiously induced colitis models","pmids":["37339972"],"confidence":"High","gaps":["The mechanism by which TVP23B–YIPF6 interaction retains or recruits specific glycosylation enzymes to the Golgi is undefined","Whether TVP23B has direct enzymatic or transporter activity versus acting as a structural scaffold is unknown","Relevance of TVP23B-dependent glycosylation outside the intestinal epithelium has not been explored"]},{"year":2025,"claim":"Macrophage-specific silencing of Tvp23b after myocardial infarction improved cardiac function and reduced fibrosis, broadening TVP23B's biological role beyond intestinal epithelium to macrophage-mediated tissue remodeling.","evidence":"In vivo lipidoid nanoparticle-mediated silencing in macrophages in a mouse MI model, with spatial transcriptomics and macrophage secretome analysis (preprint)","pmids":["40894159"],"confidence":"Medium","gaps":["Preprint; awaits peer review and independent replication","The molecular mechanism linking TVP23B to macrophage secretory programs that activate cardiac fibroblasts is not defined","Whether the cardiac fibrosis role depends on the same Golgi glycosylation pathway described in colonocytes is untested"]},{"year":null,"claim":"The direct molecular activity of TVP23B — whether it acts as a cargo receptor, structural scaffold, or has intrinsic enzymatic function — remains unknown, as does the structural basis of its interaction with YIPF6.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of TVP23B or the TVP23B–YIPF6 complex exists","No substrate or direct enzymatic activity has been assigned to TVP23B","Tissue-specific and cell-type-specific functions beyond intestinal epithelium and macrophages are uncharacterized"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":[],"partners":["YIPF6"],"other_free_text":[]},"mechanistic_narrative":"TVP23B is a trans-Golgi transmembrane protein that physically interacts with YIPF6 and is required for maintaining critical glycosylation enzymes within the Golgi proteome of colonocytes, thereby controlling Paneth cell homeostasis, goblet cell mucin glycosylation, and the formation of a sterile intestinal mucus barrier [PMID:37339972]. Loss of TVP23B leads to decreased antimicrobial peptide production, a more penetrable mucus layer, and susceptibility to colitis [PMID:37339972]."},"prefetch_data":{"uniprot":{"accession":"Q9NYZ1","full_name":"Golgi apparatus membrane protein TVP23 homolog B","aliases":[],"length_aa":205,"mass_kda":23.6,"function":"","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q9NYZ1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TVP23B","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":5,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TVP23B","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Golgi apparatus","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TVP23B"},"hgnc":{"alias_symbol":["CGI-148","YDR084C"],"prev_symbol":["FAM18B","FAM18B1"]},"alphafold":{"accession":"Q9NYZ1","domains":[{"cath_id":"-","chopping":"35-191","consensus_level":"high","plddt":87.9798,"start":35,"end":191}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NYZ1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NYZ1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NYZ1-F1-predicted_aligned_error_v6.png","plddt_mean":80.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TVP23B","jax_strain_url":"https://www.jax.org/strain/search?query=TVP23B"},"sequence":{"accession":"Q9NYZ1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NYZ1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NYZ1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NYZ1"}},"corpus_meta":[{"pmid":"11381029","id":"PMC_11381029","title":"The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes.","date":"2001","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/11381029","citation_count":116,"is_preprint":false},{"pmid":"37339972","id":"PMC_37339972","title":"Trans-Golgi protein TVP23B regulates host-microbe interactions via Paneth cell homeostasis and Goblet cell glycosylation.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37339972","citation_count":12,"is_preprint":false},{"pmid":"25221423","id":"PMC_25221423","title":"Role of FAM18B in diabetic retinopathy.","date":"2014","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/25221423","citation_count":8,"is_preprint":false},{"pmid":"35565522","id":"PMC_35565522","title":"Identification of Candidate Genes for Pigmentation in Camels Using Genotyping-by-Sequencing.","date":"2022","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/35565522","citation_count":8,"is_preprint":false},{"pmid":"40894159","id":"PMC_40894159","title":"Interpretable machine learning coupled to spatial transcriptomics unveils mechanisms of macrophage-driven fibroblast activation in ischemic cardiomyopathy.","date":"2025","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40894159","citation_count":0,"is_preprint":false},{"pmid":"41616909","id":"PMC_41616909","title":"Transcriptomic integration nominates FOXN2 as a candidate schizophrenia risk gene.","date":"2026","source":"Behavioural brain research","url":"https://pubmed.ncbi.nlm.nih.gov/41616909","citation_count":0,"is_preprint":false},{"pmid":"41013918","id":"PMC_41013918","title":"Sequencing Analysis Demonstrates That a Complex Genetic Architecture Contributes to Risk for Spina Bifida.","date":"2025","source":"Birth defects research","url":"https://pubmed.ncbi.nlm.nih.gov/41013918","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5938,"output_tokens":798,"usd":0.014892},"stage2":{"model":"claude-opus-4-6","input_tokens":3982,"output_tokens":992,"usd":0.067065},"total_usd":0.081957,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"TVP23B is a trans-Golgi transmembrane protein that controls Paneth cell homeostasis and goblet cell glycosylation function, leading to decreased antimicrobial peptides and a more penetrable mucus layer when absent; it physically binds the Golgi protein YIPF6, and both proteins are required for maintaining critical glycosylation enzymes in the Golgi proteome of colonocytes.\",\n      \"method\": \"Forward genetic screen (ENU mutagenesis), co-immunoprecipitation/binding assay (TVP23B–YIPF6 interaction), Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes, in vivo loss-of-function with chemically induced and infectious colitis phenotypic readouts\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (genetic screen, protein interaction, proteomics, in vivo phenotype) in a single rigorous study\",\n      \"pmids\": [\"37339972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TVP23B is necessary for formation of the sterile mucin layer of the intestine; its absence disturbs the balance of host and microbe in vivo, demonstrating a direct role in intestinal barrier function.\",\n      \"method\": \"In vivo loss-of-function mouse model with mucus penetrability assays and microbiome analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean in vivo KO with defined cellular and mucosal phenotype, multiple readouts\",\n      \"pmids\": [\"37339972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Macrophage-specific in vivo silencing of Tvp23b in mice with myocardial infarction significantly improved cardiac function and suppressed fibrosis, placing TVP23B in a macrophage niche-mediated fibroblast activation pathway.\",\n      \"method\": \"In vivo gene silencing via lipidoid nanoparticles targeting macrophages in MI mouse model, with cardiac function and fibrosis readouts; supported by spatial transcriptomics and in vitro macrophage secretome experiments\",\n      \"journal\": \"medRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — in vivo silencing with defined functional readout, but preprint and pathway placement partly computational\",\n      \"pmids\": [\"40894159\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"TVP23B is a conserved trans-Golgi transmembrane protein that physically interacts with YIPF6 to maintain Golgi glycosylation enzyme composition, thereby supporting Paneth cell homeostasis, goblet cell mucin glycosylation, and intestinal barrier integrity; additionally, in macrophages it participates in a niche-mediated signaling pathway that promotes cardiac fibroblast activation after myocardial infarction.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TVP23B is a trans-Golgi transmembrane protein that physically interacts with YIPF6 and is required for maintaining critical glycosylation enzymes within the Golgi proteome of colonocytes, thereby controlling Paneth cell homeostasis, goblet cell mucin glycosylation, and the formation of a sterile intestinal mucus barrier [PMID:37339972]. Loss of TVP23B leads to decreased antimicrobial peptide production, a more penetrable mucus layer, and susceptibility to colitis [PMID:37339972].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Forward genetics and proteomics established that TVP23B is a trans-Golgi protein that partners with YIPF6 to maintain Golgi glycosylation enzyme composition, thereby controlling Paneth cell function, goblet cell mucin glycosylation, and intestinal barrier integrity — answering how this previously uncharacterized transmembrane protein contributes to mucosal defense.\",\n      \"evidence\": \"ENU mutagenesis screen in mice, co-immunoprecipitation of TVP23B–YIPF6, Golgi proteomics of TVP23B/YIPF6-deficient colonocytes, in vivo mucus penetrability assays, and chemically/infectiously induced colitis models\",\n      \"pmids\": [\"37339972\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The mechanism by which TVP23B–YIPF6 interaction retains or recruits specific glycosylation enzymes to the Golgi is undefined\",\n        \"Whether TVP23B has direct enzymatic or transporter activity versus acting as a structural scaffold is unknown\",\n        \"Relevance of TVP23B-dependent glycosylation outside the intestinal epithelium has not been explored\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Macrophage-specific silencing of Tvp23b after myocardial infarction improved cardiac function and reduced fibrosis, broadening TVP23B's biological role beyond intestinal epithelium to macrophage-mediated tissue remodeling.\",\n      \"evidence\": \"In vivo lipidoid nanoparticle-mediated silencing in macrophages in a mouse MI model, with spatial transcriptomics and macrophage secretome analysis (preprint)\",\n      \"pmids\": [\"40894159\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint; awaits peer review and independent replication\",\n        \"The molecular mechanism linking TVP23B to macrophage secretory programs that activate cardiac fibroblasts is not defined\",\n        \"Whether the cardiac fibrosis role depends on the same Golgi glycosylation pathway described in colonocytes is untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular activity of TVP23B — whether it acts as a cargo receptor, structural scaffold, or has intrinsic enzymatic function — remains unknown, as does the structural basis of its interaction with YIPF6.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of TVP23B or the TVP23B–YIPF6 complex exists\",\n        \"No substrate or direct enzymatic activity has been assigned to TVP23B\",\n        \"Tissue-specific and cell-type-specific functions beyond intestinal epithelium and macrophages are uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"YIPF6\"],\n    \"other_free_text\": []\n  }\n}\n```"}