{"gene":"TVP23B","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2023,"finding":"TVP23B is a trans-Golgi transmembrane protein that controls Paneth cell homeostasis and goblet cell glycosylation function; loss of TVP23B leads to decreased antimicrobial peptides and a more penetrable mucus layer, compromising intestinal barrier integrity.","method":"Forward genetic screen (ENU mutagenesis) identifying Tvp23b mutation conferring colitis susceptibility; loss-of-function characterization in vivo with defined cellular phenotypes (Paneth cell homeostasis, goblet cell function)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotypes and pathway placement, single lab, multiple orthogonal readouts (antimicrobial peptides, mucus penetrability, Golgi proteomics)","pmids":["37339972"],"is_preprint":false},{"year":2023,"finding":"TVP23B physically binds the Golgi protein YIPF6; both proteins are required for intestinal homeostasis, and their deficiency results in a common reduction of critical glycosylation enzymes in the Golgi proteome of colonocytes.","method":"Co-immunoprecipitation / binding interaction identified in the context of Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — binding partner identified with functional corroboration via Golgi proteomics, single lab","pmids":["37339972"],"is_preprint":false},{"year":2023,"finding":"TVP23B is necessary for formation of the sterile (bacteria-free) mucin layer of the intestine; its absence disturbs the in vivo balance between host and microbiota.","method":"In vivo loss-of-function (Tvp23b mutant mice) with assessment of mucin layer sterility and host-microbe balance","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with specific functional readout (mucin layer barrier), single lab","pmids":["37339972"],"is_preprint":false},{"year":2014,"finding":"RNAi-mediated knockdown of FAM18B (TVP23B) in human retinal microvascular endothelial cells (HRMECs) enhances cell migration and tube formation, and exacerbates hyperglycemia-induced decrease in cell viability; these effects are reversed by the NF-κB inhibitor PDTC, placing TVP23B upstream of NF-κB signaling in HRMECs.","method":"siRNA knockdown in primary HRMECs with migration assay, tube formation assay, viability assay, and pharmacological rescue with NF-κB inhibitor PDTC","journal":"Molecular vision","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with multiple cellular phenotype readouts and pharmacological epistasis (NF-κB inhibitor rescue), single lab","pmids":["25221423"],"is_preprint":false},{"year":2025,"finding":"In vivo macrophage-specific silencing of Tvp23b using lipidoid nanoparticles in mice with myocardial infarction significantly improved cardiac function and suppressed fibrosis, indicating a role for TVP23B in macrophage-driven pro-fibrotic signaling in ischemic cardiomyopathy.","method":"In vivo macrophage-specific siRNA knockdown via lipidoid nanoparticles in MI mouse model; cardiac function and fibrosis measured as phenotypic readouts","journal":"medRxiv : the preprint server for health sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, single lab, in vivo knockdown with phenotypic readout but no direct molecular mechanism established for TVP23B specifically","pmids":["40894159"],"is_preprint":true}],"current_model":"TVP23B is a trans-Golgi transmembrane protein that binds YIPF6 and maintains Golgi glycosylation enzyme content in intestinal epithelial cells, thereby supporting Paneth cell homeostasis, goblet cell mucin glycosylation, and formation of a sterile mucus barrier against microbiota; in endothelial cells its loss activates NF-κB signaling to promote migration and angiogenic tube formation, and in macrophages its silencing suppresses pro-fibrotic paracrine programs."},"narrative":{"mechanistic_narrative":"TVP23B is a trans-Golgi transmembrane protein that maintains the glycosylation capacity of the Golgi apparatus in intestinal epithelial cells, thereby supporting epithelial barrier function [PMID:37339972]. It physically binds the Golgi protein YIPF6, and loss of either protein causes a common depletion of glycosylation enzymes from the colonocyte Golgi proteome, linking TVP23B to the maintenance of Golgi enzyme content [PMID:37339972]. Through this activity TVP23B controls Paneth cell homeostasis and goblet cell glycosylation, such that its loss reduces antimicrobial peptides and produces a more penetrable mucus layer [PMID:37339972]; it is specifically required to form the sterile, bacteria-free inner mucin layer that maintains the host–microbiota balance in vivo [PMID:37339972]. Beyond the intestine, knockdown of TVP23B in retinal microvascular endothelial cells enhances migration and tube formation in an NF-κB-dependent manner, as these effects are reversed by the NF-κB inhibitor PDTC, placing TVP23B upstream of NF-κB signaling in these cells [PMID:25221423]. The molecular basis by which a Golgi glycosylation regulator restrains NF-κB activation has not been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established the first cellular phenotype for TVP23B (FAM18B), showing it constrains endothelial migration and angiogenic behavior via NF-κB.","evidence":"siRNA knockdown in primary human retinal microvascular endothelial cells with migration, tube-formation, and viability assays plus pharmacological rescue using the NF-κB inhibitor PDTC","pmids":["25221423"],"confidence":"Medium","gaps":["No molecular link drawn between the Golgi/transmembrane identity of TVP23B and NF-κB activation","Direct biochemical targets or signaling intermediates are not identified","Effect shown only in one endothelial cell type by knockdown without rescue by re-expression"]},{"year":2023,"claim":"Defined TVP23B as a trans-Golgi protein required for intestinal barrier function and placed it within a Golgi glycosylation pathway through its partner YIPF6.","evidence":"ENU forward genetic screen identifying a colitis-susceptibility Tvp23b mutation, in vivo loss-of-function characterization of Paneth and goblet cells, co-immunoprecipitation of YIPF6, and Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes","pmids":["37339972"],"confidence":"Medium","gaps":["Mechanism by which TVP23B/YIPF6 retains or recruits glycosylation enzymes in the Golgi is not resolved","The interaction rests on co-immunoprecipitation without reciprocal or structural validation","Whether the endothelial NF-κB role and the intestinal glycosylation role share a common molecular mechanism is unaddressed"]},{"year":2025,"claim":"Extended TVP23B function to macrophages, indicating it supports a pro-fibrotic paracrine program relevant to ischemic cardiomyopathy.","evidence":"In vivo macrophage-specific siRNA knockdown via lipidoid nanoparticles in a mouse myocardial infarction model, with cardiac function and fibrosis as phenotypic readouts (preprint)","pmids":["40894159"],"confidence":"Low","gaps":["Preprint; no direct molecular mechanism established for TVP23B in macrophages","Downstream pro-fibrotic mediators are not identified","Cell-type-specific knockdown phenotype not corroborated by genetic deletion or rescue"]},{"year":null,"claim":"How TVP23B mechanistically maintains Golgi glycosylation enzyme content and how this connects to NF-κB signaling and macrophage pro-fibrotic programs remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical mechanism linking TVP23B–YIPF6 binding to enzyme retention","No unifying model across intestinal, endothelial, and macrophage contexts","No structural information on TVP23B or its complex with YIPF6"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":["YIPF6"],"other_free_text":[]}},"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":"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":9,"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":"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":"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},{"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6707,"output_tokens":1268,"usd":0.019571,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7925,"output_tokens":1763,"usd":0.04185,"stage2_stop_reason":"end_turn"},"total_usd":0.061421,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","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; loss of TVP23B leads to decreased antimicrobial peptides and a more penetrable mucus layer, compromising intestinal barrier integrity.\",\n      \"method\": \"Forward genetic screen (ENU mutagenesis) identifying Tvp23b mutation conferring colitis susceptibility; loss-of-function characterization in vivo with defined cellular phenotypes (Paneth cell homeostasis, goblet cell function)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotypes and pathway placement, single lab, multiple orthogonal readouts (antimicrobial peptides, mucus penetrability, Golgi proteomics)\",\n      \"pmids\": [\"37339972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TVP23B physically binds the Golgi protein YIPF6; both proteins are required for intestinal homeostasis, and their deficiency results in a common reduction of critical glycosylation enzymes in the Golgi proteome of colonocytes.\",\n      \"method\": \"Co-immunoprecipitation / binding interaction identified in the context of Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — binding partner identified with functional corroboration via Golgi proteomics, single lab\",\n      \"pmids\": [\"37339972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TVP23B is necessary for formation of the sterile (bacteria-free) mucin layer of the intestine; its absence disturbs the in vivo balance between host and microbiota.\",\n      \"method\": \"In vivo loss-of-function (Tvp23b mutant mice) with assessment of mucin layer sterility and host-microbe balance\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with specific functional readout (mucin layer barrier), single lab\",\n      \"pmids\": [\"37339972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"RNAi-mediated knockdown of FAM18B (TVP23B) in human retinal microvascular endothelial cells (HRMECs) enhances cell migration and tube formation, and exacerbates hyperglycemia-induced decrease in cell viability; these effects are reversed by the NF-κB inhibitor PDTC, placing TVP23B upstream of NF-κB signaling in HRMECs.\",\n      \"method\": \"siRNA knockdown in primary HRMECs with migration assay, tube formation assay, viability assay, and pharmacological rescue with NF-κB inhibitor PDTC\",\n      \"journal\": \"Molecular vision\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with multiple cellular phenotype readouts and pharmacological epistasis (NF-κB inhibitor rescue), single lab\",\n      \"pmids\": [\"25221423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In vivo macrophage-specific silencing of Tvp23b using lipidoid nanoparticles in mice with myocardial infarction significantly improved cardiac function and suppressed fibrosis, indicating a role for TVP23B in macrophage-driven pro-fibrotic signaling in ischemic cardiomyopathy.\",\n      \"method\": \"In vivo macrophage-specific siRNA knockdown via lipidoid nanoparticles in MI mouse model; cardiac function and fibrosis measured as phenotypic readouts\",\n      \"journal\": \"medRxiv : the preprint server for health sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, single lab, in vivo knockdown with phenotypic readout but no direct molecular mechanism established for TVP23B specifically\",\n      \"pmids\": [\"40894159\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"TVP23B is a trans-Golgi transmembrane protein that binds YIPF6 and maintains Golgi glycosylation enzyme content in intestinal epithelial cells, thereby supporting Paneth cell homeostasis, goblet cell mucin glycosylation, and formation of a sterile mucus barrier against microbiota; in endothelial cells its loss activates NF-κB signaling to promote migration and angiogenic tube formation, and in macrophages its silencing suppresses pro-fibrotic paracrine programs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TVP23B is a trans-Golgi transmembrane protein that maintains the glycosylation capacity of the Golgi apparatus in intestinal epithelial cells, thereby supporting epithelial barrier function [#0]. It physically binds the Golgi protein YIPF6, and loss of either protein causes a common depletion of glycosylation enzymes from the colonocyte Golgi proteome, linking TVP23B to the maintenance of Golgi enzyme content [#1]. Through this activity TVP23B controls Paneth cell homeostasis and goblet cell glycosylation, such that its loss reduces antimicrobial peptides and produces a more penetrable mucus layer [#0]; it is specifically required to form the sterile, bacteria-free inner mucin layer that maintains the host–microbiota balance in vivo [#2]. Beyond the intestine, knockdown of TVP23B in retinal microvascular endothelial cells enhances migration and tube formation in an NF-κB-dependent manner, as these effects are reversed by the NF-κB inhibitor PDTC, placing TVP23B upstream of NF-κB signaling in these cells [#3]. The molecular basis by which a Golgi glycosylation regulator restrains NF-κB activation has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established the first cellular phenotype for TVP23B (FAM18B), showing it constrains endothelial migration and angiogenic behavior via NF-κB.\",\n      \"evidence\": \"siRNA knockdown in primary human retinal microvascular endothelial cells with migration, tube-formation, and viability assays plus pharmacological rescue using the NF-κB inhibitor PDTC\",\n      \"pmids\": [\"25221423\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular link drawn between the Golgi/transmembrane identity of TVP23B and NF-κB activation\",\n        \"Direct biochemical targets or signaling intermediates are not identified\",\n        \"Effect shown only in one endothelial cell type by knockdown without rescue by re-expression\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined TVP23B as a trans-Golgi protein required for intestinal barrier function and placed it within a Golgi glycosylation pathway through its partner YIPF6.\",\n      \"evidence\": \"ENU forward genetic screen identifying a colitis-susceptibility Tvp23b mutation, in vivo loss-of-function characterization of Paneth and goblet cells, co-immunoprecipitation of YIPF6, and Golgi proteomics of TVP23B- and YIPF6-deficient colonocytes\",\n      \"pmids\": [\"37339972\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which TVP23B/YIPF6 retains or recruits glycosylation enzymes in the Golgi is not resolved\",\n        \"The interaction rests on co-immunoprecipitation without reciprocal or structural validation\",\n        \"Whether the endothelial NF-κB role and the intestinal glycosylation role share a common molecular mechanism is unaddressed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended TVP23B function to macrophages, indicating it supports a pro-fibrotic paracrine program relevant to ischemic cardiomyopathy.\",\n      \"evidence\": \"In vivo macrophage-specific siRNA knockdown via lipidoid nanoparticles in a mouse myocardial infarction model, with cardiac function and fibrosis as phenotypic readouts (preprint)\",\n      \"pmids\": [\"40894159\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Preprint; no direct molecular mechanism established for TVP23B in macrophages\",\n        \"Downstream pro-fibrotic mediators are not identified\",\n        \"Cell-type-specific knockdown phenotype not corroborated by genetic deletion or rescue\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TVP23B mechanistically maintains Golgi glycosylation enzyme content and how this connects to NF-κB signaling and macrophage pro-fibrotic programs remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No biochemical mechanism linking TVP23B–YIPF6 binding to enzyme retention\",\n        \"No unifying model across intestinal, endothelial, and macrophage contexts\",\n        \"No structural information on TVP23B or its complex with YIPF6\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"YIPF6\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}