{"gene":"ZNF573","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2015,"finding":"Targeted delivery of ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation, indicating ZNF573 functions as a transcriptional repressor in the neuroendocrine control of puberty.","method":"Stereotaxic targeted delivery of ZNF573 construct to rat hypothalamus with assessment of pubertal timing as functional readout","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct in vivo gain-of-function with defined phenotypic readout (delayed puberty), but mechanistic detail for ZNF573 specifically (vs. GATAD1, which is more deeply characterized) is limited to the phenotype with no substrate identification for ZNF573 alone","pmids":["26671628"],"is_preprint":false},{"year":2025,"finding":"ZNF573 acts as a transcription factor that promotes expression of the E3 ubiquitin ligase RNF19B, which in turn regulates ubiquitination of PIK3CA; ZNF573 overexpression inhibits prostate cancer cell proliferation and invasion in vitro and in vivo.","method":"ZNF573 overexpression in prostate cancer cells (in vitro and in vivo xenograft), assessment of RNF19B expression, and PIK3CA ubiquitination assay","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional overexpression with defined pathway placement (ZNF573→RNF19B→PIK3CA ubiquitination), but single lab, single study, and abstract does not detail mutagenesis or reconstitution","pmids":["40973794"],"is_preprint":false}],"current_model":"ZNF573 is a transcription factor that represses transcriptional programs (including in the hypothalamus to restrain puberty onset) and, in prostate tissue, promotes expression of the E3 ubiquitin ligase RNF19B, thereby driving ubiquitination of PIK3CA and suppressing prostate cancer cell proliferation and invasion; its promoter is subject to aging-associated hypermethylation that silences these functions."},"narrative":{"mechanistic_narrative":"ZNF573 is a transcription factor that controls cell- and tissue-specific gene expression programs governing developmental timing and proliferation [PMID:26671628, PMID:40973794]. In the neuroendocrine control of puberty, delivery of ZNF573 to the rat hypothalamus delays pubertal onset by impairing the transition of a transcriptional network from a repressive epigenetic configuration toward activation, defining ZNF573 as a transcriptional repressor in this setting [PMID:26671628]. In prostate cancer cells, ZNF573 instead promotes expression of the E3 ubiquitin ligase RNF19B, which drives ubiquitination of PIK3CA, and ZNF573 overexpression suppresses proliferation and invasion both in vitro and in xenografts [PMID:40973794]. Beyond these two contexts, the direct DNA-binding targets, structural basis of transcriptional regulation, and mechanism by which ZNF573 selects activating versus repressive outputs have not been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Established that ZNF573 functions as a transcriptional repressor in vivo, linking it to the neuroendocrine timing of puberty rather than leaving it an uncharacterized zinc-finger protein.","evidence":"Stereotaxic targeted delivery of a ZNF573 construct to the rat hypothalamus with pubertal timing as functional readout","pmids":["26671628"],"confidence":"Medium","gaps":["No direct DNA-binding targets or response elements identified for ZNF573","Mechanism distinguishing ZNF573's contribution from co-studied factors not resolved","No structural or domain-level basis for repressive activity"]},{"year":2025,"claim":"Placed ZNF573 in a defined regulatory axis by showing it promotes RNF19B expression to drive PIK3CA ubiquitination and restrain prostate cancer cell proliferation and invasion.","evidence":"ZNF573 overexpression in prostate cancer cells (in vitro and xenograft) with RNF19B expression analysis and PIK3CA ubiquitination assay","pmids":["40973794"],"confidence":"Medium","gaps":["Single lab, single study without mutagenesis or reconstitution","Whether ZNF573 binds the RNF19B promoter directly is not established","Reconciliation of repressor (hypothalamus) versus activator (RNF19B) roles is unresolved"]},{"year":null,"claim":"How ZNF573 selects its genomic targets and switches between transcriptional activation and repression across tissues remains unknown.","evidence":"No direct genome-wide binding or structural data in the available corpus","pmids":[],"confidence":"Low","gaps":["No ChIP-seq or direct binding-site identification","No structural model of the DNA-binding domain","Cofactors mediating activating versus repressive outputs unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86YE8","full_name":"Zinc finger protein 573","aliases":[],"length_aa":665,"mass_kda":78.2,"function":"May be involved in transcriptional regulation","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q86YE8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF573","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ZNF573","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Intermediate filaments","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZNF573"},"hgnc":{"alias_symbol":["FLJ30921"],"prev_symbol":[]},"alphafold":{"accession":"Q86YE8","domains":[{"cath_id":"3.30.160.60","chopping":"268-407","consensus_level":"medium","plddt":79.6598,"start":268,"end":407},{"cath_id":"3.30.160.60","chopping":"611-664","consensus_level":"medium","plddt":84.6376,"start":611,"end":664},{"cath_id":"1.20.50","chopping":"31-86","consensus_level":"high","plddt":74.2009,"start":31,"end":86}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YE8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YE8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86YE8-F1-predicted_aligned_error_v6.png","plddt_mean":75.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF573","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF573"},"sequence":{"accession":"Q86YE8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86YE8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86YE8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86YE8"}},"corpus_meta":[{"pmid":"26671628","id":"PMC_26671628","title":"Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26671628","citation_count":71,"is_preprint":false},{"pmid":"30664178","id":"PMC_30664178","title":"Identification of key genes and pathways involved in microsatellite instability in colorectal cancer.","date":"2019","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/30664178","citation_count":27,"is_preprint":false},{"pmid":"30362566","id":"PMC_30362566","title":"The transcriptome profiles and methylation status revealed the potential cancer-related lncRNAs in patients with cervical cancer.","date":"2018","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30362566","citation_count":22,"is_preprint":false},{"pmid":"34995016","id":"PMC_34995016","title":"A combined biomarker panel shows improved sensitivity and specificity for detection of ovarian cancer.","date":"2022","source":"Journal of clinical laboratory analysis","url":"https://pubmed.ncbi.nlm.nih.gov/34995016","citation_count":7,"is_preprint":false},{"pmid":"36672361","id":"PMC_36672361","title":"Serum Mass Spectrometry Proteomics and Protein Set Identification in Response to FOLFOX-4 in Drug-Resistant Ovarian Carcinoma.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/36672361","citation_count":6,"is_preprint":false},{"pmid":"40973794","id":"PMC_40973794","title":"Aging-associated ZNF573 methylation regulates RNF19B-PIK3CA ubiquitination to promote prostate cancer.","date":"2025","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/40973794","citation_count":0,"is_preprint":false},{"pmid":"41952686","id":"PMC_41952686","title":"Novel transcriptomic alterations in poorly differentiated endometrial carcinomas: evidence from South African women.","date":"2026","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41952686","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6402,"output_tokens":628,"usd":0.014313,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6985,"output_tokens":1319,"usd":0.03395,"stage2_stop_reason":"end_turn"},"total_usd":0.048263,"stage1_batch_id":"msgbatch_01UT1AahFPCAyn2uVweS7A9z","stage2_batch_id":"msgbatch_01HuKWtKNT4Pqj1bc8eEP5RV","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"Targeted delivery of ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation, indicating ZNF573 functions as a transcriptional repressor in the neuroendocrine control of puberty.\",\n      \"method\": \"Stereotaxic targeted delivery of ZNF573 construct to rat hypothalamus with assessment of pubertal timing as functional readout\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct in vivo gain-of-function with defined phenotypic readout (delayed puberty), but mechanistic detail for ZNF573 specifically (vs. GATAD1, which is more deeply characterized) is limited to the phenotype with no substrate identification for ZNF573 alone\",\n      \"pmids\": [\"26671628\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ZNF573 acts as a transcription factor that promotes expression of the E3 ubiquitin ligase RNF19B, which in turn regulates ubiquitination of PIK3CA; ZNF573 overexpression inhibits prostate cancer cell proliferation and invasion in vitro and in vivo.\",\n      \"method\": \"ZNF573 overexpression in prostate cancer cells (in vitro and in vivo xenograft), assessment of RNF19B expression, and PIK3CA ubiquitination assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional overexpression with defined pathway placement (ZNF573→RNF19B→PIK3CA ubiquitination), but single lab, single study, and abstract does not detail mutagenesis or reconstitution\",\n      \"pmids\": [\"40973794\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF573 is a transcription factor that represses transcriptional programs (including in the hypothalamus to restrain puberty onset) and, in prostate tissue, promotes expression of the E3 ubiquitin ligase RNF19B, thereby driving ubiquitination of PIK3CA and suppressing prostate cancer cell proliferation and invasion; its promoter is subject to aging-associated hypermethylation that silences these functions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF573 is a transcription factor that controls cell- and tissue-specific gene expression programs governing developmental timing and proliferation [#0, #1]. In the neuroendocrine control of puberty, delivery of ZNF573 to the rat hypothalamus delays pubertal onset by impairing the transition of a transcriptional network from a repressive epigenetic configuration toward activation, defining ZNF573 as a transcriptional repressor in this setting [#0]. In prostate cancer cells, ZNF573 instead promotes expression of the E3 ubiquitin ligase RNF19B, which drives ubiquitination of PIK3CA, and ZNF573 overexpression suppresses proliferation and invasion both in vitro and in xenografts [#1]. Beyond these two contexts, the direct DNA-binding targets, structural basis of transcriptional regulation, and mechanism by which ZNF573 selects activating versus repressive outputs have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Established that ZNF573 functions as a transcriptional repressor in vivo, linking it to the neuroendocrine timing of puberty rather than leaving it an uncharacterized zinc-finger protein.\",\n      \"evidence\": \"Stereotaxic targeted delivery of a ZNF573 construct to the rat hypothalamus with pubertal timing as functional readout\",\n      \"pmids\": [\"26671628\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct DNA-binding targets or response elements identified for ZNF573\",\n        \"Mechanism distinguishing ZNF573's contribution from co-studied factors not resolved\",\n        \"No structural or domain-level basis for repressive activity\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placed ZNF573 in a defined regulatory axis by showing it promotes RNF19B expression to drive PIK3CA ubiquitination and restrain prostate cancer cell proliferation and invasion.\",\n      \"evidence\": \"ZNF573 overexpression in prostate cancer cells (in vitro and xenograft) with RNF19B expression analysis and PIK3CA ubiquitination assay\",\n      \"pmids\": [\"40973794\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study without mutagenesis or reconstitution\",\n        \"Whether ZNF573 binds the RNF19B promoter directly is not established\",\n        \"Reconciliation of repressor (hypothalamus) versus activator (RNF19B) roles is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ZNF573 selects its genomic targets and switches between transcriptional activation and repression across tissues remains unknown.\",\n      \"evidence\": \"No direct genome-wide binding or structural data in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No ChIP-seq or direct binding-site identification\",\n        \"No structural model of the DNA-binding domain\",\n        \"Cofactors mediating activating versus repressive outputs unidentified\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}