{"gene":"ZNF618","run_date":"2026-06-11T09:02:07","timeline":{"discoveries":[{"year":2016,"finding":"ZNF618 physically interacts with UHRF2 (but not its paralog UHRF1) and co-localizes with UHRF2 at genomic loci enriched for 5-hydroxymethylcytosine (5hmC). ZNF618 chromatin localization is mediated through its first two zinc fingers and is independent of its interaction with UHRF2, whereas ZNF618 regulates UHRF2 chromatin localization, thereby controlling UHRF2 function as a specific 5hmC reader in vivo.","method":"Co-immunoprecipitation, chromatin localization assays, domain-deletion/mutagenesis of zinc fingers, ChIP-based co-localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction specificity shown (UHRF2 but not UHRF1), domain mapping of zinc fingers, chromatin localization validated; single lab, multiple orthogonal methods reported in one study","pmids":["27129234"],"is_preprint":false}],"current_model":"ZNF618 is a chromatin-associated zinc finger protein whose first two zinc fingers mediate its recruitment to 5-hydroxymethylcytosine-enriched genomic loci, where it specifically binds UHRF2 (but not UHRF1) and regulates UHRF2 chromatin localization to enable its function as a 5hmC reader in vivo."},"narrative":{"mechanistic_narrative":"ZNF618 is a chromatin-associated zinc finger protein that functions as a regulator of UHRF2-dependent 5-hydroxymethylcytosine (5hmC) reading [PMID:27129234]. ZNF618 is recruited to 5hmC-enriched genomic loci through its first two zinc fingers, in a manner independent of its protein partners, and physically and selectively associates with UHRF2 but not its paralog UHRF1 [PMID:27129234]. By controlling the chromatin localization of UHRF2, ZNF618 enables UHRF2 to function as a specific 5hmC reader in vivo [PMID:27129234]. Beyond this interaction and its role in directing UHRF2 to chromatin, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Established that ZNF618 is a chromatin-targeting factor that confers UHRF2 its localization at 5hmC-rich loci, resolving how UHRF2 acts as a specific 5hmC reader in cells.","evidence":"Co-immunoprecipitation showing selective ZNF618-UHRF2 (not UHRF1) interaction, zinc-finger domain-deletion mapping of chromatin targeting, and ChIP-based co-localization at 5hmC loci in cells","pmids":["27129234"],"confidence":"Medium","gaps":["Single-lab study without independent replication of the interaction specificity","No structural model of the ZNF618 zinc fingers engaging chromatin or 5hmC","Downstream functional/transcriptional consequences of UHRF2 mislocalization upon ZNF618 loss not defined"]},{"year":null,"claim":"Whether ZNF618 directly recognizes 5hmC or is targeted by another chromatin feature, and the biological pathways downstream of the ZNF618-UHRF2 axis, remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Direct DNA/5hmC-binding specificity of the ZNF618 zinc fingers not biochemically defined","Physiological and developmental roles of ZNF618 uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":["UHRF2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5T7W0","full_name":"Zinc finger protein 618","aliases":[],"length_aa":954,"mass_kda":105.0,"function":"Regulates UHRF2 function as a specific 5-hydroxymethylcytosine (5hmC) reader by regulating its chromatin localization","subcellular_location":"Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/Q5T7W0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ZNF618","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ZNF618","total_profiled":1310},"omim":[{"mim_id":"617077","title":"ZINC FINGER PROTEIN 618; ZNF618","url":"https://www.omim.org/entry/617077"},{"mim_id":"615211","title":"UBIQUITIN-LIKE PROTEIN CONTAINING PHD AND RING FINGER DOMAINS 2, E3 UBIQUITIN PROTEIN LIGASE; UHRF2","url":"https://www.omim.org/entry/615211"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ZNF618"},"hgnc":{"alias_symbol":["KIAA1952","NEDD10"],"prev_symbol":[]},"alphafold":{"accession":"Q5T7W0","domains":[{"cath_id":"-","chopping":"142-168","consensus_level":"high","plddt":76.293,"start":142,"end":168},{"cath_id":"3.30.420","chopping":"523-635_920-952","consensus_level":"medium","plddt":85.0658,"start":523,"end":952},{"cath_id":"-","chopping":"648-798","consensus_level":"medium","plddt":84.7746,"start":648,"end":798}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T7W0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T7W0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T7W0-F1-predicted_aligned_error_v6.png","plddt_mean":64.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ZNF618","jax_strain_url":"https://www.jax.org/strain/search?query=ZNF618"},"sequence":{"accession":"Q5T7W0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5T7W0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5T7W0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T7W0"}},"corpus_meta":[{"pmid":"7958843","id":"PMC_7958843","title":"Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.","date":"1994","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/7958843","citation_count":601,"is_preprint":false},{"pmid":"27129234","id":"PMC_27129234","title":"Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27129234","citation_count":17,"is_preprint":false},{"pmid":"35320709","id":"PMC_35320709","title":"The mTOR chromatin-bound interactome in prostate cancer.","date":"2022","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/35320709","citation_count":16,"is_preprint":false},{"pmid":"21480186","id":"PMC_21480186","title":"Systematic candidate gene investigations in the SPA2 locus (9q32) show an association between TNFSF8 and susceptibility to spondylarthritis.","date":"2011","source":"Arthritis and rheumatism","url":"https://pubmed.ncbi.nlm.nih.gov/21480186","citation_count":8,"is_preprint":false},{"pmid":"39287932","id":"PMC_39287932","title":"Identification of risk loci for postpartum depression in a genome-wide association study.","date":"2024","source":"Psychiatry and clinical neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/39287932","citation_count":8,"is_preprint":false},{"pmid":"25869180","id":"PMC_25869180","title":"Habitual dietary intake of β-carotene, vitamin C, folate, or vitamin E may interact with single nucleotide polymorphisms on brachial-ankle pulse wave velocity in healthy adults.","date":"2015","source":"European journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/25869180","citation_count":7,"is_preprint":false},{"pmid":"26387843","id":"PMC_26387843","title":"Gene and dietary calcium interaction effects on brachial-ankle pulse wave velocity.","date":"2015","source":"Clinical nutrition (Edinburgh, Scotland)","url":"https://pubmed.ncbi.nlm.nih.gov/26387843","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5951,"output_tokens":410,"usd":0.012002,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6661,"output_tokens":958,"usd":0.028628,"stage2_stop_reason":"end_turn"},"total_usd":0.04063,"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\": 2016,\n      \"finding\": \"ZNF618 physically interacts with UHRF2 (but not its paralog UHRF1) and co-localizes with UHRF2 at genomic loci enriched for 5-hydroxymethylcytosine (5hmC). ZNF618 chromatin localization is mediated through its first two zinc fingers and is independent of its interaction with UHRF2, whereas ZNF618 regulates UHRF2 chromatin localization, thereby controlling UHRF2 function as a specific 5hmC reader in vivo.\",\n      \"method\": \"Co-immunoprecipitation, chromatin localization assays, domain-deletion/mutagenesis of zinc fingers, ChIP-based co-localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction specificity shown (UHRF2 but not UHRF1), domain mapping of zinc fingers, chromatin localization validated; single lab, multiple orthogonal methods reported in one study\",\n      \"pmids\": [\"27129234\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ZNF618 is a chromatin-associated zinc finger protein whose first two zinc fingers mediate its recruitment to 5-hydroxymethylcytosine-enriched genomic loci, where it specifically binds UHRF2 (but not UHRF1) and regulates UHRF2 chromatin localization to enable its function as a 5hmC reader in vivo.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ZNF618 is a chromatin-associated zinc finger protein that functions as a regulator of UHRF2-dependent 5-hydroxymethylcytosine (5hmC) reading [#0]. ZNF618 is recruited to 5hmC-enriched genomic loci through its first two zinc fingers, in a manner independent of its protein partners, and physically and selectively associates with UHRF2 but not its paralog UHRF1 [#0]. By controlling the chromatin localization of UHRF2, ZNF618 enables UHRF2 to function as a specific 5hmC reader in vivo [#0]. Beyond this interaction and its role in directing UHRF2 to chromatin, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established that ZNF618 is a chromatin-targeting factor that confers UHRF2 its localization at 5hmC-rich loci, resolving how UHRF2 acts as a specific 5hmC reader in cells.\",\n      \"evidence\": \"Co-immunoprecipitation showing selective ZNF618-UHRF2 (not UHRF1) interaction, zinc-finger domain-deletion mapping of chromatin targeting, and ChIP-based co-localization at 5hmC loci in cells\",\n      \"pmids\": [\"27129234\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study without independent replication of the interaction specificity\",\n        \"No structural model of the ZNF618 zinc fingers engaging chromatin or 5hmC\",\n        \"Downstream functional/transcriptional consequences of UHRF2 mislocalization upon ZNF618 loss not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ZNF618 directly recognizes 5hmC or is targeted by another chromatin feature, and the biological pathways downstream of the ZNF618-UHRF2 axis, remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct DNA/5hmC-binding specificity of the ZNF618 zinc fingers not biochemically defined\",\n        \"Physiological and developmental roles of ZNF618 uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"UHRF2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}