{"gene":"UNK","run_date":"2026-06-10T10:51:56","timeline":{"discoveries":[{"year":2025,"finding":"In C. elegans, UNK-1 (ortholog of mammalian Unkempt/UNK) is expressed cytoplasmically in head neurons, and its depletion via an auxin-inducible degron system results in increased head oscillations, a phenotype associated with defects in neurotransmitter synthesis, linking UNK-1 to head motor control.","method":"Genome editing (auxin-inducible degron tag + mNeonGreen knock-in), live imaging for subcellular localization, targeted protein depletion with behavioral phenotypic readout","journal":"microPublication biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with defined cellular/behavioral phenotype and direct localization, single study in C. elegans ortholog","pmids":["40575442"],"is_preprint":false},{"year":2024,"finding":"Mammalian Unkempt (UNK) protein localizes to centrosomes and Cep131-positive centriolar satellites, and is required for Plk4-induced centriole overduplication in an RNA-binding-dependent manner. UNK interacts with CNOT9, a component of the translational inhibitory CCR4-NOT complex, which also localizes to centrosomes during early centrosome amplification. Centriolar satellites and UNK promote local translation at centrosomes, and a transient downregulation of centrosomal translation occurs early in Plk4-induced centrosome amplification.","method":"Immunofluorescence/localization studies, co-immunoprecipitation (UNK–CNOT9 interaction), RNA-binding-dependent functional rescue, loss-of-function analysis of centriole overduplication, proximity-ligation or translation reporters at centrosomes","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (localization, Co-IP, RNA-binding-dependent rescue, translation reporters) in a single preprint study; not yet peer-reviewed","pmids":[],"is_preprint":true}],"current_model":"UNK (Unkempt) is a conserved cytoplasmic RNA-binding protein that localizes to centrosomes and centriolar satellites in mammalian cells, where it interacts with the CCR4-NOT complex component CNOT9 and promotes local translation required for Plk4-induced centriole overduplication; in C. elegans, its ortholog UNK-1 is expressed in head neurons and controls head motor behavior, consistent with a role in neuronal translational regulation."},"narrative":{"mechanistic_narrative":"UNK (Unkempt) is a conserved cytoplasmic RNA-binding protein implicated in localized translational control in both centrosomal and neuronal contexts [PMID:40575442]. In mammalian cells, UNK localizes to centrosomes and Cep131-positive centriolar satellites and is required, in an RNA-binding-dependent manner, for Plk4-induced centriole overduplication; it interacts with the CCR4-NOT component CNOT9 and, together with centriolar satellites, promotes local translation at centrosomes during early centrosome amplification. In C. elegans, the ortholog UNK-1 is expressed cytoplasmically in head neurons, and its depletion increases head oscillations, linking UNK to head motor control consistent with a role in neuronal translational regulation [PMID:40575442]. Beyond these contexts, the molecular targets of UNK-dependent translation and the structural basis of its RNA binding have not been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Established that mammalian UNK acts at the centrosome to support centriole biogenesis through RNA-binding-dependent local translation, identifying a physical link to the CCR4-NOT translational machinery.","evidence":"Immunofluorescence localization, UNK–CNOT9 co-immunoprecipitation, RNA-binding-dependent functional rescue, and translation reporters in mammalian cells (preprint)","pmids":[],"confidence":"Medium","gaps":["Specific mRNA targets translated locally at centrosomes are not identified","Mechanism by which UNK is recruited to centriolar satellites is unknown","Not yet peer-reviewed and CNOT9 interaction rests on a single Co-IP without reciprocal validation"]},{"year":2025,"claim":"Demonstrated an in vivo neuronal function for the UNK ortholog, showing that UNK-1 in head neurons controls head motor behavior, consistent with translational regulation in a whole-organism context.","evidence":"Auxin-inducible degron depletion with mNeonGreen knock-in, live imaging, and behavioral readout in C. elegans","pmids":["40575442"],"confidence":"Medium","gaps":["Molecular targets of UNK-1 in head neurons are not defined","Link between the behavioral phenotype and translational/RNA-binding activity is inferred, not demonstrated","Single study in the C. elegans ortholog"]},{"year":null,"claim":"Whether UNK's centrosomal and neuronal functions reflect a single conserved translational-control mechanism, and the identity of its regulated mRNAs, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct RNA targets identified in either context","No structural model of UNK RNA recognition","Conservation of the centrosomal role into the C. elegans system untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]}],"pathway":[],"complexes":[],"partners":["CNOT9"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9C0B0","full_name":"RING finger protein unkempt homolog","aliases":["Zinc finger CCCH domain-containing protein 5"],"length_aa":810,"mass_kda":88.1,"function":"Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9C0B0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/UNK","classification":"Not Classified","n_dependent_lines":15,"n_total_lines":1208,"dependency_fraction":0.012417218543046357},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/UNK","total_profiled":1310},"omim":[{"mim_id":"617463","title":"UNKEMPT FAMILY-LIKE ZINC FINGER; UNKL","url":"https://www.omim.org/entry/617463"},{"mim_id":"616375","title":"UNKEMPT FAMILY ZINC FINGER PROTEIN; UNK","url":"https://www.omim.org/entry/616375"},{"mim_id":"608048","title":"SNF2, LINKER HISTONE, PHD FINGER, RING FINGER, AND HELICASE DOMAINS-CONTAINING PROTEIN; SHPRH","url":"https://www.omim.org/entry/608048"},{"mim_id":"300773","title":"APEX NUCLEASE (APURINIC/APYRIMIDINIC ENDONUCLEASE) 2; APEX2","url":"https://www.omim.org/entry/300773"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Cytoplasmic bodies","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/UNK"},"hgnc":{"alias_symbol":["KIAA1753"],"prev_symbol":["ZC3HDC5","ZC3H5"]},"alphafold":{"accession":"Q9C0B0","domains":[{"cath_id":"-","chopping":"28-171","consensus_level":"medium","plddt":93.4676,"start":28,"end":171},{"cath_id":"-","chopping":"187-312","consensus_level":"high","plddt":89.4267,"start":187,"end":312},{"cath_id":"-","chopping":"768-801","consensus_level":"medium","plddt":84.0729,"start":768,"end":801},{"cath_id":"1.20.5","chopping":"667-714","consensus_level":"medium","plddt":93.5802,"start":667,"end":714}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0B0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0B0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9C0B0-F1-predicted_aligned_error_v6.png","plddt_mean":64.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=UNK","jax_strain_url":"https://www.jax.org/strain/search?query=UNK"},"sequence":{"accession":"Q9C0B0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9C0B0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9C0B0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9C0B0"}},"corpus_meta":[{"pmid":"20061017","id":"PMC_20061017","title":"Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua.","date":"2010","source":"Placenta","url":"https://pubmed.ncbi.nlm.nih.gov/20061017","citation_count":161,"is_preprint":false},{"pmid":"31331391","id":"PMC_31331391","title":"The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice.","date":"2019","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/31331391","citation_count":76,"is_preprint":false},{"pmid":"17362384","id":"PMC_17362384","title":"Possible roles of KIR2DL4 expression on uNK cells in human pregnancy.","date":"2007","source":"American journal of reproductive immunology (New York, N.Y. : 1989)","url":"https://pubmed.ncbi.nlm.nih.gov/17362384","citation_count":46,"is_preprint":false},{"pmid":"26791471","id":"PMC_26791471","title":"Increased uNK Progenitor Cells in Women With Endometriosis and Infertility are Associated With Low Levels of Endometrial Stem Cell Factor.","date":"2016","source":"American journal of reproductive immunology (New York, N.Y. : 1989)","url":"https://pubmed.ncbi.nlm.nih.gov/26791471","citation_count":43,"is_preprint":false},{"pmid":"27214130","id":"PMC_27214130","title":"Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure.","date":"2016","source":"Journal of reproductive immunology","url":"https://pubmed.ncbi.nlm.nih.gov/27214130","citation_count":39,"is_preprint":false},{"pmid":"31825483","id":"PMC_31825483","title":"Endometrial uNK cell counts do not predict successful implantation in an IVF population.","date":"2019","source":"Human reproduction (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/31825483","citation_count":36,"is_preprint":false},{"pmid":"26985000","id":"PMC_26985000","title":"The Transcription Factor NFIL3 Is Essential for Normal Placental and Embryonic Development but Not for Uterine Natural Killer (UNK) Cell Differentiation in Mice.","date":"2016","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/26985000","citation_count":28,"is_preprint":false},{"pmid":"22206676","id":"PMC_22206676","title":"Decidual spiral artery remodeling during early post-implantation period in mice: investigation of associations with decidual uNK cells and invasive trophoblast.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/22206676","citation_count":27,"is_preprint":false},{"pmid":"31099432","id":"PMC_31099432","title":"uNK cell-derived TGF-β1 regulates the long noncoding RNA MEG3 to control vascular smooth muscle cell migration and apoptosis in spiral artery remodeling.","date":"2019","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31099432","citation_count":20,"is_preprint":false},{"pmid":"24396391","id":"PMC_24396391","title":"Effects of Acupuncture on CCL2 and CXCL8 Expression and the Subset of uNK Cells in Rats with Embryo Implantation Failure.","date":"2013","source":"Evidence-based complementary and alternative medicine : eCAM","url":"https://pubmed.ncbi.nlm.nih.gov/24396391","citation_count":14,"is_preprint":false},{"pmid":"22884101","id":"PMC_22884101","title":"The correlation of autoantibodies and uNK cells in women with reproductive failure.","date":"2012","source":"Journal of reproductive immunology","url":"https://pubmed.ncbi.nlm.nih.gov/22884101","citation_count":12,"is_preprint":false},{"pmid":"28098245","id":"PMC_28098245","title":"Natural cytotoxicity receptor 1 in mouse uNK cell maturation and function.","date":"2017","source":"Mucosal immunology","url":"https://pubmed.ncbi.nlm.nih.gov/28098245","citation_count":11,"is_preprint":false},{"pmid":"25085343","id":"PMC_25085343","title":"Rat spontaneous foetal resorption: altered α2-macroglobulin levels and uNK cell number.","date":"2014","source":"Histochemistry and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25085343","citation_count":11,"is_preprint":false},{"pmid":"27452436","id":"PMC_27452436","title":"COX-2 plays a role in angiogenic DBA(+) uNK cell subsets activation and pregnancy protection in LPS-exposed mice.","date":"2016","source":"Placenta","url":"https://pubmed.ncbi.nlm.nih.gov/27452436","citation_count":8,"is_preprint":false},{"pmid":"21223424","id":"PMC_21223424","title":"Effect of human endometrial stromal cell-derived conditioned medium on uterine natural killer (uNK) cells' proliferation and cytotoxicity.","date":"2011","source":"American journal of reproductive immunology (New York, N.Y. : 1989)","url":"https://pubmed.ncbi.nlm.nih.gov/21223424","citation_count":8,"is_preprint":false},{"pmid":"23414625","id":"PMC_23414625","title":"A rapid, reliable method for uNK cell density estimation.","date":"2013","source":"Journal of reproductive immunology","url":"https://pubmed.ncbi.nlm.nih.gov/23414625","citation_count":7,"is_preprint":false},{"pmid":"20201059","id":"PMC_20201059","title":"Immunocytochemical studies of adhesion molecules on mouse UNK cells and their extracellular matrix ligands during mouse pregnancy.","date":"2010","source":"Anatomical record (Hoboken, N.J. : 2007)","url":"https://pubmed.ncbi.nlm.nih.gov/20201059","citation_count":6,"is_preprint":false},{"pmid":"38009057","id":"PMC_38009057","title":"Decreased CD56+CD16-CD94+uNK cells in the mid-luteal phase in women with recurrent implantation failure are associated with IL-15 deficiency.","date":"2023","source":"American journal of reproductive immunology (New York, N.Y. : 1989)","url":"https://pubmed.ncbi.nlm.nih.gov/38009057","citation_count":5,"is_preprint":false},{"pmid":"32763974","id":"PMC_32763974","title":"A potential role for a novel ZC3H5 complex in regulating mRNA translation in Trypanosoma brucei.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32763974","citation_count":4,"is_preprint":false},{"pmid":"30841066","id":"PMC_30841066","title":"Identification of Rhizoctonia solani AG-UNK from Rice and Rice Fields in Texas as AG-11.","date":"1999","source":"Plant disease","url":"https://pubmed.ncbi.nlm.nih.gov/30841066","citation_count":4,"is_preprint":false},{"pmid":"32626772","id":"PMC_32626772","title":"UL16-Binding Protein 1 Induced HTR-8/SVneo Autophagy via NF-κB Suppression Mediated by TNF-α Secreted through uNK Cells.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/32626772","citation_count":4,"is_preprint":false},{"pmid":"28531818","id":"PMC_28531818","title":"Pharmacophore searching: A potential solution for correcting unknown ligands (UNK) labelling errors in Protein Data Bank (PDB'S).","date":"2017","source":"Journal of molecular graphics & modelling","url":"https://pubmed.ncbi.nlm.nih.gov/28531818","citation_count":2,"is_preprint":false},{"pmid":"20146644","id":"PMC_20146644","title":"ALkappa(I) (UNK) - primary structure of an AL-amyloid protein presenting an organ-limited subcutaneous nodular amyloid syndrome of long duration. Case report and review.","date":"2010","source":"Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis","url":"https://pubmed.ncbi.nlm.nih.gov/20146644","citation_count":1,"is_preprint":false},{"pmid":"40575442","id":"PMC_40575442","title":"Depletion of UNK-1 affects head locomotive behaviors in Caenorhabditis elegans.","date":"2025","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/40575442","citation_count":0,"is_preprint":false},{"pmid":"41297357","id":"PMC_41297357","title":"Impaired placental vascular remodeling and persistent uNK cells in the RUPP model: A time-dependent perspective.","date":"2025","source":"Placenta","url":"https://pubmed.ncbi.nlm.nih.gov/41297357","citation_count":0,"is_preprint":false},{"pmid":"39276273","id":"PMC_39276273","title":"High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells.","date":"2024","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39276273","citation_count":0,"is_preprint":false},{"pmid":"41936274","id":"PMC_41936274","title":"Endometrial microbiota in maternal-fetal tolerance: An in vitro study of extravillous trophoblasts and uNK cells.","date":"2026","source":"Journal of reproductive immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41936274","citation_count":0,"is_preprint":false},{"pmid":"42192073","id":"PMC_42192073","title":"The Impact of the Number of Implantation-Window uNK Cells on Pregnancy Outcomes and Decidualization.","date":"2026","source":"Reproductive sciences (Thousand Oaks, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/42192073","citation_count":0,"is_preprint":false},{"pmid":"42034590","id":"PMC_42034590","title":"Exposure to glyphosate-based herbicide impairs uterine decidualization via disruption of autophagy-adhesion molecules-uNK cell residence in mice.","date":"2026","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/42034590","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.07.29.605660","title":"The Unkempt RNA binding protein reveals a local translation program in centriole overduplication","date":"2024-07-30","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.29.605660","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.05.663267","title":"A developmental program of early residency promotes the differentiation of divergent uterine NK cell subsets in humans","date":"2025-07-09","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.05.663267","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.11.07.622412","title":"Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage","date":"2024-11-08","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.07.622412","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.29.645626","title":"Eomesodermin defines uterine NK cells crucial for pregnancy success in mice","date":"2025-04-03","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.29.645626","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.25.605132","title":"The role of dietary patterns in the polarization of angiogenic uterine Natural Killer cells during murine pregnancy","date":"2024-07-25","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.25.605132","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.28.24316308","title":"Ayahuasca-Inspired DMT/HAR Formulation Reduces Brain Differentiation Between Self and Other Faces","date":"2024-11-01","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.28.24316308","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19615,"output_tokens":1014,"usd":0.037027,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7077,"output_tokens":1292,"usd":0.033842,"stage2_stop_reason":"end_turn"},"total_usd":0.070869,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the corpus, I need to identify papers about the canonical UNK gene (also known as KIAA1753, ZC3HDC5, ZC3H5) — an RNA-binding protein involved in translational regulation.\n\nThe vast majority of papers are about \"uNK\" = uterine Natural Killer cells, which is a completely different entity (an immune cell type, not a gene). These must be excluded.\n\nPaper [19] is about ZC3H5 in *Trypanosoma brucei* — this is a symbol collision with a trypanosome gene, not an ortholog of human UNK/ZC3H5. The protein domain architecture and cellular context differ fundamentally from the mammalian UNK RNA-binding protein.\n\nPaper [24] is about UNK-1/Unkempt in *C. elegans* — this is an ortholog of the mammalian UNK/Unkempt RNA-binding protein, consistent with the conserved RNA-binding protein function described in the corpus.\n\nPaper [30] (preprint) is about Unkempt (UNK) RNA-binding protein in mammalian cells — directly about the canonical gene.\n\nPapers [20], [22], [23], [35] are symbol collisions or irrelevant.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"In C. elegans, UNK-1 (ortholog of mammalian Unkempt/UNK) is expressed cytoplasmically in head neurons, and its depletion via an auxin-inducible degron system results in increased head oscillations, a phenotype associated with defects in neurotransmitter synthesis, linking UNK-1 to head motor control.\",\n      \"method\": \"Genome editing (auxin-inducible degron tag + mNeonGreen knock-in), live imaging for subcellular localization, targeted protein depletion with behavioral phenotypic readout\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with defined cellular/behavioral phenotype and direct localization, single study in C. elegans ortholog\",\n      \"pmids\": [\"40575442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Mammalian Unkempt (UNK) protein localizes to centrosomes and Cep131-positive centriolar satellites, and is required for Plk4-induced centriole overduplication in an RNA-binding-dependent manner. UNK interacts with CNOT9, a component of the translational inhibitory CCR4-NOT complex, which also localizes to centrosomes during early centrosome amplification. Centriolar satellites and UNK promote local translation at centrosomes, and a transient downregulation of centrosomal translation occurs early in Plk4-induced centrosome amplification.\",\n      \"method\": \"Immunofluorescence/localization studies, co-immunoprecipitation (UNK–CNOT9 interaction), RNA-binding-dependent functional rescue, loss-of-function analysis of centriole overduplication, proximity-ligation or translation reporters at centrosomes\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (localization, Co-IP, RNA-binding-dependent rescue, translation reporters) in a single preprint study; not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"UNK (Unkempt) is a conserved cytoplasmic RNA-binding protein that localizes to centrosomes and centriolar satellites in mammalian cells, where it interacts with the CCR4-NOT complex component CNOT9 and promotes local translation required for Plk4-induced centriole overduplication; in C. elegans, its ortholog UNK-1 is expressed in head neurons and controls head motor behavior, consistent with a role in neuronal translational regulation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"UNK (Unkempt) is a conserved cytoplasmic RNA-binding protein implicated in localized translational control in both centrosomal and neuronal contexts [#0, #1]. In mammalian cells, UNK localizes to centrosomes and Cep131-positive centriolar satellites and is required, in an RNA-binding-dependent manner, for Plk4-induced centriole overduplication; it interacts with the CCR4-NOT component CNOT9 and, together with centriolar satellites, promotes local translation at centrosomes during early centrosome amplification [#1]. In C. elegans, the ortholog UNK-1 is expressed cytoplasmically in head neurons, and its depletion increases head oscillations, linking UNK to head motor control consistent with a role in neuronal translational regulation [#0]. Beyond these contexts, the molecular targets of UNK-dependent translation and the structural basis of its RNA binding have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Established that mammalian UNK acts at the centrosome to support centriole biogenesis through RNA-binding-dependent local translation, identifying a physical link to the CCR4-NOT translational machinery.\",\n      \"evidence\": \"Immunofluorescence localization, UNK\\u2013CNOT9 co-immunoprecipitation, RNA-binding-dependent functional rescue, and translation reporters in mammalian cells (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific mRNA targets translated locally at centrosomes are not identified\",\n        \"Mechanism by which UNK is recruited to centriolar satellites is unknown\",\n        \"Not yet peer-reviewed and CNOT9 interaction rests on a single Co-IP without reciprocal validation\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated an in vivo neuronal function for the UNK ortholog, showing that UNK-1 in head neurons controls head motor behavior, consistent with translational regulation in a whole-organism context.\",\n      \"evidence\": \"Auxin-inducible degron depletion with mNeonGreen knock-in, live imaging, and behavioral readout in C. elegans\",\n      \"pmids\": [\n        \"40575442\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular targets of UNK-1 in head neurons are not defined\",\n        \"Link between the behavioral phenotype and translational/RNA-binding activity is inferred, not demonstrated\",\n        \"Single study in the C. elegans ortholog\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether UNK's centrosomal and neuronal functions reflect a single conserved translational-control mechanism, and the identity of its regulated mRNAs, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct RNA targets identified in either context\",\n        \"No structural model of UNK RNA recognition\",\n        \"Conservation of the centrosomal role into the C. elegans system untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"CNOT9\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":{"gene":"UNK","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"uncited_synthesis","uniprot_band":"medium","rules_fired":"R8","issue":"R8: 1/3 claims uncited (33%)"},"evaluation":{"pairwise":"loss","faith_supported":2,"faith_total":2,"faith_pct":100.0}}