{"gene":"ARID3C","run_date":"2026-04-28T17:12:37","timeline":{"discoveries":[{"year":2007,"finding":"ARID3C (Brightlike/ARID3c) contains a REKLES domain, shared only within the ARID3 subfamily, which mediates self-association, paralogue association, nuclear matrix targeting, and nucleocytoplasmic shuttling; REKLESbeta mediates interaction with ARID3A (Bright) and ARID3B (Bdp), and REKLESalpha/beta are required for nuclear import and Crm1-dependent nuclear export, respectively.","method":"Domain mutagenesis, nuclear-cytoplasmic fractionation, multimerization assays, DNA binding assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (mutagenesis, fractionation, DNA binding, multimerization assays) in a single study with strong mechanistic detail","pmids":["17400556"],"is_preprint":false},{"year":2011,"finding":"ARID3C (Brightlike) encodes two alternatively spliced isoforms that are SUMO-I-modified; the full-length isoform (but not the REKLES-deleted Δ6 isoform) undergoes nuclear-cytoplasmic shuttling, localizes to lipid rafts upon BCR stimulation, associates with ARID3A (Bright) in solution and at common DNA binding sites in vitro, and co-activates ARID3A-dependent immunoglobulin heavy chain (IgH) transcription, with maximal activity mediated by the unsumoylated form.","method":"Alternative splicing characterization, SUMO modification assay, co-immunoprecipitation, in vitro DNA binding, chromatin immunoprecipitation (ChIP), transcription reporter assays, subcellular fractionation/localization","journal":"Molecular immunology","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (Co-IP, ChIP, in vitro DNA binding, reporter assays, localization) establishing mechanism in a single study","pmids":["21955986"],"is_preprint":false},{"year":2024,"finding":"ARID3C binds NPM1 to facilitate nuclear translocation; once in the nucleus, ARID3C acts as a transcription factor for STAT3, STAT1, and JUNB promoters to drive monocyte-to-macrophage differentiation. Mutation of the ARID3C–NPM1 binding interface (predicted by AlphaFold2) prevents nuclear import, retaining ARID3C in the cytoplasm and abolishing target gene activation and differentiation.","method":"LC-MS/MS interactome, co-immunoprecipitation, subcellular localization (imaging/fractionation), site-directed mutagenesis, chromatin immunoprecipitation, AlphaFold2 structural prediction, loss-of-function differentiation assay","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (MS, Co-IP, ChIP, mutagenesis, localization) in a single lab study; structural prediction is computational","pmids":["38231884"],"is_preprint":false},{"year":2019,"finding":"ARID3C was identified as part of a signaling complex with PTPRR, α-catenin, β-catenin, and E-cadherin in ovarian cancer cells, placing ARID3C in the Wnt/β-catenin pathway nexus.","method":"Proximity-based tagging (BioID) and RNA-Seq, proximity ligation assay","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 — proximity tagging identifies ARID3C as a complex component but no direct functional follow-up on ARID3C itself","pmids":["31653698"],"is_preprint":false},{"year":2024,"finding":"In mouse embryonic spinal cord, Arid3c marks an uncharacterized subset of V2 interneurons partially overlapping with V2c interneurons; conditional inactivation of Arid3c does not alter V2 neuron production but causes minor locomotor execution defects, suggesting a role in locomotor circuit formation rather than neuronal fate specification.","method":"Transcriptome comparison, in situ hybridization/immunostaining, Arid3c knockout mouse with locomotor behavioral readout","journal":"Frontiers in cellular neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined behavioral/cellular phenotype; consistent with mammalian ARID3C biology","pmids":["39479525"],"is_preprint":false}],"current_model":"ARID3C is an ARID3-subfamily transcription factor that uses its REKLES domain for nucleocytoplasmic shuttling, SUMO modification, and heterodimerization with ARID3A; it recruits NPM1 for nuclear import, co-activates ARID3A-dependent immunoglobulin heavy chain transcription in B cells, drives monocyte-to-macrophage differentiation by activating STAT3/STAT1/JUNB, and participates in a Wnt/β-catenin-associated signaling complex in epithelial cells."},"narrative":{"teleology":[{"year":2007,"claim":"Establishing that ARID3C possesses a functional REKLES domain resolved how this newly identified paralogue achieves nuclear-cytoplasmic shuttling and interacts with ARID3A/3B, defining it as a bona fide ARID3 subfamily member with distinct domain-dependent trafficking.","evidence":"Domain mutagenesis, nuclear-cytoplasmic fractionation, multimerization and DNA binding assays in transfected cells","pmids":["17400556"],"confidence":"High","gaps":["No endogenous physiological context for ARID3C function was established","Whether ARID3C directly binds DNA at specific genomic targets was not resolved","Mechanism of nuclear import partner recruitment unknown"]},{"year":2011,"claim":"Demonstrating that ARID3C co-occupies immunoglobulin heavy chain regulatory elements with ARID3A and co-activates IgH transcription established a direct transcriptional role in B-cell biology, while revealing SUMO-I modification as a negative regulatory mechanism.","evidence":"Co-IP, ChIP, in vitro DNA binding, transcription reporter assays, SUMO modification assay, and subcellular fractionation in B-cell lines","pmids":["21955986"],"confidence":"High","gaps":["Whether ARID3C is required for IgH expression in vivo (e.g., knockout B cells) was not tested","Mechanism by which SUMO modification suppresses transcriptional co-activation is unknown","Lipid raft relocalization upon BCR stimulation was not functionally linked to transcriptional output"]},{"year":2019,"claim":"Proximity-based identification of ARID3C in a complex with β-catenin, α-catenin, E-cadherin, and PTPRR in ovarian cancer cells raised the possibility of a role at the Wnt/β-catenin–cell adhesion interface, though no direct functional follow-up on ARID3C was performed.","evidence":"BioID proximity tagging and proximity ligation assay in ovarian cancer cells","pmids":["31653698"],"confidence":"Low","gaps":["No direct functional validation of ARID3C within this complex was performed","Whether ARID3C modulates Wnt/β-catenin signaling output is untested","Proximity labeling does not confirm direct physical interaction"]},{"year":2024,"claim":"Identification of NPM1 as the nuclear import chaperone for ARID3C, and demonstration that ARID3C directly activates STAT3/STAT1/JUNB promoters during macrophage differentiation, extended its transcription factor role beyond B cells into myeloid lineage commitment.","evidence":"LC-MS/MS interactome, co-IP, site-directed mutagenesis of NPM1 binding interface, ChIP, subcellular fractionation, and loss-of-function differentiation assays in monocytic cells","pmids":["38231884"],"confidence":"Medium","gaps":["AlphaFold2-predicted binding interface awaits experimental structural validation","Whether NPM1-dependent import also operates in B cells or other lineages is unknown","In vivo requirement for ARID3C in myeloid differentiation has not been tested"]},{"year":2024,"claim":"Conditional knockout of Arid3c in mouse spinal cord revealed a role in locomotor circuit formation without affecting neuronal fate specification, extending ARID3C function to neurodevelopment.","evidence":"Arid3c conditional knockout mouse, in situ hybridization, immunostaining, and locomotor behavioral analysis","pmids":["39479525"],"confidence":"Medium","gaps":["Transcriptional targets of ARID3C in spinal interneurons are unidentified","Whether the locomotor phenotype reflects cell-autonomous transcriptional activity or non-autonomous signaling is unclear","The V2 interneuron subset marked by Arid3c remains molecularly uncharacterized"]},{"year":null,"claim":"The genome-wide direct target repertoire of ARID3C across cell types, the structural basis of its DNA binding and NPM1 interaction, and whether its myeloid and neural functions depend on the same REKLES-mediated partnerships as in B cells remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No genome-wide binding profile (ChIP-seq) exists for ARID3C in any cell type","No crystal or cryo-EM structure of ARID3C or its complexes has been determined","Functional relationship between ARID3C's roles in B cells, macrophages, neurons, and epithelial Wnt signaling is unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[0,1]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[1,2]}],"complexes":[],"partners":["ARID3A","ARID3B","NPM1"],"other_free_text":[]},"mechanistic_narrative":"ARID3C is an ARID3-subfamily transcription factor whose REKLES domain mediates self-association, heterodimerization with ARID3A and ARID3B, nuclear matrix targeting, and CRM1-dependent nucleocytoplasmic shuttling [PMID:17400556]. In B cells, ARID3C co-activates ARID3A-dependent immunoglobulin heavy chain transcription, with maximal activity conferred by its unsumoylated form, and relocalizes to lipid rafts upon BCR stimulation [PMID:21955986]. In myeloid cells, ARID3C binds NPM1 to gain nuclear entry, where it directly activates STAT3, STAT1, and JUNB promoters to drive monocyte-to-macrophage differentiation [PMID:38231884]."},"prefetch_data":{"uniprot":{"accession":"A6NKF2","full_name":"AT-rich interactive domain-containing protein 3C","aliases":[],"length_aa":412,"mass_kda":44.1,"function":"Transcription factor involved in monocyte-to-macrophage differentiation. Forms a complex with NPM1 to translocate to the nucleus, acting as a transcription factor that promotes the expression of the genes involved in macrophage differentiation, such as STAT3, STAT1 and JUNB","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/A6NKF2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ARID3C","classification":"Not Classified","n_dependent_lines":12,"n_total_lines":1208,"dependency_fraction":0.009933774834437087},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ARID3C","total_profiled":1310},"omim":[{"mim_id":"620868","title":"AT-RICH INTERACTION DOMAIN-CONTAINING PROTEIN 3C; ARID3C","url":"https://www.omim.org/entry/620868"},{"mim_id":"603265","title":"AT-RICH INTERACTION DOMAIN-CONTAINING PROTEIN 3A; ARID3A","url":"https://www.omim.org/entry/603265"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in single","driving_tissues":[{"tissue":"liver","ntpm":10.0}],"url":"https://www.proteinatlas.org/search/ARID3C"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"A6NKF2","domains":[{"cath_id":"1.10.150.60","chopping":"101-223","consensus_level":"medium","plddt":95.1212,"start":101,"end":223}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NKF2","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6NKF2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6NKF2-F1-predicted_aligned_error_v6.png","plddt_mean":65.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ARID3C","jax_strain_url":"https://www.jax.org/strain/search?query=ARID3C"},"sequence":{"accession":"A6NKF2","fasta_url":"https://rest.uniprot.org/uniprotkb/A6NKF2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6NKF2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NKF2"}},"corpus_meta":[{"pmid":"17400556","id":"PMC_17400556","title":"REKLES is an ARID3-restricted multifunctional domain.","date":"2007","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17400556","citation_count":26,"is_preprint":false},{"pmid":"21955986","id":"PMC_21955986","title":"Characterization of a new ARID family transcription factor (Brightlike/ARID3C) that co-activates Bright/ARID3A-mediated immunoglobulin gene transcription.","date":"2011","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21955986","citation_count":22,"is_preprint":false},{"pmid":"24704276","id":"PMC_24704276","title":"Differential expression of ARID3B in normal adult tissue and carcinomas.","date":"2014","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/24704276","citation_count":19,"is_preprint":false},{"pmid":"31653698","id":"PMC_31653698","title":"Protein tyrosine phosphatase receptor type R (PTPRR) antagonizes the Wnt signaling pathway in ovarian cancer by dephosphorylating and inactivating β-catenin.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31653698","citation_count":17,"is_preprint":false},{"pmid":"35127746","id":"PMC_35127746","title":"Expression Signature of the AT-Rich Interactive Domain Gene Family Identified in Digestive Cancer.","date":"2022","source":"Frontiers in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35127746","citation_count":5,"is_preprint":false},{"pmid":"38231884","id":"PMC_38231884","title":"ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differentiation Interacting with NPM1.","date":"2024","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/38231884","citation_count":2,"is_preprint":false},{"pmid":"40654017","id":"PMC_40654017","title":"DNA-Methylation for Risk-Stratification of Women Without a Fully Visible Transformation Zone at Colposcopy: A Cross-Sectional Study.","date":"2025","source":"BJOG : an international journal of obstetrics and gynaecology","url":"https://pubmed.ncbi.nlm.nih.gov/40654017","citation_count":2,"is_preprint":false},{"pmid":"39479525","id":"PMC_39479525","title":"Arid3c identifies an uncharacterized subpopulation of V2 interneurons during embryonic spinal cord development.","date":"2024","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/39479525","citation_count":1,"is_preprint":false},{"pmid":"38958822","id":"PMC_38958822","title":"Identification of Single-Nucleotide Polymorphisms in Differentially Expressed Genes Favoring Soybean Meal Tolerance in Higher-Growth Zebrafish (Danio rerio).","date":"2024","source":"Marine biotechnology (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/38958822","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6222,"output_tokens":1451,"usd":0.020216},"stage2":{"model":"claude-opus-4-6","input_tokens":4692,"output_tokens":1799,"usd":0.102652},"total_usd":0.122868,"stage1_batch_id":"msgbatch_01TqNM6p6FsoMBT2jzQTwKBr","stage2_batch_id":"msgbatch_01Ya473eco8sTHbvRymQaU8o","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"ARID3C (Brightlike/ARID3c) contains a REKLES domain, shared only within the ARID3 subfamily, which mediates self-association, paralogue association, nuclear matrix targeting, and nucleocytoplasmic shuttling; REKLESbeta mediates interaction with ARID3A (Bright) and ARID3B (Bdp), and REKLESalpha/beta are required for nuclear import and Crm1-dependent nuclear export, respectively.\",\n      \"method\": \"Domain mutagenesis, nuclear-cytoplasmic fractionation, multimerization assays, DNA binding assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (mutagenesis, fractionation, DNA binding, multimerization assays) in a single study with strong mechanistic detail\",\n      \"pmids\": [\"17400556\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ARID3C (Brightlike) encodes two alternatively spliced isoforms that are SUMO-I-modified; the full-length isoform (but not the REKLES-deleted Δ6 isoform) undergoes nuclear-cytoplasmic shuttling, localizes to lipid rafts upon BCR stimulation, associates with ARID3A (Bright) in solution and at common DNA binding sites in vitro, and co-activates ARID3A-dependent immunoglobulin heavy chain (IgH) transcription, with maximal activity mediated by the unsumoylated form.\",\n      \"method\": \"Alternative splicing characterization, SUMO modification assay, co-immunoprecipitation, in vitro DNA binding, chromatin immunoprecipitation (ChIP), transcription reporter assays, subcellular fractionation/localization\",\n      \"journal\": \"Molecular immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (Co-IP, ChIP, in vitro DNA binding, reporter assays, localization) establishing mechanism in a single study\",\n      \"pmids\": [\"21955986\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ARID3C binds NPM1 to facilitate nuclear translocation; once in the nucleus, ARID3C acts as a transcription factor for STAT3, STAT1, and JUNB promoters to drive monocyte-to-macrophage differentiation. Mutation of the ARID3C–NPM1 binding interface (predicted by AlphaFold2) prevents nuclear import, retaining ARID3C in the cytoplasm and abolishing target gene activation and differentiation.\",\n      \"method\": \"LC-MS/MS interactome, co-immunoprecipitation, subcellular localization (imaging/fractionation), site-directed mutagenesis, chromatin immunoprecipitation, AlphaFold2 structural prediction, loss-of-function differentiation assay\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (MS, Co-IP, ChIP, mutagenesis, localization) in a single lab study; structural prediction is computational\",\n      \"pmids\": [\"38231884\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ARID3C was identified as part of a signaling complex with PTPRR, α-catenin, β-catenin, and E-cadherin in ovarian cancer cells, placing ARID3C in the Wnt/β-catenin pathway nexus.\",\n      \"method\": \"Proximity-based tagging (BioID) and RNA-Seq, proximity ligation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — proximity tagging identifies ARID3C as a complex component but no direct functional follow-up on ARID3C itself\",\n      \"pmids\": [\"31653698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In mouse embryonic spinal cord, Arid3c marks an uncharacterized subset of V2 interneurons partially overlapping with V2c interneurons; conditional inactivation of Arid3c does not alter V2 neuron production but causes minor locomotor execution defects, suggesting a role in locomotor circuit formation rather than neuronal fate specification.\",\n      \"method\": \"Transcriptome comparison, in situ hybridization/immunostaining, Arid3c knockout mouse with locomotor behavioral readout\",\n      \"journal\": \"Frontiers in cellular neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined behavioral/cellular phenotype; consistent with mammalian ARID3C biology\",\n      \"pmids\": [\"39479525\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ARID3C is an ARID3-subfamily transcription factor that uses its REKLES domain for nucleocytoplasmic shuttling, SUMO modification, and heterodimerization with ARID3A; it recruits NPM1 for nuclear import, co-activates ARID3A-dependent immunoglobulin heavy chain transcription in B cells, drives monocyte-to-macrophage differentiation by activating STAT3/STAT1/JUNB, and participates in a Wnt/β-catenin-associated signaling complex in epithelial cells.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ARID3C is an ARID3-subfamily transcription factor whose REKLES domain mediates self-association, heterodimerization with ARID3A and ARID3B, nuclear matrix targeting, and CRM1-dependent nucleocytoplasmic shuttling [PMID:17400556]. In B cells, ARID3C co-activates ARID3A-dependent immunoglobulin heavy chain transcription, with maximal activity conferred by its unsumoylated form, and relocalizes to lipid rafts upon BCR stimulation [PMID:21955986]. In myeloid cells, ARID3C binds NPM1 to gain nuclear entry, where it directly activates STAT3, STAT1, and JUNB promoters to drive monocyte-to-macrophage differentiation [PMID:38231884].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Establishing that ARID3C possesses a functional REKLES domain resolved how this newly identified paralogue achieves nuclear-cytoplasmic shuttling and interacts with ARID3A/3B, defining it as a bona fide ARID3 subfamily member with distinct domain-dependent trafficking.\",\n      \"evidence\": \"Domain mutagenesis, nuclear-cytoplasmic fractionation, multimerization and DNA binding assays in transfected cells\",\n      \"pmids\": [\"17400556\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No endogenous physiological context for ARID3C function was established\",\n        \"Whether ARID3C directly binds DNA at specific genomic targets was not resolved\",\n        \"Mechanism of nuclear import partner recruitment unknown\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrating that ARID3C co-occupies immunoglobulin heavy chain regulatory elements with ARID3A and co-activates IgH transcription established a direct transcriptional role in B-cell biology, while revealing SUMO-I modification as a negative regulatory mechanism.\",\n      \"evidence\": \"Co-IP, ChIP, in vitro DNA binding, transcription reporter assays, SUMO modification assay, and subcellular fractionation in B-cell lines\",\n      \"pmids\": [\"21955986\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ARID3C is required for IgH expression in vivo (e.g., knockout B cells) was not tested\",\n        \"Mechanism by which SUMO modification suppresses transcriptional co-activation is unknown\",\n        \"Lipid raft relocalization upon BCR stimulation was not functionally linked to transcriptional output\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Proximity-based identification of ARID3C in a complex with β-catenin, α-catenin, E-cadherin, and PTPRR in ovarian cancer cells raised the possibility of a role at the Wnt/β-catenin–cell adhesion interface, though no direct functional follow-up on ARID3C was performed.\",\n      \"evidence\": \"BioID proximity tagging and proximity ligation assay in ovarian cancer cells\",\n      \"pmids\": [\"31653698\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct functional validation of ARID3C within this complex was performed\",\n        \"Whether ARID3C modulates Wnt/β-catenin signaling output is untested\",\n        \"Proximity labeling does not confirm direct physical interaction\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identification of NPM1 as the nuclear import chaperone for ARID3C, and demonstration that ARID3C directly activates STAT3/STAT1/JUNB promoters during macrophage differentiation, extended its transcription factor role beyond B cells into myeloid lineage commitment.\",\n      \"evidence\": \"LC-MS/MS interactome, co-IP, site-directed mutagenesis of NPM1 binding interface, ChIP, subcellular fractionation, and loss-of-function differentiation assays in monocytic cells\",\n      \"pmids\": [\"38231884\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"AlphaFold2-predicted binding interface awaits experimental structural validation\",\n        \"Whether NPM1-dependent import also operates in B cells or other lineages is unknown\",\n        \"In vivo requirement for ARID3C in myeloid differentiation has not been tested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Conditional knockout of Arid3c in mouse spinal cord revealed a role in locomotor circuit formation without affecting neuronal fate specification, extending ARID3C function to neurodevelopment.\",\n      \"evidence\": \"Arid3c conditional knockout mouse, in situ hybridization, immunostaining, and locomotor behavioral analysis\",\n      \"pmids\": [\"39479525\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Transcriptional targets of ARID3C in spinal interneurons are unidentified\",\n        \"Whether the locomotor phenotype reflects cell-autonomous transcriptional activity or non-autonomous signaling is unclear\",\n        \"The V2 interneuron subset marked by Arid3c remains molecularly uncharacterized\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The genome-wide direct target repertoire of ARID3C across cell types, the structural basis of its DNA binding and NPM1 interaction, and whether its myeloid and neural functions depend on the same REKLES-mediated partnerships as in B cells remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No genome-wide binding profile (ChIP-seq) exists for ARID3C in any cell type\",\n        \"No crystal or cryo-EM structure of ARID3C or its complexes has been determined\",\n        \"Functional relationship between ARID3C's roles in B cells, macrophages, neurons, and epithelial Wnt signaling is unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0074160\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ARID3A\",\n      \"ARID3B\",\n      \"NPM1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}