{"gene":"ACTR3B","run_date":"2026-06-09T22:02:40","timeline":{"discoveries":[{"year":2000,"finding":"ARP3beta (ACTR3B) is a second isoform of the human ARP3 subfamily, highly conserved with ARP3. It is predominantly expressed in neurons and epithelial cells of the choroid plexus in brain, as shown by Northern blotting and in situ hybridization. Alternative splicing causing exon 2 skipping produces truncated protein isoforms. In contrast to ARP3, which is ubiquitously expressed, ACTR3B expression is restricted to specific neural and epithelial cell types.","method":"cDNA cloning, Northern blotting, in situ hybridization, gene structure analysis, chromosomal mapping","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal methods (Northern blot, ISH, gene structure) in a single study establishing tissue-restricted expression and alternative splicing, but no functional assay for the protein itself","pmids":["10806390"],"is_preprint":false},{"year":2024,"finding":"ACTR3B is a transcriptional target of the NSD1 alternative isoform AT2 (NSD1 Δ5Δ7). siRNA knockdown of NSD1 isoforms (canonical and AT2) in fibroblasts caused loss of ACTR3B expression, impaired actin cytoskeleton regulation, and selective loss of stress fibers, establishing that NSD1-AT2 → ACTR3B signaling is required for stress fiber formation.","method":"siRNA knockdown of NSD1 isoforms, Western blotting, transcriptome analysis, actin cytoskeleton phenotyping in fibroblasts","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with defined cellular phenotype (stress fiber loss) and transcriptome data linking NSD1-AT2 to ACTR3B, single lab, two orthogonal methods (proteomics + transcriptomics)","pmids":["39336709"],"is_preprint":false},{"year":2019,"finding":"In colorectal cancer cells, ACTR3B expression is directly suppressed by miR-497-5p (established by luciferase reporter assay). Knockdown of ACTR3B (siACTR3B) reduced CRC cell proliferation, migration, and invasion, placing ACTR3B downstream of the lncRNA AC009022.1 / miR-497-5p axis in promoting these phenotypes.","method":"Luciferase reporter gene assay, siRNA knockdown, cell proliferation assay, scratch/migration assay, Transwell invasion assay, Western blot, qRT-PCR","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter confirms direct miR-497-5p targeting of ACTR3B, KD with multiple cellular phenotype readouts, single lab","pmids":["31637768"],"is_preprint":false}],"current_model":"ACTR3B (ARP3beta) is a neuronally enriched isoform of the ARP3 actin-related protein family whose expression is directly regulated by the NSD1-AT2 transcriptional isoform and by miR-497-5p, and whose activity is required for actin stress fiber formation in fibroblasts and for proliferation, migration, and invasion in colorectal cancer cells."},"narrative":{"mechanistic_narrative":"ACTR3B (ARP3beta) is a tissue-restricted isoform of the ARP3 actin-related protein subfamily, expressed predominantly in neurons and choroid plexus epithelial cells in contrast to the ubiquitously expressed ARP3, and subject to alternative splicing that yields truncated protein isoforms [PMID:10806390]. Functionally, ACTR3B participates in actin cytoskeleton organization: its expression is driven by the NSD1 alternative isoform AT2, and loss of this NSD1-AT2 → ACTR3B axis abolishes actin stress fiber formation in fibroblasts [PMID:39336709]. In colorectal cancer cells, ACTR3B is a direct target of miR-497-5p, and its activity supports cell proliferation, migration, and invasion [PMID:31637768]. Beyond these transcriptional and phenotypic links, the biochemical mechanism by which ACTR3B acts on actin has not been characterized in the available corpus.","teleology":[{"year":2000,"claim":"Established that the human ARP3 subfamily contains a second, distinct isoform (ACTR3B/ARP3beta) with a tissue-restricted expression pattern, distinguishing it from the ubiquitous ARP3.","evidence":"cDNA cloning, Northern blotting, in situ hybridization, and gene structure analysis in human tissues","pmids":["10806390"],"confidence":"Medium","gaps":["No functional assay for the protein itself","Role of exon-2-skipped truncated isoforms not defined","No demonstration of actin-related or Arp2/3-complex activity"]},{"year":2019,"claim":"Placed ACTR3B as a functional effector promoting malignant phenotypes, downstream of a regulatory miRNA, by showing direct miR-497-5p targeting and knockdown effects on tumor cell behavior.","evidence":"Luciferase reporter assay, siRNA knockdown with proliferation, migration, and invasion readouts in colorectal cancer cells","pmids":["31637768"],"confidence":"Medium","gaps":["Molecular mechanism by which ACTR3B drives migration/invasion not resolved","Single lab and single cancer context","No biochemical link to actin polymerization machinery"]},{"year":2024,"claim":"Identified a transcriptional regulator of ACTR3B and connected it to a defined cytoskeletal phenotype, establishing that ACTR3B expression is required for actin stress fiber formation.","evidence":"siRNA knockdown of NSD1 isoforms with transcriptome analysis and actin cytoskeleton phenotyping in fibroblasts","pmids":["39336709"],"confidence":"Medium","gaps":["Direct biochemical action of ACTR3B on stress fiber assembly not shown","Whether ACTR3B regulation by NSD1-AT2 is direct or indirect not established","No structural or interaction data"]},{"year":null,"claim":"The direct biochemical activity of ACTR3B on actin and its molecular partners remain undefined.","evidence":"No timeline discovery addresses ACTR3B's molecular interactions or enzymatic role","pmids":[],"confidence":"Low","gaps":["No evidence of incorporation into or function within an actin-nucleating complex","No identified direct protein partners","No structural characterization"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9P1U1","full_name":"Actin-related protein 3B","aliases":["ARP3-beta","Actin-like protein 3B","Actin-related protein ARP4"],"length_aa":418,"mass_kda":47.6,"function":"Plays a role in the organization of the actin cytoskeleton. May function as ATP-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. May decrease the metastatic potential of tumors","subcellular_location":"Cytoplasm, cytoskeleton; Cell projection","url":"https://www.uniprot.org/uniprotkb/Q9P1U1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ACTR3B","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"ACTR2","stoichiometry":0.2},{"gene":"ARPC2","stoichiometry":0.2},{"gene":"ARPC3","stoichiometry":0.2},{"gene":"CALD1","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"ENO1","stoichiometry":0.2},{"gene":"SEPT9","stoichiometry":0.2},{"gene":"STK4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/ACTR3B","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":51.8}],"url":"https://www.proteinatlas.org/search/ACTR3B"},"hgnc":{"alias_symbol":["ARP11","ARP3beta"],"prev_symbol":[]},"alphafold":{"accession":"Q9P1U1","domains":[{"cath_id":"3.30.420.40","chopping":"7-144_372-407","consensus_level":"high","plddt":91.5981,"start":7,"end":407},{"cath_id":"3.30.420.40","chopping":"155-194_294-367","consensus_level":"high","plddt":95.0822,"start":155,"end":367},{"cath_id":"3.90.640.10","chopping":"196-281","consensus_level":"high","plddt":96.2465,"start":196,"end":281}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P1U1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P1U1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P1U1-F1-predicted_aligned_error_v6.png","plddt_mean":93.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ACTR3B","jax_strain_url":"https://www.jax.org/strain/search?query=ACTR3B"},"sequence":{"accession":"Q9P1U1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P1U1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P1U1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P1U1"}},"corpus_meta":[{"pmid":"10806390","id":"PMC_10806390","title":"ARP3beta, the gene encoding a new human actin-related protein, is alternatively spliced and predominantly expressed in brain neuronal cells.","date":"2000","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10806390","citation_count":25,"is_preprint":false},{"pmid":"32403311","id":"PMC_32403311","title":"A Data-Driven Review of the Genetic Factors of Pregnancy Complications.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32403311","citation_count":24,"is_preprint":false},{"pmid":"31637768","id":"PMC_31637768","title":"LncRNA AC009022.1 enhances colorectal cancer cells proliferation, migration, and invasion by promoting ACTR3B expression via suppressing miR-497-5p.","date":"2019","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31637768","citation_count":17,"is_preprint":false},{"pmid":"15176487","id":"PMC_15176487","title":"Derangement of hypothetical proteins in fetal Down's syndrome brain.","date":"2004","source":"Neurochemical research","url":"https://pubmed.ncbi.nlm.nih.gov/15176487","citation_count":13,"is_preprint":false},{"pmid":"35294083","id":"PMC_35294083","title":"High-fat, sucrose and salt-rich diet during rat spermatogenesis lead to the development of chronic kidney disease in the female offspring of the F2 generation.","date":"2022","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/35294083","citation_count":12,"is_preprint":false},{"pmid":"29061174","id":"PMC_29061174","title":"De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay, growth failure, distinctive facial features, and multiple congenital anomalies: a case report.","date":"2017","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29061174","citation_count":12,"is_preprint":false},{"pmid":"29936139","id":"PMC_29936139","title":"Immune Characteristics of Chinese Diffuse Large B-Cell Lymphoma Patients: Implications for Cancer Immunotherapies.","date":"2018","source":"EBioMedicine","url":"https://pubmed.ncbi.nlm.nih.gov/29936139","citation_count":11,"is_preprint":false},{"pmid":"36506940","id":"PMC_36506940","title":"Dawn-to-dusk dry fasting induces anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome in peripheral blood mononuclear cells in subjects with metabolic syndrome.","date":"2022","source":"Metabolism open","url":"https://pubmed.ncbi.nlm.nih.gov/36506940","citation_count":7,"is_preprint":false},{"pmid":"37995913","id":"PMC_37995913","title":"Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.","date":"2023","source":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","url":"https://pubmed.ncbi.nlm.nih.gov/37995913","citation_count":6,"is_preprint":false},{"pmid":"39336709","id":"PMC_39336709","title":"Impact of NSD1 Alternative Transcripts in Actin Filament Formation and Cellular Division Pathways in Fibroblasts.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/39336709","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8288,"output_tokens":943,"usd":0.019505,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7432,"output_tokens":1363,"usd":0.035618,"stage2_stop_reason":"end_turn"},"total_usd":0.055123,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"ARP3beta (ACTR3B) is a second isoform of the human ARP3 subfamily, highly conserved with ARP3. It is predominantly expressed in neurons and epithelial cells of the choroid plexus in brain, as shown by Northern blotting and in situ hybridization. Alternative splicing causing exon 2 skipping produces truncated protein isoforms. In contrast to ARP3, which is ubiquitously expressed, ACTR3B expression is restricted to specific neural and epithelial cell types.\",\n      \"method\": \"cDNA cloning, Northern blotting, in situ hybridization, gene structure analysis, chromosomal mapping\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal methods (Northern blot, ISH, gene structure) in a single study establishing tissue-restricted expression and alternative splicing, but no functional assay for the protein itself\",\n      \"pmids\": [\"10806390\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ACTR3B is a transcriptional target of the NSD1 alternative isoform AT2 (NSD1 Δ5Δ7). siRNA knockdown of NSD1 isoforms (canonical and AT2) in fibroblasts caused loss of ACTR3B expression, impaired actin cytoskeleton regulation, and selective loss of stress fibers, establishing that NSD1-AT2 → ACTR3B signaling is required for stress fiber formation.\",\n      \"method\": \"siRNA knockdown of NSD1 isoforms, Western blotting, transcriptome analysis, actin cytoskeleton phenotyping in fibroblasts\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with defined cellular phenotype (stress fiber loss) and transcriptome data linking NSD1-AT2 to ACTR3B, single lab, two orthogonal methods (proteomics + transcriptomics)\",\n      \"pmids\": [\"39336709\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In colorectal cancer cells, ACTR3B expression is directly suppressed by miR-497-5p (established by luciferase reporter assay). Knockdown of ACTR3B (siACTR3B) reduced CRC cell proliferation, migration, and invasion, placing ACTR3B downstream of the lncRNA AC009022.1 / miR-497-5p axis in promoting these phenotypes.\",\n      \"method\": \"Luciferase reporter gene assay, siRNA knockdown, cell proliferation assay, scratch/migration assay, Transwell invasion assay, Western blot, qRT-PCR\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter confirms direct miR-497-5p targeting of ACTR3B, KD with multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"31637768\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ACTR3B (ARP3beta) is a neuronally enriched isoform of the ARP3 actin-related protein family whose expression is directly regulated by the NSD1-AT2 transcriptional isoform and by miR-497-5p, and whose activity is required for actin stress fiber formation in fibroblasts and for proliferation, migration, and invasion in colorectal cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ACTR3B (ARP3beta) is a tissue-restricted isoform of the ARP3 actin-related protein subfamily, expressed predominantly in neurons and choroid plexus epithelial cells in contrast to the ubiquitously expressed ARP3, and subject to alternative splicing that yields truncated protein isoforms [#0]. Functionally, ACTR3B participates in actin cytoskeleton organization: its expression is driven by the NSD1 alternative isoform AT2, and loss of this NSD1-AT2 \\u2192 ACTR3B axis abolishes actin stress fiber formation in fibroblasts [#1]. In colorectal cancer cells, ACTR3B is a direct target of miR-497-5p, and its activity supports cell proliferation, migration, and invasion [#2]. Beyond these transcriptional and phenotypic links, the biochemical mechanism by which ACTR3B acts on actin has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established that the human ARP3 subfamily contains a second, distinct isoform (ACTR3B/ARP3beta) with a tissue-restricted expression pattern, distinguishing it from the ubiquitous ARP3.\",\n      \"evidence\": \"cDNA cloning, Northern blotting, in situ hybridization, and gene structure analysis in human tissues\",\n      \"pmids\": [\"10806390\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay for the protein itself\",\n        \"Role of exon-2-skipped truncated isoforms not defined\",\n        \"No demonstration of actin-related or Arp2/3-complex activity\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed ACTR3B as a functional effector promoting malignant phenotypes, downstream of a regulatory miRNA, by showing direct miR-497-5p targeting and knockdown effects on tumor cell behavior.\",\n      \"evidence\": \"Luciferase reporter assay, siRNA knockdown with proliferation, migration, and invasion readouts in colorectal cancer cells\",\n      \"pmids\": [\"31637768\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism by which ACTR3B drives migration/invasion not resolved\",\n        \"Single lab and single cancer context\",\n        \"No biochemical link to actin polymerization machinery\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified a transcriptional regulator of ACTR3B and connected it to a defined cytoskeletal phenotype, establishing that ACTR3B expression is required for actin stress fiber formation.\",\n      \"evidence\": \"siRNA knockdown of NSD1 isoforms with transcriptome analysis and actin cytoskeleton phenotyping in fibroblasts\",\n      \"pmids\": [\"39336709\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical action of ACTR3B on stress fiber assembly not shown\",\n        \"Whether ACTR3B regulation by NSD1-AT2 is direct or indirect not established\",\n        \"No structural or interaction data\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical activity of ACTR3B on actin and its molecular partners remain undefined.\",\n      \"evidence\": \"No timeline discovery addresses ACTR3B's molecular interactions or enzymatic role\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No evidence of incorporation into or function within an actin-nucleating complex\",\n        \"No identified direct protein partners\",\n        \"No structural characterization\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":3,"faith_pct":66.66666666666667}}