{"gene":"COMMD2","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2013,"finding":"COMMD2 (along with COMMD3–10) interacts with the epithelial sodium channel (ENaC), as demonstrated by interaction assays; the broader family interaction with ENaC was established, though functional follow-up was focused on COMMD3 and COMMD9.","method":"Protein interaction assays (Co-IP/pulldown reported for COMMD2–10 interacting with ENaC)","journal":"American journal of physiology. Renal physiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab pulldown/interaction assay; functional characterization was performed only for COMMD3 and COMMD9, not COMMD2 specifically","pmids":["23637203"],"is_preprint":false},{"year":2022,"finding":"RNA interference-mediated knockdown of COMMD2 suppressed proliferation and migration of bladder cancer (BLCA) and uterine corpus endometrial carcinoma (UCEC) cell lines, and GSEA analysis linked COMMD2 co-expression networks to E2F targets, G2-M checkpoint, and mitotic spindle pathways in BLCA.","method":"RNA interference (siRNA knockdown), CCK-8 proliferation assay, EdU assay, wound healing assay, transwell migration assay, GSEA","journal":"Cancer medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single-lab loss-of-function with defined cellular phenotype but no direct molecular mechanism or pathway placement beyond correlation; no rescue or epistasis experiment","pmids":["36205192"],"is_preprint":false}],"current_model":"COMMD2 physically interacts with the epithelial sodium channel ENaC (as part of the broader COMMD family), and its loss-of-function suppresses cancer cell proliferation and migration with transcriptomic links to E2F/G2-M checkpoint pathways, but the precise molecular mechanism by which COMMD2 exerts these effects remains undefined."},"narrative":{"mechanistic_narrative":"COMMD2 is a member of the COMMD protein family that has been physically linked to the epithelial sodium channel ENaC, where COMMD2 through COMMD10 were shown to interact with the channel in interaction assays [PMID:23637203]. In cancer cell models, RNA interference-mediated depletion of COMMD2 suppresses proliferation and migration of bladder and uterine endometrial carcinoma cells, with co-expression analysis connecting COMMD2 to E2F target, G2-M checkpoint, and mitotic spindle gene sets [PMID:36205192]. Beyond these correlative cellular phenotypes and the family-level ENaC interaction, the precise molecular mechanism of COMMD2 has not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Established that COMMD2, as part of the COMMD family, can physically associate with the epithelial sodium channel ENaC, placing it in proximity to ion-channel regulation.","evidence":"Co-IP/pulldown interaction assays for COMMD2-10 with ENaC","pmids":["23637203"],"confidence":"Low","gaps":["Functional follow-up was performed only for COMMD3 and COMMD9, not COMMD2 specifically","No demonstration that COMMD2 alters ENaC activity or trafficking","Interaction is reported at the family level without COMMD2-specific reciprocal validation"]},{"year":2022,"claim":"Showed that COMMD2 is required for cancer cell proliferation and migration and is transcriptionally correlated with cell-cycle programs, framing it as a candidate pro-proliferative factor.","evidence":"siRNA knockdown with CCK-8, EdU, wound healing and transwell assays plus GSEA in BLCA and UCEC cell lines","pmids":["36205192"],"confidence":"Low","gaps":["No direct molecular mechanism linking COMMD2 to E2F/G2-M pathways","No rescue or epistasis experiment to confirm specificity","Pathway associations are correlative co-expression signals, not causal placements"]},{"year":null,"claim":"The direct molecular function of COMMD2 and the mechanism connecting its physical interactions to its proliferative phenotype remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical activity assigned to COMMD2","No defined complex or stable subunit assignment","Mechanism linking ENaC interaction and cancer cell phenotype unresolved"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["ENAC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q86X83","full_name":"COMM domain-containing protein 2","aliases":[],"length_aa":199,"mass_kda":22.7,"function":"Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129). May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-kappa-B (PubMed:15799966)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q86X83/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/COMMD2","classification":"Not Classified","n_dependent_lines":39,"n_total_lines":1208,"dependency_fraction":0.03228476821192053},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000114744","cell_line_id":"CID000267","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"CCDC22","stoichiometry":10.0},{"gene":"CCDC93","stoichiometry":10.0},{"gene":"COMMD1","stoichiometry":10.0},{"gene":"C16ORF62","stoichiometry":10.0},{"gene":"FAM45A;FAM45B","stoichiometry":10.0},{"gene":"COMMD6","stoichiometry":10.0},{"gene":"SSRP1","stoichiometry":10.0},{"gene":"CWF19L2","stoichiometry":10.0},{"gene":"COMMD9","stoichiometry":10.0},{"gene":"VPS29","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000267","total_profiled":1310},"omim":[{"mim_id":"616699","title":"COMM DOMAIN-CONTAINING PROTEIN 2; COMMD2","url":"https://www.omim.org/entry/616699"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Vesicles","reliability":"Uncertain"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/COMMD2"},"hgnc":{"alias_symbol":["HSPC042"],"prev_symbol":[]},"alphafold":{"accession":"Q86X83","domains":[{"cath_id":"-","chopping":"8-118","consensus_level":"high","plddt":89.6787,"start":8,"end":118},{"cath_id":"-","chopping":"122-168","consensus_level":"medium","plddt":93.6468,"start":122,"end":168},{"cath_id":"-","chopping":"172-199","consensus_level":"medium","plddt":86.6511,"start":172,"end":199}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86X83","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q86X83-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q86X83-F1-predicted_aligned_error_v6.png","plddt_mean":89.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=COMMD2","jax_strain_url":"https://www.jax.org/strain/search?query=COMMD2"},"sequence":{"accession":"Q86X83","fasta_url":"https://rest.uniprot.org/uniprotkb/Q86X83.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q86X83/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q86X83"}},"corpus_meta":[{"pmid":"23637203","id":"PMC_23637203","title":"Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel.","date":"2013","source":"American journal of physiology. Renal physiology","url":"https://pubmed.ncbi.nlm.nih.gov/23637203","citation_count":27,"is_preprint":false},{"pmid":"33428145","id":"PMC_33428145","title":"Identification of Serum Exosomal MicroRNA Expression Profiling in Menopausal Females with Osteoporosis by High-throughput Sequencing.","date":"2021","source":"Current medical science","url":"https://pubmed.ncbi.nlm.nih.gov/33428145","citation_count":24,"is_preprint":false},{"pmid":"36205192","id":"PMC_36205192","title":"Multi-omics analysis of the oncogenic value of copper Metabolism-Related protein COMMD2 in human cancers.","date":"2022","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36205192","citation_count":8,"is_preprint":false},{"pmid":"38575039","id":"PMC_38575039","title":"Identification, diversity, and evolution analysis of Commd gene family in Haliotis discus hannai and immune response to biotic and abiotic stresses.","date":"2024","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38575039","citation_count":2,"is_preprint":false},{"pmid":"41233790","id":"PMC_41233790","title":"Non-Lethal heat shock induces COMMD gene activation and enhances pathogen defense in Procambarus clarkii.","date":"2025","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41233790","citation_count":1,"is_preprint":false},{"pmid":"40957961","id":"PMC_40957961","title":"Identification of shared diagnostic biomarkers and potential co-morbidity mechanisms between primary Sjogren's syndrome and chronic kidney disease.","date":"2025","source":"Clinical rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/40957961","citation_count":0,"is_preprint":false},{"pmid":"41200507","id":"PMC_41200507","title":"Screening and regulatory mechanisms of biomarkers related to neddylation in laryngeal squamous cell carcinoma.","date":"2025","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/41200507","citation_count":0,"is_preprint":false},{"pmid":"41685087","id":"PMC_41685087","title":"Preliminary study of cyto-impedance: Molecular profiling of functional impedance in motility-promoting treatment of normal cells.","date":"2026","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/41685087","citation_count":0,"is_preprint":false},{"pmid":"41605412","id":"PMC_41605412","title":"Integrated miRNA-proteomic profiling identifies chronic vesicle-trafficking and proteostasis disruptions after mild traumatic brain injury.","date":"2026","source":"Experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/41605412","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6924,"output_tokens":568,"usd":0.014646,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6907,"output_tokens":1021,"usd":0.03003,"stage2_stop_reason":"end_turn"},"total_usd":0.044676,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"COMMD2 (along with COMMD3–10) interacts with the epithelial sodium channel (ENaC), as demonstrated by interaction assays; the broader family interaction with ENaC was established, though functional follow-up was focused on COMMD3 and COMMD9.\",\n      \"method\": \"Protein interaction assays (Co-IP/pulldown reported for COMMD2–10 interacting with ENaC)\",\n      \"journal\": \"American journal of physiology. Renal physiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab pulldown/interaction assay; functional characterization was performed only for COMMD3 and COMMD9, not COMMD2 specifically\",\n      \"pmids\": [\"23637203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"RNA interference-mediated knockdown of COMMD2 suppressed proliferation and migration of bladder cancer (BLCA) and uterine corpus endometrial carcinoma (UCEC) cell lines, and GSEA analysis linked COMMD2 co-expression networks to E2F targets, G2-M checkpoint, and mitotic spindle pathways in BLCA.\",\n      \"method\": \"RNA interference (siRNA knockdown), CCK-8 proliferation assay, EdU assay, wound healing assay, transwell migration assay, GSEA\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single-lab loss-of-function with defined cellular phenotype but no direct molecular mechanism or pathway placement beyond correlation; no rescue or epistasis experiment\",\n      \"pmids\": [\"36205192\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"COMMD2 physically interacts with the epithelial sodium channel ENaC (as part of the broader COMMD family), and its loss-of-function suppresses cancer cell proliferation and migration with transcriptomic links to E2F/G2-M checkpoint pathways, but the precise molecular mechanism by which COMMD2 exerts these effects remains undefined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"COMMD2 is a member of the COMMD protein family that has been physically linked to the epithelial sodium channel ENaC, where COMMD2 through COMMD10 were shown to interact with the channel in interaction assays [#0]. In cancer cell models, RNA interference-mediated depletion of COMMD2 suppresses proliferation and migration of bladder and uterine endometrial carcinoma cells, with co-expression analysis connecting COMMD2 to E2F target, G2-M checkpoint, and mitotic spindle gene sets [#1]. Beyond these correlative cellular phenotypes and the family-level ENaC interaction, the precise molecular mechanism of COMMD2 has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Established that COMMD2, as part of the COMMD family, can physically associate with the epithelial sodium channel ENaC, placing it in proximity to ion-channel regulation.\",\n      \"evidence\": \"Co-IP/pulldown interaction assays for COMMD2-10 with ENaC\",\n      \"pmids\": [\"23637203\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Functional follow-up was performed only for COMMD3 and COMMD9, not COMMD2 specifically\", \"No demonstration that COMMD2 alters ENaC activity or trafficking\", \"Interaction is reported at the family level without COMMD2-specific reciprocal validation\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Showed that COMMD2 is required for cancer cell proliferation and migration and is transcriptionally correlated with cell-cycle programs, framing it as a candidate pro-proliferative factor.\",\n      \"evidence\": \"siRNA knockdown with CCK-8, EdU, wound healing and transwell assays plus GSEA in BLCA and UCEC cell lines\",\n      \"pmids\": [\"36205192\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct molecular mechanism linking COMMD2 to E2F/G2-M pathways\", \"No rescue or epistasis experiment to confirm specificity\", \"Pathway associations are correlative co-expression signals, not causal placements\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of COMMD2 and the mechanism connecting its physical interactions to its proliferative phenotype remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No biochemical activity assigned to COMMD2\", \"No defined complex or stable subunit assignment\", \"Mechanism linking ENaC interaction and cancer cell phenotype unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"ENaC\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":2,"faith_total":2,"faith_pct":100.0}}