{"gene":"CACNG6","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2026,"finding":"CACNG6 downregulation inhibits calcium ion influx, which indirectly modulates the MAPK pathway, as demonstrated in a mouse pneumonia model using a nanoparticle drug delivery system (PT@M2).","method":"In vivo mouse model with pharmacological intervention and pathway analysis","journal":"Journal of controlled release","confidence":"Low","confidence_rationale":"Tier 3 — single study, indirect mechanistic inference, no direct reconstitution or mutagenesis of CACNG6","pmids":["41819427"],"is_preprint":false},{"year":2010,"finding":"CACNG6 encodes a protein described as stabilizing the voltage-dependent calcium channel, implicated in calcium ion regulation relevant to airway inflammation and bronchodilation.","method":"Genetic association study with functional annotation of CACNG6 role","journal":"BMC medical genetics","confidence":"Low","confidence_rationale":"Tier 4 — functional claim is a literature annotation, not directly experimentally demonstrated in this paper","pmids":["20860846"],"is_preprint":false}],"current_model":"CACNG6 encodes a voltage-dependent calcium channel gamma subunit that stabilizes the channel complex and regulates calcium ion influx; downregulation of CACNG6 reduces calcium influx and indirectly modulates the MAPK pathway, though direct mechanistic characterization (reconstitution, structure, or in vitro enzymatic assay) remains limited in the available literature."},"narrative":{"teleology":[{"year":2010,"claim":"CACNG6 was annotated as a stabilizing subunit of voltage-dependent calcium channels, linking it to calcium ion regulation in the context of airway physiology — but this claim derived from functional annotation rather than direct experimentation on CACNG6.","evidence":"Genetic association study with functional annotation of CACNG6","pmids":["20860846"],"confidence":"Low","gaps":["No direct experimental demonstration of CACNG6 stabilizing the calcium channel complex was performed in this study","No mutagenesis or reconstitution evidence for CACNG6 function","Relationship to specific calcium channel alpha subunits not characterized"]},{"year":2026,"claim":"Pharmacological downregulation of CACNG6 was shown to reduce calcium influx and indirectly modulate the MAPK pathway, providing the first functional perturbation data linking CACNG6 to calcium signaling in an in vivo disease model.","evidence":"In vivo mouse pneumonia model with nanoparticle drug delivery system and pathway analysis","pmids":["41819427"],"confidence":"Low","gaps":["Single study with indirect inference; no genetic knockout, rescue, or direct CACNG6-specific perturbation was performed","MAPK modulation is inferred indirectly and could reflect secondary effects of reduced calcium influx rather than a direct CACNG6 function","No in vitro electrophysiology or biochemical reconstitution to confirm CACNG6's contribution to channel activity"]},{"year":null,"claim":"The direct molecular function of CACNG6 — including which calcium channel complexes it incorporates into, its biophysical effects on channel gating or trafficking, and whether it modulates AMPA receptor trafficking like related family members — remains uncharacterized by direct experimentation.","evidence":"","pmids":[],"confidence":"Low","gaps":["No electrophysiological reconstitution of CACNG6 with defined calcium channel subunits","No structural data for CACNG6 in a channel complex","No comparison of CACNG6 function to other TARP/gamma subunit family members"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"CACNG6 encodes a voltage-dependent calcium channel gamma subunit that stabilizes the channel complex and participates in regulating calcium ion influx [PMID:20860846]. Downregulation of CACNG6 reduces calcium influx and has been linked to indirect modulation of the MAPK pathway in an in vivo mouse pneumonia model [PMID:41819427]. Direct mechanistic characterization of CACNG6 through reconstitution, mutagenesis, or structural studies is largely uncharacterized."},"prefetch_data":{"uniprot":{"accession":"Q9BXT2","full_name":"Voltage-dependent calcium channel gamma-6 subunit","aliases":["Neuronal voltage-gated calcium channel gamma-6 subunit"],"length_aa":260,"mass_kda":28.1,"function":"Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q9BXT2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CACNG6","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CACNG6","total_profiled":1310},"omim":[{"mim_id":"606900","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-8 SUBUNIT; CACNG8","url":"https://www.omim.org/entry/606900"},{"mim_id":"606899","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-7 SUBUNIT; CACNG7","url":"https://www.omim.org/entry/606899"},{"mim_id":"606898","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-6 SUBUNIT; CACNG6","url":"https://www.omim.org/entry/606898"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli fibrillar center","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"skeletal muscle","ntpm":84.9},{"tissue":"tongue","ntpm":28.0}],"url":"https://www.proteinatlas.org/search/CACNG6"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q8WXS5","domains":[{"cath_id":"1.20.140.150","chopping":"25-43_118-187_201-239","consensus_level":"medium","plddt":84.195,"start":25,"end":239}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXS5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXS5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WXS5-F1-predicted_aligned_error_v6.png","plddt_mean":58.66},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CACNG6","jax_strain_url":"https://www.jax.org/strain/search?query=CACNG6"},"sequence":{"accession":"Q8WXS5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WXS5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WXS5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WXS5"}},"corpus_meta":[{"pmid":"27760167","id":"PMC_27760167","title":"Genomic 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asthma.","date":"2025","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41398767","citation_count":1,"is_preprint":false},{"pmid":"41819427","id":"PMC_41819427","title":"M2 macrophage-mediated tigecycline nanoparticles for combating CRKP pneumonia via antibacterial and immunomodulatory therapy.","date":"2026","source":"Journal of controlled release : official journal of the Controlled Release Society","url":"https://pubmed.ncbi.nlm.nih.gov/41819427","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7980,"output_tokens":430,"usd":0.015195},"stage2":{"model":"claude-opus-4-6","input_tokens":3593,"output_tokens":786,"usd":0.056423},"total_usd":0.071618,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2026,\n      \"finding\": \"CACNG6 downregulation inhibits calcium ion influx, which indirectly modulates the MAPK pathway, as demonstrated in a mouse pneumonia model using a nanoparticle drug delivery system (PT@M2).\",\n      \"method\": \"In vivo mouse model with pharmacological intervention and pathway analysis\",\n      \"journal\": \"Journal of controlled release\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single study, indirect mechanistic inference, no direct reconstitution or mutagenesis of CACNG6\",\n      \"pmids\": [\"41819427\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CACNG6 encodes a protein described as stabilizing the voltage-dependent calcium channel, implicated in calcium ion regulation relevant to airway inflammation and bronchodilation.\",\n      \"method\": \"Genetic association study with functional annotation of CACNG6 role\",\n      \"journal\": \"BMC medical genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 — functional claim is a literature annotation, not directly experimentally demonstrated in this paper\",\n      \"pmids\": [\"20860846\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CACNG6 encodes a voltage-dependent calcium channel gamma subunit that stabilizes the channel complex and regulates calcium ion influx; downregulation of CACNG6 reduces calcium influx and indirectly modulates the MAPK pathway, though direct mechanistic characterization (reconstitution, structure, or in vitro enzymatic assay) remains limited in the available literature.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CACNG6 encodes a voltage-dependent calcium channel gamma subunit that stabilizes the channel complex and participates in regulating calcium ion influx [PMID:20860846]. Downregulation of CACNG6 reduces calcium influx and has been linked to indirect modulation of the MAPK pathway in an in vivo mouse pneumonia model [PMID:41819427]. Direct mechanistic characterization of CACNG6 through reconstitution, mutagenesis, or structural studies is largely uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"CACNG6 was annotated as a stabilizing subunit of voltage-dependent calcium channels, linking it to calcium ion regulation in the context of airway physiology — but this claim derived from functional annotation rather than direct experimentation on CACNG6.\",\n      \"evidence\": \"Genetic association study with functional annotation of CACNG6\",\n      \"pmids\": [\"20860846\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct experimental demonstration of CACNG6 stabilizing the calcium channel complex was performed in this study\",\n        \"No mutagenesis or reconstitution evidence for CACNG6 function\",\n        \"Relationship to specific calcium channel alpha subunits not characterized\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Pharmacological downregulation of CACNG6 was shown to reduce calcium influx and indirectly modulate the MAPK pathway, providing the first functional perturbation data linking CACNG6 to calcium signaling in an in vivo disease model.\",\n      \"evidence\": \"In vivo mouse pneumonia model with nanoparticle drug delivery system and pathway analysis\",\n      \"pmids\": [\"41819427\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single study with indirect inference; no genetic knockout, rescue, or direct CACNG6-specific perturbation was performed\",\n        \"MAPK modulation is inferred indirectly and could reflect secondary effects of reduced calcium influx rather than a direct CACNG6 function\",\n        \"No in vitro electrophysiology or biochemical reconstitution to confirm CACNG6's contribution to channel activity\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of CACNG6 — including which calcium channel complexes it incorporates into, its biophysical effects on channel gating or trafficking, and whether it modulates AMPA receptor trafficking like related family members — remains uncharacterized by direct experimentation.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No electrophysiological reconstitution of CACNG6 with defined calcium channel subunits\",\n        \"No structural data for CACNG6 in a channel complex\",\n        \"No comparison of CACNG6 function to other TARP/gamma subunit family members\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}