{"gene":"CACNG5","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":1999,"finding":"CACNG5 was identified as a novel voltage-dependent Ca2+ channel gamma subunit gene, located on chromosomes 16/17, arising through tandem and chromosome duplication events from CACNG1/CACNG2 ancestors, consistent with membership in the gamma subunit gene family.","method":"Low-stringency genomic sequence analysis of targeted chromosomal regions based on syntenic prediction from known CACNG1 and CACNG2 loci","journal":"Genome research","confidence":"Medium","confidence_rationale":"Tier 2 — genomic identification with evolutionary framework, single study, no functional reconstitution","pmids":["10613843"],"is_preprint":false},{"year":2018,"finding":"CACNG5 was identified as a direct target gene of miR-96; inhibition of miR-96 increased CACNG5 expression, which in turn suppressed p38MAPK pathway activation (reduced p-p38MAPK, c-Fos, iNOS, Bax) and decreased dopaminergic neuron apoptosis in an MPTP mouse model of Parkinson's disease.","method":"miR-96 mimic/inhibitor treatment and CACNG5 overexpression plasmid in MPTP mouse model and SH-SY5Y cells; TUNEL staining, Western blot for MAPK pathway components; target validation implied by luciferase or expression rescue","journal":"Molecular medicine (Cambridge, Mass.)","confidence":"Low","confidence_rationale":"Tier 3 — single lab, functional rescue experiment but no direct binding/luciferase assay described in abstract; no independent replication","pmids":["30486773"],"is_preprint":false}],"current_model":"CACNG5 is a voltage-dependent calcium channel gamma subunit whose genomic origin traces to tandem/chromosomal duplication; it is post-transcriptionally regulated by miR-96, and its expression modulates the p38 MAPK signaling pathway to influence neuronal apoptosis, though detailed mechanistic characterization of its channel-regulatory function remains limited."},"narrative":{"teleology":[{"year":1999,"claim":"Establishing CACNG5 as a bona fide gamma subunit family member resolved the question of how many gamma subunit genes exist and how they arose, showing tandem and chromosomal duplication from CACNG1/CACNG2 ancestors.","evidence":"Low-stringency genomic sequence analysis and syntenic mapping across human chromosomes 16/17","pmids":["10613843"],"confidence":"Medium","gaps":["No electrophysiological reconstitution to demonstrate channel-modulatory activity","Expression pattern across tissues not characterized in this study","No protein-level validation of CACNG5 product"]},{"year":2018,"claim":"Linking CACNG5 to the p38 MAPK/apoptosis axis provided the first functional readout for this gene, showing that its upregulation (via miR-96 inhibition) suppresses dopaminergic neuron death in a Parkinson's disease model.","evidence":"miR-96 mimic/inhibitor and CACNG5 overexpression in MPTP mouse model and SH-SY5Y cells; Western blot for p-p38MAPK, c-Fos, iNOS, Bax; TUNEL staining","pmids":["30486773"],"confidence":"Low","gaps":["No direct luciferase reporter assay described to confirm miR-96 binding to CACNG5 3′UTR","Single-lab finding with no independent replication","Mechanism linking a calcium channel subunit to p38 MAPK suppression is unexplained"]},{"year":null,"claim":"Whether CACNG5 modulates voltage-dependent calcium channel gating, trafficking, or surface expression — the canonical function expected of gamma subunits — has never been directly tested.","evidence":"","pmids":[],"confidence":"Low","gaps":["No electrophysiological characterization of CACNG5 effects on calcium currents","No structural or biochemical data on CACNG5 integration into channel complexes","Relationship between channel-modulatory role and MAPK-pathway effects is unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1]}],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"CACNG5 is a member of the voltage-dependent calcium channel gamma subunit family, identified through genomic sequence analysis as arising from tandem and chromosomal duplication of ancestral CACNG1/CACNG2 loci on chromosomes 16 and 17 [PMID:10613843]. Overexpression of CACNG5 suppresses p38 MAPK pathway activation and reduces dopaminergic neuron apoptosis in an MPTP mouse model, and CACNG5 expression is negatively regulated by miR-96 [PMID:30486773]. Detailed mechanistic characterization of its calcium channel-regulatory function remains lacking."},"prefetch_data":{"uniprot":{"accession":"Q9UF02","full_name":"Voltage-dependent calcium channel gamma-5 subunit","aliases":["Neuronal voltage-gated calcium channel gamma-5 subunit","Transmembrane AMPAR regulatory protein gamma-5","TARP gamma-5"],"length_aa":275,"mass_kda":30.9,"function":"Regulates the gating properties of AMPA-selective glutamate receptors (AMPARs). Modulates their gating properties by accelerating their rates of activation, deactivation and desensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity for GRIA1, GRIA4 and the long isoform of GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity)","subcellular_location":"Membrane; Postsynaptic density membrane","url":"https://www.uniprot.org/uniprotkb/Q9UF02/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CACNG5","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CACNG5","total_profiled":1310},"omim":[{"mim_id":"606899","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-7 SUBUNIT; CACNG7","url":"https://www.omim.org/entry/606899"},{"mim_id":"606405","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-5 SUBUNIT; CACNG5","url":"https://www.omim.org/entry/606405"},{"mim_id":"606404","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-4 SUBUNIT; CACNG4","url":"https://www.omim.org/entry/606404"},{"mim_id":"606403","title":"CALCIUM CHANNEL, VOLTAGE-DEPENDENT, GAMMA-3 SUBUNIT; CACNG3","url":"https://www.omim.org/entry/606403"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"retina","ntpm":14.6}],"url":"https://www.proteinatlas.org/search/CACNG5"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9UF02","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UF02","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UF02-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UF02-F1-predicted_aligned_error_v6.png","plddt_mean":73.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CACNG5","jax_strain_url":"https://www.jax.org/strain/search?query=CACNG5"},"sequence":{"accession":"Q9UF02","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UF02.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UF02/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UF02"}},"corpus_meta":[{"pmid":"10613843","id":"PMC_10613843","title":"Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.","date":"1999","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/10613843","citation_count":55,"is_preprint":false},{"pmid":"27102562","id":"PMC_27102562","title":"Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27102562","citation_count":54,"is_preprint":false},{"pmid":"30486773","id":"PMC_30486773","title":"Suppressed microRNA-96 inhibits iNOS expression and dopaminergic neuron apoptosis through inactivating the MAPK signaling pathway by targeting CACNG5 in mice with Parkinson's disease.","date":"2018","source":"Molecular medicine (Cambridge, Mass.)","url":"https://pubmed.ncbi.nlm.nih.gov/30486773","citation_count":32,"is_preprint":false},{"pmid":"31213979","id":"PMC_31213979","title":"Proestrus Differentially Regulates Expression of Ion Channel and Calcium Homeostasis Genes in GnRH Neurons of Mice.","date":"2019","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31213979","citation_count":20,"is_preprint":false},{"pmid":"29215699","id":"PMC_29215699","title":"LncRNA LINC00880 promotes cell proliferation, migration, and invasion while inhibiting apoptosis by targeting CACNG5 through the MAPK signaling pathway in spinal cord ependymoma.","date":"2018","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/29215699","citation_count":8,"is_preprint":false},{"pmid":"31375088","id":"PMC_31375088","title":"Exploring the molecular basis of neuronal excitability in a vocal learner.","date":"2019","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/31375088","citation_count":8,"is_preprint":false},{"pmid":"38615700","id":"PMC_38615700","title":"Study on analgesic effect of Shentong Zhuyu Decoction in neuropathic pain rats by network pharmacology and RNA-Seq.","date":"2024","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/38615700","citation_count":6,"is_preprint":false},{"pmid":"34287864","id":"PMC_34287864","title":"Retraction.","date":"2021","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/34287864","citation_count":0,"is_preprint":false},{"pmid":"37000665","id":"PMC_37000665","title":"[Changes in Expression of Genes Associated with Calcium Processes in the Hippocampus in Mice Exposed to Chronic Social Stress].","date":"2023","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/37000665","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6514,"output_tokens":578,"usd":0.014106},"stage2":{"model":"claude-opus-4-6","input_tokens":3741,"output_tokens":862,"usd":0.060382},"total_usd":0.074488,"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\": 1999,\n      \"finding\": \"CACNG5 was identified as a novel voltage-dependent Ca2+ channel gamma subunit gene, located on chromosomes 16/17, arising through tandem and chromosome duplication events from CACNG1/CACNG2 ancestors, consistent with membership in the gamma subunit gene family.\",\n      \"method\": \"Low-stringency genomic sequence analysis of targeted chromosomal regions based on syntenic prediction from known CACNG1 and CACNG2 loci\",\n      \"journal\": \"Genome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genomic identification with evolutionary framework, single study, no functional reconstitution\",\n      \"pmids\": [\"10613843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CACNG5 was identified as a direct target gene of miR-96; inhibition of miR-96 increased CACNG5 expression, which in turn suppressed p38MAPK pathway activation (reduced p-p38MAPK, c-Fos, iNOS, Bax) and decreased dopaminergic neuron apoptosis in an MPTP mouse model of Parkinson's disease.\",\n      \"method\": \"miR-96 mimic/inhibitor treatment and CACNG5 overexpression plasmid in MPTP mouse model and SH-SY5Y cells; TUNEL staining, Western blot for MAPK pathway components; target validation implied by luciferase or expression rescue\",\n      \"journal\": \"Molecular medicine (Cambridge, Mass.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, functional rescue experiment but no direct binding/luciferase assay described in abstract; no independent replication\",\n      \"pmids\": [\"30486773\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CACNG5 is a voltage-dependent calcium channel gamma subunit whose genomic origin traces to tandem/chromosomal duplication; it is post-transcriptionally regulated by miR-96, and its expression modulates the p38 MAPK signaling pathway to influence neuronal apoptosis, though detailed mechanistic characterization of its channel-regulatory function remains limited.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CACNG5 is a member of the voltage-dependent calcium channel gamma subunit family, identified through genomic sequence analysis as arising from tandem and chromosomal duplication of ancestral CACNG1/CACNG2 loci on chromosomes 16 and 17 [PMID:10613843]. Overexpression of CACNG5 suppresses p38 MAPK pathway activation and reduces dopaminergic neuron apoptosis in an MPTP mouse model, and CACNG5 expression is negatively regulated by miR-96 [PMID:30486773]. Detailed mechanistic characterization of its calcium channel-regulatory function remains lacking.\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Establishing CACNG5 as a bona fide gamma subunit family member resolved the question of how many gamma subunit genes exist and how they arose, showing tandem and chromosomal duplication from CACNG1/CACNG2 ancestors.\",\n      \"evidence\": \"Low-stringency genomic sequence analysis and syntenic mapping across human chromosomes 16/17\",\n      \"pmids\": [\"10613843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No electrophysiological reconstitution to demonstrate channel-modulatory activity\",\n        \"Expression pattern across tissues not characterized in this study\",\n        \"No protein-level validation of CACNG5 product\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Linking CACNG5 to the p38 MAPK/apoptosis axis provided the first functional readout for this gene, showing that its upregulation (via miR-96 inhibition) suppresses dopaminergic neuron death in a Parkinson's disease model.\",\n      \"evidence\": \"miR-96 mimic/inhibitor and CACNG5 overexpression in MPTP mouse model and SH-SY5Y cells; Western blot for p-p38MAPK, c-Fos, iNOS, Bax; TUNEL staining\",\n      \"pmids\": [\"30486773\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct luciferase reporter assay described to confirm miR-96 binding to CACNG5 3′UTR\",\n        \"Single-lab finding with no independent replication\",\n        \"Mechanism linking a calcium channel subunit to p38 MAPK suppression is unexplained\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether CACNG5 modulates voltage-dependent calcium channel gating, trafficking, or surface expression — the canonical function expected of gamma subunits — has never been directly tested.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No electrophysiological characterization of CACNG5 effects on calcium currents\",\n        \"No structural or biochemical data on CACNG5 integration into channel complexes\",\n        \"Relationship between channel-modulatory role and MAPK-pathway effects is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"R-HSA-162582\",\n        \"supporting_discovery_ids\": [1]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}