{"gene":"CAV2","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2018,"finding":"CAV2 (Caveolin-2) knockdown in renal cell carcinoma OS-RC-2 cells inhibited proliferation, migration, and invasion, and reduced expression of EGFR, PI3K, and phospho-Akt, placing CAV2 upstream of the EGFR/PI3K/Akt signaling pathway in kidney cancer cells.","method":"siRNA knockdown combined with wound healing, Matrigel invasion assays, Western blotting, and mouse orthotopic xenograft model","journal":"OncoTargets and therapy","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single knockdown approach with pathway readout by Western blot; no direct binding or reconstitution assay establishing mechanistic link","pmids":["30288056"],"is_preprint":false},{"year":2022,"finding":"CAV2 (Caveolin-2) overexpression in pancreatic cancer cells activates the Wnt7A/β-catenin signaling pathway and promotes invasion, migration, and metastasis; CAV2 regulates this axis by inhibiting endocytosis and promoting epithelial-mesenchymal transition (EMT). MiR-4723 negatively regulates CAV2 expression, and CAV2 in turn modulates the MiR-4723/Wnt7A signaling axis.","method":"Overexpression and knockdown experiments, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter assay, cell proliferation/invasion/migration assays","journal":"Journal of Cancer","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, multiple cellular assays but no direct binding/reconstitution experiments establishing mechanism; pathway placement inferred from expression changes after overexpression","pmids":["35517414"],"is_preprint":false}],"current_model":"Caveolin-2 (CAV2) has been experimentally linked to promotion of cancer cell proliferation, migration, and invasion through the EGFR/PI3K/Akt pathway in renal cell carcinoma and through activation of the Wnt7A/β-catenin pathway (regulated by a MiR-4723/Wnt7A axis) in pancreatic cancer, with roles in modulating endocytosis and epithelial-mesenchymal transition; however, these findings rest on single-lab studies with limited mechanistic depth, and no structural, biochemical reconstitution, or direct binding data for CAV2 protein function appear in the available literature."},"narrative":{"mechanistic_narrative":"Caveolin-2 (CAV2) has been linked to the promotion of cancer cell proliferation, migration, and invasion in two tumor contexts, though its molecular function remains uncharacterized in the available corpus. In renal cell carcinoma cells, CAV2 acts upstream of EGFR/PI3K/Akt signaling: its knockdown reduces EGFR, PI3K, and phospho-Akt levels and suppresses proliferation, migration, and invasion [PMID:30288056]. In pancreatic cancer cells, CAV2 overexpression activates Wnt7A/β-catenin signaling and drives invasion and metastasis by inhibiting endocytosis and promoting epithelial-mesenchymal transition, with CAV2 expression negatively regulated by MiR-4723 within a MiR-4723/Wnt7A axis [PMID:35517414]. Beyond these phenotypic associations, no direct binding, structural, or biochemical reconstitution data establish CAV2's molecular mechanism in the available corpus.","teleology":[{"year":2018,"claim":"Established a pro-tumorigenic role for CAV2 in renal cell carcinoma by placing it upstream of a defined oncogenic signaling pathway.","evidence":"siRNA knockdown with wound healing, Matrigel invasion, Western blotting, and orthotopic xenograft in OS-RC-2 cells","pmids":["30288056"],"confidence":"Low","gaps":["Single lab, knockdown-only with Western blot pathway readout; no direct binding or reconstitution establishing the mechanistic link to EGFR/PI3K/Akt","Whether CAV2 physically interacts with EGFR or pathway components is not shown","No structural or biochemical characterization of CAV2 activity"]},{"year":2022,"claim":"Extended CAV2's oncogenic role to pancreatic cancer and connected it to Wnt7A/β-catenin signaling, EMT, and upstream microRNA regulation.","evidence":"Overexpression/knockdown, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter, and proliferation/invasion/migration assays in pancreatic cancer cells","pmids":["35517414"],"confidence":"Low","gaps":["Single lab; pathway placement inferred from expression changes after overexpression without direct binding/reconstitution","Mechanism by which CAV2 inhibits endocytosis to modulate signaling is not defined","Direct MiR-4723/CAV2 targeting versus indirect regulation not fully resolved"]},{"year":null,"claim":"The molecular activity, structure, and direct binding partners of CAV2 protein remain undefined.","evidence":"No reconstitution, structural, or direct interaction data in the available corpus","pmids":[],"confidence":"Low","gaps":["No direct biochemical or structural characterization of CAV2","No validated physical interaction partners","Mechanism connecting CAV2 to EGFR/PI3K/Akt and Wnt7A/β-catenin pathways not established"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P51636","full_name":"Caveolin-2","aliases":[],"length_aa":162,"mass_kda":18.3,"function":"May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity)","subcellular_location":"Nucleus; Cytoplasm; Golgi apparatus membrane; Cell membrane; Membrane, caveola","url":"https://www.uniprot.org/uniprotkb/P51636/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CAV2","classification":"Not Classified","n_dependent_lines":8,"n_total_lines":1208,"dependency_fraction":0.006622516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CAV2","total_profiled":1310},"omim":[{"mim_id":"620144","title":"CACHE DOMAIN-CONTAINING PROTEIN 1; CACHD1","url":"https://www.omim.org/entry/620144"},{"mim_id":"619863","title":"JUNCTOPHILIN 4; JPH4","url":"https://www.omim.org/entry/619863"},{"mim_id":"618497","title":"NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND NONEPILEPTIC HYPERKINETIC MOVEMENTS; NEDNEH","url":"https://www.omim.org/entry/618497"},{"mim_id":"615200","title":"PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN, FAMILY F, MEMBER 1; PLEKHF1","url":"https://www.omim.org/entry/615200"},{"mim_id":"610388","title":"RRAD- AND GEM-LIKE GTPase 1; REM1","url":"https://www.omim.org/entry/610388"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"adipose tissue","ntpm":213.4}],"url":"https://www.proteinatlas.org/search/CAV2"},"hgnc":{"alias_symbol":["CAV"],"prev_symbol":[]},"alphafold":{"accession":"P51636","domains":[{"cath_id":"1.20.5","chopping":"65-146","consensus_level":"medium","plddt":91.5656,"start":65,"end":146}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P51636","model_url":"https://alphafold.ebi.ac.uk/files/AF-P51636-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P51636-F1-predicted_aligned_error_v6.png","plddt_mean":78.38},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CAV2","jax_strain_url":"https://www.jax.org/strain/search?query=CAV2"},"sequence":{"accession":"P51636","fasta_url":"https://rest.uniprot.org/uniprotkb/P51636.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P51636/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P51636"}},"corpus_meta":[{"pmid":"20668236","id":"PMC_20668236","title":"Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain.","date":"2010","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/20668236","citation_count":250,"is_preprint":false},{"pmid":"17132857","id":"PMC_17132857","title":"Direct G protein modulation of Cav2 calcium channels.","date":"2006","source":"Pharmacological reviews","url":"https://pubmed.ncbi.nlm.nih.gov/17132857","citation_count":184,"is_preprint":false},{"pmid":"20204399","id":"PMC_20204399","title":"CaV2.1 channelopathies.","date":"2010","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/20204399","citation_count":175,"is_preprint":false},{"pmid":"23063655","id":"PMC_23063655","title":"Regulation of Ca(V)2 calcium channels by G protein coupled receptors.","date":"2012","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23063655","citation_count":152,"is_preprint":false},{"pmid":"19249276","id":"PMC_19249276","title":"A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels.","date":"2009","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/19249276","citation_count":140,"is_preprint":false},{"pmid":"10791962","id":"PMC_10791962","title":"CaV2.2 and CaV2.3 (N- and R-type) Ca2+ channels in depolarization-evoked entry of Ca2+ into mouse sperm.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10791962","citation_count":138,"is_preprint":false},{"pmid":"19903690","id":"PMC_19903690","title":"Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons.","date":"2009","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/19903690","citation_count":126,"is_preprint":false},{"pmid":"15743764","id":"PMC_15743764","title":"Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15743764","citation_count":112,"is_preprint":false},{"pmid":"21389219","id":"PMC_21389219","title":"Calcitonin gene-related peptide-mediated enhancement of purinergic neuron/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2.1 Knock-in mice: implications for basic mechanisms of migraine pain.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21389219","citation_count":108,"is_preprint":false},{"pmid":"14660672","id":"PMC_14660672","title":"Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14660672","citation_count":108,"is_preprint":false},{"pmid":"21233207","id":"PMC_21233207","title":"Beta-subunits promote the expression of Ca(V)2.2 channels by reducing their proteasomal degradation.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21233207","citation_count":105,"is_preprint":false},{"pmid":"11214675","id":"PMC_11214675","title":"Detection and differentiation of CAV-1 and CAV-2 by polymerase chain reaction.","date":"2001","source":"Veterinary research communications","url":"https://pubmed.ncbi.nlm.nih.gov/11214675","citation_count":101,"is_preprint":false},{"pmid":"14966867","id":"PMC_14966867","title":"Electrophysiological and molecular evidence of L-(Cav1), N- (Cav2.2), and R- (Cav2.3) type Ca2+ channels in rat cortical astrocytes.","date":"2004","source":"Glia","url":"https://pubmed.ncbi.nlm.nih.gov/14966867","citation_count":78,"is_preprint":false},{"pmid":"16049183","id":"PMC_16049183","title":"Modulation of CaV2.1 channels by the neuronal calcium-binding protein visinin-like protein-2.","date":"2005","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/16049183","citation_count":77,"is_preprint":false},{"pmid":"11606638","id":"PMC_11606638","title":"Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs.","date":"2001","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/11606638","citation_count":75,"is_preprint":false},{"pmid":"23380425","id":"PMC_23380425","title":"Mechanisms of conotoxin inhibition of N-type (Ca(v)2.2) calcium channels.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/23380425","citation_count":73,"is_preprint":false},{"pmid":"15953418","id":"PMC_15953418","title":"G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels.","date":"2005","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/15953418","citation_count":72,"is_preprint":false},{"pmid":"25782368","id":"PMC_25782368","title":"A membrane-delimited N-myristoylated CRMP2 peptide aptamer inhibits CaV2.2 trafficking and reverses inflammatory and postoperative pain behaviors.","date":"2015","source":"Pain","url":"https://pubmed.ncbi.nlm.nih.gov/25782368","citation_count":71,"is_preprint":false},{"pmid":"21150298","id":"PMC_21150298","title":"G protein modulation of CaV2 voltage-gated calcium channels.","date":"2010","source":"Channels (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21150298","citation_count":70,"is_preprint":false},{"pmid":"19718034","id":"PMC_19718034","title":"Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha(2)delta subunit UNC-36.","date":"2009","source":"Nature neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/19718034","citation_count":70,"is_preprint":false},{"pmid":"15950195","id":"PMC_15950195","title":"Use-dependent blockade of Cav2.2 voltage-gated calcium channels for neuropathic pain.","date":"2005","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15950195","citation_count":70,"is_preprint":false},{"pmid":"31704946","id":"PMC_31704946","title":"Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson's disease.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31704946","citation_count":69,"is_preprint":false},{"pmid":"11927536","id":"PMC_11927536","title":"The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression.","date":"2002","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/11927536","citation_count":67,"is_preprint":false},{"pmid":"12704197","id":"PMC_12704197","title":"Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca2+ channel.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12704197","citation_count":65,"is_preprint":false},{"pmid":"22279216","id":"PMC_22279216","title":"Cav2.1 in cerebellar Purkinje cells regulates competitive excitatory synaptic wiring, cell survival, and cerebellar biochemical compartmentalization.","date":"2012","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22279216","citation_count":64,"is_preprint":false},{"pmid":"16857708","id":"PMC_16857708","title":"Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels.","date":"2006","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16857708","citation_count":64,"is_preprint":false},{"pmid":"30104341","id":"PMC_30104341","title":"α-Neurexins Together with α2δ-1 Auxiliary Subunits Regulate Ca2+ Influx through Cav2.1 Channels.","date":"2018","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/30104341","citation_count":63,"is_preprint":false},{"pmid":"11403683","id":"PMC_11403683","title":"The Cav2.1/alpha1A (P/Q-type) voltage-dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells.","date":"2001","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/11403683","citation_count":60,"is_preprint":false},{"pmid":"15607937","id":"PMC_15607937","title":"Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site.","date":"2005","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/15607937","citation_count":58,"is_preprint":false},{"pmid":"24525187","id":"PMC_24525187","title":"Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization.","date":"2014","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/24525187","citation_count":57,"is_preprint":false},{"pmid":"29879392","id":"PMC_29879392","title":"A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons.","date":"2018","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/29879392","citation_count":56,"is_preprint":false},{"pmid":"26283199","id":"PMC_26283199","title":"Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.","date":"2015","source":"The Journal of general physiology","url":"https://pubmed.ncbi.nlm.nih.gov/26283199","citation_count":55,"is_preprint":false},{"pmid":"16049184","id":"PMC_16049184","title":"Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation.","date":"2005","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/16049184","citation_count":53,"is_preprint":false},{"pmid":"29198756","id":"PMC_29198756","title":"CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian Sensory Neurons.","date":"2017","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/29198756","citation_count":49,"is_preprint":false},{"pmid":"22613715","id":"PMC_22613715","title":"γ-Aminobutyric acid type B (GABAB) receptor expression is needed for inhibition of N-type (Cav2.2) calcium channels by analgesic α-conotoxins.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22613715","citation_count":46,"is_preprint":false},{"pmid":"20194127","id":"PMC_20194127","title":"Insights into migraine mechanisms and CaV2.1 calcium channel function from mouse models of familial hemiplegic migraine.","date":"2010","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/20194127","citation_count":45,"is_preprint":false},{"pmid":"17125805","id":"PMC_17125805","title":"Roscovitine differentially affects CaV2 and Kv channels by binding to the open state.","date":"2006","source":"Neuropharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/17125805","citation_count":45,"is_preprint":false},{"pmid":"17265461","id":"PMC_17265461","title":"Ca(v)1.2, Ca(v)1.3, and Ca(v)2.1 in the mouse hippocampus during and after pilocarpine-induced status epilepticus.","date":"2007","source":"Hippocampus","url":"https://pubmed.ncbi.nlm.nih.gov/17265461","citation_count":44,"is_preprint":false},{"pmid":"19903821","id":"PMC_19903821","title":"N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19903821","citation_count":43,"is_preprint":false},{"pmid":"17145762","id":"PMC_17145762","title":"Molecular basis of Ca(v)2.3 calcium channels in rat nociceptive neurons.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17145762","citation_count":41,"is_preprint":false},{"pmid":"21870131","id":"PMC_21870131","title":"Purkinje cell-specific ablation of Cav2.1 channels is sufficient to cause cerebellar ataxia in mice.","date":"2012","source":"Cerebellum (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/21870131","citation_count":40,"is_preprint":false},{"pmid":"24688019","id":"PMC_24688019","title":"Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and α-conotoxin Vc1.1 via GABAB receptor activation.","date":"2014","source":"The Journal of general physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24688019","citation_count":37,"is_preprint":false},{"pmid":"14505496","id":"PMC_14505496","title":"Human neuronal stargazin-like proteins, gamma2, gamma3 and gamma4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes.","date":"2003","source":"BMC neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/14505496","citation_count":37,"is_preprint":false},{"pmid":"30983967","id":"PMC_30983967","title":"CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems.","date":"2019","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/30983967","citation_count":36,"is_preprint":false},{"pmid":"21150296","id":"PMC_21150296","title":"The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels.","date":"2010","source":"Channels (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21150296","citation_count":36,"is_preprint":false},{"pmid":"30288056","id":"PMC_30288056","title":"CAV2 promotes the growth of renal cell carcinoma through the EGFR/PI3K/Akt pathway.","date":"2018","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/30288056","citation_count":34,"is_preprint":false},{"pmid":"15630435","id":"PMC_15630435","title":"CaV2.3 channel and PKClambda: new players in insulin secretion.","date":"2005","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/15630435","citation_count":34,"is_preprint":false},{"pmid":"31607850","id":"PMC_31607850","title":"Inflammation Induced Sensory Nerve Growth and Pain Hypersensitivity Requires the N-Type Calcium Channel Cav2.2.","date":"2019","source":"Frontiers in neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31607850","citation_count":33,"is_preprint":false},{"pmid":"18923037","id":"PMC_18923037","title":"The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2.","date":"2008","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/18923037","citation_count":33,"is_preprint":false},{"pmid":"23817128","id":"PMC_23817128","title":"Protein kinase Cα and P-type Ca channel CaV2.1 in red blood cell calcium signalling.","date":"2013","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/23817128","citation_count":32,"is_preprint":false},{"pmid":"30946560","id":"PMC_30946560","title":"Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Physalin F via Block of CaV2.3 (R-Type) and CaV2.2 (N-Type) Voltage-Gated Calcium Channels.","date":"2019","source":"ACS chemical neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/30946560","citation_count":32,"is_preprint":false},{"pmid":"19446536","id":"PMC_19446536","title":"Motor coordination impairment in aged heterozygous rolling Nagoya, Cav2.1 mutant mice.","date":"2009","source":"Brain research","url":"https://pubmed.ncbi.nlm.nih.gov/19446536","citation_count":32,"is_preprint":false},{"pmid":"12771191","id":"PMC_12771191","title":"Custom distinctions in the interaction of G-protein beta subunits with N-type (CaV2.2) versus P/Q-type (CaV2.1) calcium channels.","date":"2003","source":"The Journal of general physiology","url":"https://pubmed.ncbi.nlm.nih.gov/12771191","citation_count":30,"is_preprint":false},{"pmid":"23831344","id":"PMC_23831344","title":"Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides.","date":"2013","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/23831344","citation_count":30,"is_preprint":false},{"pmid":"28614186","id":"PMC_28614186","title":"miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels.","date":"2017","source":"Pain","url":"https://pubmed.ncbi.nlm.nih.gov/28614186","citation_count":30,"is_preprint":false},{"pmid":"27629721","id":"PMC_27629721","title":"Spinal Fbxo3-Dependent Fbxl2 Ubiquitination of Active Zone Protein RIM1α Mediates Neuropathic Allodynia through CaV2.2 Activation.","date":"2016","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/27629721","citation_count":30,"is_preprint":false},{"pmid":"37972067","id":"PMC_37972067","title":"A peptidomimetic modulator of the CaV2.2 N-type calcium channel for chronic pain.","date":"2023","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/37972067","citation_count":29,"is_preprint":false},{"pmid":"35043234","id":"PMC_35043234","title":"Voltage-dependent CaV3.2 and CaV2.2 channels in nociceptive pathways.","date":"2022","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/35043234","citation_count":28,"is_preprint":false},{"pmid":"24394417","id":"PMC_24394417","title":"Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24394417","citation_count":27,"is_preprint":false},{"pmid":"15548655","id":"PMC_15548655","title":"Presynaptic Cav2.1 and Cav2.2 differentially influence release dynamics at hippocampal excitatory synapses.","date":"2004","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/15548655","citation_count":27,"is_preprint":false},{"pmid":"23255606","id":"PMC_23255606","title":"Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2.1 calcium channels.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23255606","citation_count":27,"is_preprint":false},{"pmid":"14507926","id":"PMC_14507926","title":"Competitive and synergistic interactions of G protein beta(2) and Ca(2+) channel beta(1b) subunits with Ca(v)2.1 channels, revealed by mammalian two-hybrid and fluorescence resonance energy transfer measurements.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14507926","citation_count":27,"is_preprint":false},{"pmid":"36820519","id":"PMC_36820519","title":"CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/36820519","citation_count":26,"is_preprint":false},{"pmid":"14742680","id":"PMC_14742680","title":"Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors.","date":"2004","source":"Molecular pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/14742680","citation_count":26,"is_preprint":false},{"pmid":"25225550","id":"PMC_25225550","title":"Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit.","date":"2014","source":"The Journal of general physiology","url":"https://pubmed.ncbi.nlm.nih.gov/25225550","citation_count":26,"is_preprint":false},{"pmid":"18001290","id":"PMC_18001290","title":"Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current.","date":"2007","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/18001290","citation_count":25,"is_preprint":false},{"pmid":"15548431","id":"PMC_15548431","title":"A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner.","date":"2004","source":"Brain research. Molecular brain research","url":"https://pubmed.ncbi.nlm.nih.gov/15548431","citation_count":25,"is_preprint":false},{"pmid":"26015768","id":"PMC_26015768","title":"Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk.","date":"2015","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/26015768","citation_count":24,"is_preprint":false},{"pmid":"36137995","id":"PMC_36137995","title":"Cav2.2-NFAT2-USP43 axis promotes invadopodia formation and breast cancer metastasis through cortactin stabilization.","date":"2022","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/36137995","citation_count":24,"is_preprint":false},{"pmid":"21550405","id":"PMC_21550405","title":"Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6.","date":"2011","source":"Neurobiology of disease","url":"https://pubmed.ncbi.nlm.nih.gov/21550405","citation_count":24,"is_preprint":false},{"pmid":"18797193","id":"PMC_18797193","title":"Functional properties and modulation of extracellular epitope-tagged Ca(V)2.1 voltage-gated calcium channels.","date":"2008","source":"Channels (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/18797193","citation_count":24,"is_preprint":false},{"pmid":"24639630","id":"PMC_24639630","title":"Synaptic vesicle tethering and the CaV2.2 distal C-terminal.","date":"2014","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24639630","citation_count":23,"is_preprint":false},{"pmid":"24790266","id":"PMC_24790266","title":"The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.","date":"2014","source":"Sleep","url":"https://pubmed.ncbi.nlm.nih.gov/24790266","citation_count":23,"is_preprint":false},{"pmid":"33769283","id":"PMC_33769283","title":"Neuronal junctophilins recruit specific CaV and RyR isoforms to ER-PM junctions and functionally alter CaV2.1 and CaV2.2.","date":"2021","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/33769283","citation_count":23,"is_preprint":false},{"pmid":"24566975","id":"PMC_24566975","title":"CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination and degradation.","date":"2014","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24566975","citation_count":23,"is_preprint":false},{"pmid":"38081835","id":"PMC_38081835","title":"Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38081835","citation_count":22,"is_preprint":false},{"pmid":"33913808","id":"PMC_33913808","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals.","date":"2021","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/33913808","citation_count":21,"is_preprint":false},{"pmid":"24755485","id":"PMC_24755485","title":"N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice.","date":"2014","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/24755485","citation_count":21,"is_preprint":false},{"pmid":"19170253","id":"PMC_19170253","title":"Munc18: a presynaptic transmitter release site N type (CaV2.2) calcium channel interacting protein.","date":"2007","source":"Channels (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/19170253","citation_count":20,"is_preprint":false},{"pmid":"33413531","id":"PMC_33413531","title":"A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels.","date":"2021","source":"Molecular brain","url":"https://pubmed.ncbi.nlm.nih.gov/33413531","citation_count":20,"is_preprint":false},{"pmid":"35655070","id":"PMC_35655070","title":"Complex effects on CaV2.1 channel gating caused by a CACNA1A variant associated with a severe neurodevelopmental disorder.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35655070","citation_count":19,"is_preprint":false},{"pmid":"31808667","id":"PMC_31808667","title":"Dopamine Receptor Type 2 and Ghrelin Receptor Coexpression Alters CaV2.2 Modulation by G Protein Signaling Cascades.","date":"2019","source":"ACS chemical neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31808667","citation_count":18,"is_preprint":false},{"pmid":"21521766","id":"PMC_21521766","title":"Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca²+ channel peptides.","date":"2011","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/21521766","citation_count":18,"is_preprint":false},{"pmid":"24523520","id":"PMC_24523520","title":"Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics.","date":"2014","source":"Journal of neurophysiology","url":"https://pubmed.ncbi.nlm.nih.gov/24523520","citation_count":18,"is_preprint":false},{"pmid":"35050960","id":"PMC_35050960","title":"Conotoxin contulakin-G engages a neurotensin receptor 2/R-type calcium channel (Cav2.3) pathway to mediate spinal antinociception.","date":"2021","source":"Pain","url":"https://pubmed.ncbi.nlm.nih.gov/35050960","citation_count":17,"is_preprint":false},{"pmid":"23648579","id":"PMC_23648579","title":"Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels.","date":"2013","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/23648579","citation_count":17,"is_preprint":false},{"pmid":"20511524","id":"PMC_20511524","title":"G-proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage-dependent regulation of mammalian Cav2.1 and Cav2.2 channels.","date":"2010","source":"The Journal of experimental biology","url":"https://pubmed.ncbi.nlm.nih.gov/20511524","citation_count":17,"is_preprint":false},{"pmid":"19811616","id":"PMC_19811616","title":"Nuclear localization of Ca(v)2.2 and its distribution in the mouse central nervous system, and changes in the hippocampus during and after pilocarpine-induced status epilepticus.","date":"2009","source":"Neuropathology and applied neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/19811616","citation_count":17,"is_preprint":false},{"pmid":"39656529","id":"PMC_39656529","title":"C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models.","date":"2024","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/39656529","citation_count":16,"is_preprint":false},{"pmid":"32529299","id":"PMC_32529299","title":"Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective.","date":"2020","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/32529299","citation_count":16,"is_preprint":false},{"pmid":"31350260","id":"PMC_31350260","title":"Disruption of GpI mGluR-Dependent Cav2.3 Translation in a Mouse Model of Fragile X Syndrome.","date":"2019","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/31350260","citation_count":16,"is_preprint":false},{"pmid":"32116539","id":"PMC_32116539","title":"Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies.","date":"2020","source":"Frontiers in molecular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/32116539","citation_count":16,"is_preprint":false},{"pmid":"36970201","id":"PMC_36970201","title":"Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain.","date":"2023","source":"Acta pharmaceutica Sinica. B","url":"https://pubmed.ncbi.nlm.nih.gov/36970201","citation_count":16,"is_preprint":false},{"pmid":"35792082","id":"PMC_35792082","title":"β2-subunit alternative splicing stabilizes Cav2.3 Ca2+ channel activity during continuous midbrain dopamine neuron-like activity.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35792082","citation_count":15,"is_preprint":false},{"pmid":"29111846","id":"PMC_29111846","title":"Investigation of CAV1/CAV2 rs4236601 and CDKN2B-AS1 rs2157719 in primary open-angle glaucoma patients from Brazil.","date":"2017","source":"Ophthalmic genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29111846","citation_count":15,"is_preprint":false},{"pmid":"11976940","id":"PMC_11976940","title":"Kinetics and Gbetagamma modulation of Ca(v)2.2 channels with different auxiliary beta subunits.","date":"2002","source":"Pflugers Archiv : European journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/11976940","citation_count":15,"is_preprint":false},{"pmid":"29067356","id":"PMC_29067356","title":"Cell-Specific RNA Binding Protein Rbfox2 Regulates CaV2.2 mRNA Exon Composition and CaV2.2 Current Size.","date":"2017","source":"eNeuro","url":"https://pubmed.ncbi.nlm.nih.gov/29067356","citation_count":14,"is_preprint":false},{"pmid":"31477143","id":"PMC_31477143","title":"Ankyrin B and Ankyrin B variants differentially modulate intracellular and surface Cav2.1 levels.","date":"2019","source":"Molecular brain","url":"https://pubmed.ncbi.nlm.nih.gov/31477143","citation_count":14,"is_preprint":false},{"pmid":"22074995","id":"PMC_22074995","title":"CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis.","date":"2011","source":"Journal of physiology, Paris","url":"https://pubmed.ncbi.nlm.nih.gov/22074995","citation_count":14,"is_preprint":false},{"pmid":"35517414","id":"PMC_35517414","title":"CAV2 Regulates Mir-4723/Wnt7A Signalling Axis through Endocytosis and Epithelial-Mesenchymal Transition to Promote Proliferation, Invasion, and Metastasis of Pancreatic Cancer Cells.","date":"2022","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/35517414","citation_count":14,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":54886,"output_tokens":1185,"usd":0.091217,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7082,"output_tokens":1245,"usd":0.033267,"stage2_stop_reason":"end_turn"},"total_usd":0.124484,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to identify what \"CAV2\" refers to. The query is for gene CAV2. The corpus contains papers about:\n\n1. **Cav2 voltage-gated calcium channels** (CaV2.1, CaV2.2, CaV2.3) - these are encoded by CACNA1A, CACNA1B, CACNA1E genes\n2. **Caveolin-2 (CAV2)** - papers [46], [68], [95], [100] - this is the actual human gene CAV2 at chromosome 7q31\n3. **Canine adenovirus type 2 (CAV-2)** - papers [12], [31], [44] - viral/vector biology, not the human gene\n\nThe human gene CAV2 encodes **Caveolin-2**, a scaffolding protein in caveolae. Papers [46], [68], [95], [100] are about this gene.\n\nPapers about CaV2 voltage-gated calcium channels are about CACNA1A/B/E genes, NOT the CAV2 gene. These are symbol collisions - the \"Cav2\" family notation refers to a different gene family entirely.\n\nLet me check papers [46] and [100] for mechanistic content:\n\n- **[46]** (PMID 30288056): CAV2 (Caveolin-2) in renal cell carcinoma - silencing CAV2 inhibited proliferation/migration/invasion and reduced EGFR, PI3K, p-Akt expression. This establishes a pathway link via loss-of-function.\n\n- **[100]** (PMID 35517414): CAV2 in pancreatic cancer - overexpression promotes invasion/migration; CAV2 activates Wnt7A/β-catenin; regulates MiR-4723/Wnt7A axis via endocytosis and EMT.\n\nPapers [68] and [95] are GWAS/eQTL association studies - excluded.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"CAV2 (Caveolin-2) knockdown in renal cell carcinoma OS-RC-2 cells inhibited proliferation, migration, and invasion, and reduced expression of EGFR, PI3K, and phospho-Akt, placing CAV2 upstream of the EGFR/PI3K/Akt signaling pathway in kidney cancer cells.\",\n      \"method\": \"siRNA knockdown combined with wound healing, Matrigel invasion assays, Western blotting, and mouse orthotopic xenograft model\",\n      \"journal\": \"OncoTargets and therapy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single knockdown approach with pathway readout by Western blot; no direct binding or reconstitution assay establishing mechanistic link\",\n      \"pmids\": [\"30288056\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CAV2 (Caveolin-2) overexpression in pancreatic cancer cells activates the Wnt7A/β-catenin signaling pathway and promotes invasion, migration, and metastasis; CAV2 regulates this axis by inhibiting endocytosis and promoting epithelial-mesenchymal transition (EMT). MiR-4723 negatively regulates CAV2 expression, and CAV2 in turn modulates the MiR-4723/Wnt7A signaling axis.\",\n      \"method\": \"Overexpression and knockdown experiments, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter assay, cell proliferation/invasion/migration assays\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, multiple cellular assays but no direct binding/reconstitution experiments establishing mechanism; pathway placement inferred from expression changes after overexpression\",\n      \"pmids\": [\"35517414\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Caveolin-2 (CAV2) has been experimentally linked to promotion of cancer cell proliferation, migration, and invasion through the EGFR/PI3K/Akt pathway in renal cell carcinoma and through activation of the Wnt7A/β-catenin pathway (regulated by a MiR-4723/Wnt7A axis) in pancreatic cancer, with roles in modulating endocytosis and epithelial-mesenchymal transition; however, these findings rest on single-lab studies with limited mechanistic depth, and no structural, biochemical reconstitution, or direct binding data for CAV2 protein function appear in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Caveolin-2 (CAV2) has been linked to the promotion of cancer cell proliferation, migration, and invasion in two tumor contexts, though its molecular function remains uncharacterized in the available corpus. In renal cell carcinoma cells, CAV2 acts upstream of EGFR/PI3K/Akt signaling: its knockdown reduces EGFR, PI3K, and phospho-Akt levels and suppresses proliferation, migration, and invasion [#0]. In pancreatic cancer cells, CAV2 overexpression activates Wnt7A/\\u03b2-catenin signaling and drives invasion and metastasis by inhibiting endocytosis and promoting epithelial-mesenchymal transition, with CAV2 expression negatively regulated by MiR-4723 within a MiR-4723/Wnt7A axis [#1]. Beyond these phenotypic associations, no direct binding, structural, or biochemical reconstitution data establish CAV2's molecular mechanism in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established a pro-tumorigenic role for CAV2 in renal cell carcinoma by placing it upstream of a defined oncogenic signaling pathway.\",\n      \"evidence\": \"siRNA knockdown with wound healing, Matrigel invasion, Western blotting, and orthotopic xenograft in OS-RC-2 cells\",\n      \"pmids\": [\"30288056\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, knockdown-only with Western blot pathway readout; no direct binding or reconstitution establishing the mechanistic link to EGFR/PI3K/Akt\",\n        \"Whether CAV2 physically interacts with EGFR or pathway components is not shown\",\n        \"No structural or biochemical characterization of CAV2 activity\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended CAV2's oncogenic role to pancreatic cancer and connected it to Wnt7A/\\u03b2-catenin signaling, EMT, and upstream microRNA regulation.\",\n      \"evidence\": \"Overexpression/knockdown, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter, and proliferation/invasion/migration assays in pancreatic cancer cells\",\n      \"pmids\": [\"35517414\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab; pathway placement inferred from expression changes after overexpression without direct binding/reconstitution\",\n        \"Mechanism by which CAV2 inhibits endocytosis to modulate signaling is not defined\",\n        \"Direct MiR-4723/CAV2 targeting versus indirect regulation not fully resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular activity, structure, and direct binding partners of CAV2 protein remain undefined.\",\n      \"evidence\": \"No reconstitution, structural, or direct interaction data in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct biochemical or structural characterization of CAV2\",\n        \"No validated physical interaction partners\",\n        \"Mechanism connecting CAV2 to EGFR/PI3K/Akt and Wnt7A/\\u03b2-catenin pathways not established\"\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":"tie","faith_supported":2,"faith_total":2,"faith_pct":100.0}}