{"gene":"CNIH2","run_date":"2026-04-28T17:28:52","timeline":{"discoveries":[{"year":2010,"finding":"CNIH-2 associates with γ-8-containing AMPA receptor complexes in hippocampal postsynaptic densities and abrogates γ-8-mediated resensitization, synergistically modulating AMPAR kinetics and pharmacology. CNIH-2 protein levels are markedly diminished in γ-8 knockout mice, indicating γ-8-dependent stabilization.","method":"Co-immunoprecipitation from postsynaptic densities, electrophysiology in recombinant systems and hippocampal neurons, γ-8 knockout mice","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, genetic KO, electrophysiology; replicated finding across multiple orthogonal methods in same study","pmids":["21172611"],"is_preprint":false},{"year":2013,"finding":"CNIH-2 and CNIH-3 are required for surface expression and synaptic transmission of GluA1-containing AMPARs (GluA1A2 heteromers) in hippocampal neurons; loss of CNIH-2/-3 selectively removes GluA1-containing receptors, leaving a residual pool of GluA2A3 heteromers with faster kinetics. TARP γ-8 prevents functional association of CNIHs with non-GluA1 subunits.","method":"CNIH-2/CNIH-3 conditional knockout mice, whole-cell electrophysiology, surface receptor biochemistry","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — conditional KO with specific cellular phenotype, multiple orthogonal methods, clean genetic dissection","pmids":["23522044"],"is_preprint":false},{"year":2021,"finding":"Cryo-EM structure of native hippocampal AMPA receptor complexes shows that TARP-γ8 and CNIH2 occupy distinct auxiliary subunit positions (B'/D' and A'/C' respectively) beneath the ligand-binding domains of GluA1-GluA2 and GluA2-GluA3 receptors in a non-stochastic arrangement.","method":"Immunoaffinity purification of native hippocampal AMPARs, single-molecule fluorescence, cryo-electron microscopy","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structure of native complex with functional validation; landmark structural study","pmids":["33981040"],"is_preprint":false},{"year":2021,"finding":"Cryo-EM structures of GluA1-GluA2/TARP-γ8/CNIH2 in resting and active states reveal that two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the LBDs, with site-specific lipids shaping each interaction. Upon activation, both auxiliary subunit pairs counter-rotate and pivot toward the pore exit; CNIH2 achieves this through its uniquely extended M2 helix, enabling powerful gating modulation.","method":"Cryo-electron microscopy, structural analysis of resting and active states","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 — cryo-EM structures in two functional states with mechanistic interpretation; orthogonal to PMID 33981040","pmids":["34079129"],"is_preprint":false},{"year":2012,"finding":"CNIH-2 slows deactivation and desensitization of both GluA2-containing and calcium-permeable AMPARs, enhances glutamate sensitivity, single-channel conductance, and calcium permeability of CP-AMPARs, and decreases polyamine block. CNIH-2/3 but not CNIH-1 produce these effects.","method":"Electrophysiology in tsA201 cells, overexpression of CNIH-3 in oligodendrocyte precursor cells, single-channel recordings","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution with biophysical characterization across multiple receptor types and cell contexts","pmids":["22815494"],"is_preprint":false},{"year":2011,"finding":"CNIH-2 coexpression with GluA/TARP complexes reduces TARP stoichiometry within AMPA receptor complexes. In hippocampal neurons, CNIH-2 associates with surface AMPARs in a γ-8-dependent manner to dictate receptor pharmacology; in cerebellum, CNIH-2 does not reach the neuronal surface.","method":"Tandem GluA/TARP fusion constructs to constrain stoichiometry, surface biotinylation, pharmacological profiling, electrophysiology in neurons","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1-2 — stoichiometry-constrained constructs with multiple orthogonal assays","pmids":["21543622"],"is_preprint":false},{"year":2012,"finding":"CNIH-2 serves an evolutionarily conserved cargo exporter role, cycling between ER and Golgi in a COPII-dependent manner. GluA subunits recruit CNIH-2 to the cell surface, commandeering it from its ancestral ER-export role to function as a bona fide auxiliary subunit.","method":"Live-cell imaging of ER-Golgi cycling, COPII-dependent export assays, heterologous cell expression, primary rat neurons","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 — live imaging with functional consequence, multiple orthogonal approaches demonstrating ER-Golgi cycling","pmids":["22292017"],"is_preprint":false},{"year":2014,"finding":"CNIH2-containing AMPARs dictate the slow decay of EPSCs at hippocampal mossy fiber bouton–hilar mossy cell synapses. Selective knockdown of CNIH2 markedly accelerated EPSC decay without altering amplitude; viral expression of CNIH2 in aspiny interneurons (which normally lack it) slowed their fast EPSCs.","method":"Paired whole-cell recordings, selective knockdown via shRNA, virus-directed CNIH2 expression","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 — loss-of-function and gain-of-function at defined identified synapses with specific electrophysiological readout","pmids":["24853943"],"is_preprint":false},{"year":2014,"finding":"CNIH-3 forms a stable complex with tetrameric AMPARs contributing to transmembrane density. Two clusters of conserved membrane-proximal residues mediate AMPAR binding; residues in the extracellular loop of CNIH-2/3 absent in CNIH-1/4 are critical for both AMPAR interaction and gating modulation. The AMPAR ligand-binding domain is the principal contact point for the CNIH-3 extracellular loop.","method":"Single-particle electron microscopy, peptide array screening, in vitro mutagenesis, binding and gating assays","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1 — structural EM, mutagenesis, and functional gating assays in same study","pmids":["25186755"],"is_preprint":false},{"year":2011,"finding":"CNIH-2 differentially modulates AMPAR gating depending on TARP isoform: with γ-8 (hippocampal), CNIH-2 slows deactivation, increases cyclothiazide potency and occludes resensitization; with γ-2 (cerebellar), CNIH-2 has minimal kinetic effects but decreases IKA/IGlu ratio.","method":"Electrophysiology in recombinant expression systems with defined TARP isoforms, pharmacological profiling","journal":"The European journal of neuroscience","confidence":"High","confidence_rationale":"Tier 1-2 — systematic electrophysiology across isoforms with clear mechanistic dissection","pmids":["22211840"],"is_preprint":false},{"year":2011,"finding":"CNIH-2 allosterically modifies AMPA receptor pharmacology, conferring partial sensitivity of potentiator binding to displacement by non-competitive antagonists in a manner that depends on the auxiliary subunit composition of the receptor complex.","method":"Radioligand binding assays ([3H]-LY450295), autoradiography in brain sections from stargazer and γ-8 KO mice","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — radioligand binding with KO mice, but single lab and primarily pharmacological readout","pmids":["21343286"],"is_preprint":false},{"year":2013,"finding":"CNIH-2 and CNIH-3 associate with GluA subunits in the early secretory pathway; during ontogeny, an excess of AMPAR-free CNIH-2/3 exists early postnatally (consistent with ER cargo exporter role) but shifts toward AMPAR-integrated forms during development.","method":"Developmental expression profiling, co-immunoprecipitation, subcellular fractionation in rat brain","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2-3 — Co-IP and fractionation across developmental timepoints; single lab","pmids":["23403072"],"is_preprint":false},{"year":2016,"finding":"GSG1L association with AMPARs inhibits CNIH2-induced slowing of receptor kinetics in heterologous cells, defining a competitive or antagonistic relationship between these two auxiliary subunits in modulating AMPAR deactivation and desensitization.","method":"Electrophysiology in heterologous cells with co-expression of GSG1L and CNIH2","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 — functional electrophysiology in recombinant system; single lab but clear mechanistic result","pmids":["26932439"],"is_preprint":false},{"year":2018,"finding":"SAP102-mediated rescue of AMPAR-mediated synaptic transmission requires CNIH-2; knockdown of CNIH-2 abolishes the SAP102-dependent increase in AMPAR EPSC decay time, placing CNIH-2 downstream of SAP102 in regulating synaptic AMPAR kinetics.","method":"Cell-restricted molecular replacement of PSD-95 with SAP102, CNIH-2 knockdown, whole-cell electrophysiology","journal":"Journal of neurophysiology","confidence":"Medium","confidence_rationale":"Tier 2 — epistasis established by genetic replacement strategy with electrophysiological readout; single lab","pmids":["30067114"],"is_preprint":false},{"year":2007,"finding":"CNIH2 (cornichon-like protein/CNIL) facilitates secretion of HB-EGF in a cell culture system, and its perturbation in chick embryos (by truncated CNIH expression or siRNA knockdown) disrupts neural crest cell distribution and cranial nerve development, phenocopying ErbB4 knockout.","method":"Cell culture secretion assay, chick embryo dominant-negative overexpression and siRNA knockdown, in situ hybridization","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function in vivo with defined phenotypic readout and cell culture secretion assay; chick ortholog study","pmids":["17229890"],"is_preprint":false},{"year":2016,"finding":"Knockdown of PORCN in hippocampal neurons leads to depletion of TARP γ-8 from AMPAR complexes, demonstrating that PORCN regulates the composition of AMPAR auxiliary subunit assemblies including CNIH-2/3-containing complexes.","method":"Immunoprecipitation of AMPAR complexes, PORCN knockdown and conditional KO, electrophysiology","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP and KO with defined biochemical and functional readout; CNIH-2 as part of the complex rather than primary focus","pmids":["26776514"],"is_preprint":false},{"year":2023,"finding":"CNIH-2 enhances tetramerization of wild-type and mutant AMPARs, primarily through interactions with the transmembrane domain of the receptor, and promotes surface expression more effectively than TARP γ-2. CNIH-2 enhances both GluA1 and GluA2 tetramerization, whereas CNIH-3 only weakly enhances GluA1 tetramerization.","method":"In vitro tetramerization assays, surface expression assays in heterologous cells, mutagenesis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1-2 — in vitro assay with mutagenesis; single lab","pmids":["37673338"],"is_preprint":false},{"year":2022,"finding":"Interaction proteomics demonstrates that CNIH-2 co-purifies with highest abundance in GluA1/2 receptor complexes alongside TARP-γ8 and SynDIG4, and also co-purifies strongly with GluA2/3 receptors, revealing subtype-specific AMPAR–auxiliary subunit associations.","method":"Interaction proteomics (immunoprecipitation–mass spectrometry) from Gria1 and Gria3 knockout mouse hippocampi","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 — MS-based interactome from KO mice; single lab","pmids":["36429079"],"is_preprint":false},{"year":2024,"finding":"CPSF3 promotes CNIH2 expression in esophageal squamous cell carcinoma by inducing use of a proximal poly(A) site in the CNIH2 3'UTR, thereby preventing miR-125a-5p-mediated repression of CNIH2 mRNA. CPSF3-induced tumorigenicity is mediated by CNIH2, as CNIH2 knockdown inhibits ESCC cell proliferation, migration, invasion, and tumor growth in vivo.","method":"Iso-Seq and RNA-seq APA analysis, CPSF3 knockdown/overexpression, colony formation/transwell assays, xenograft experiments, luciferase reporter for miRNA binding","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined molecular mechanism (APA/miRNA) and in vivo xenograft; single lab","pmids":["38718887"],"is_preprint":false},{"year":2025,"finding":"CNIH-2 mRNA is locally translated in dendrites, and this local synthesis increases after chemical LTP induction. Local CNIH-2 translation is required for plasma membrane insertion of GluA2-containing (calcium-impermeable) AMPARs but not GluA1-homomeric AMPARs, selectively enabling slow-response AMPAR trafficking after plasticity induction.","method":"Dendritic mRNA localization assays, local translation reporters, chemical LTP induction, selective trafficking assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — multiple experimental approaches including local translation inhibition and LTP paradigm; preprint, not yet peer-reviewed","pmids":["bio_10.1101_2025.02.08.637220"],"is_preprint":true}],"current_model":"CNIH2 is a transmembrane auxiliary subunit of hippocampal AMPA receptors that occupies defined positions (A'/C') in the native receptor complex alongside TARP-γ8, where its extended M2 helix pivots toward the pore upon activation to slow AMPAR deactivation and desensitization, reduce desensitization, enhance single-channel conductance and calcium permeability, promote GluA tetramerization and ER-to-surface trafficking in a COPII-dependent manner, and synergize with TARP-γ8 to dictate the subunit composition, kinetics, and pharmacology of synaptic AMPARs in hippocampal neurons; additionally, CNIH2 mRNA is locally translated in dendrites and this local synthesis is selectively required for LTP-induced membrane insertion of GluA2-containing receptors."},"narrative":{"teleology":[{"year":2007,"claim":"Before CNIH2 was linked to AMPA receptors, its ancestral role as a secretory pathway cargo exporter was established: CNIH2 facilitated HB-EGF secretion and its perturbation disrupted neural crest cell migration and cranial nerve patterning in chick embryos, revealing a developmental function through growth factor export.","evidence":"Cell culture secretion assay, dominant-negative and siRNA knockdown in chick embryos with phenotypic analysis","pmids":["17229890"],"confidence":"Medium","gaps":["Chick ortholog study; relevance to mammalian CNIH2 function not directly tested","Mechanism of selective cargo recognition for HB-EGF not defined","Relationship to AMPAR biology unknown at this point"]},{"year":2010,"claim":"The discovery that CNIH2 physically associates with γ-8-containing AMPAR complexes in hippocampal postsynaptic densities established it as a neuronal AMPAR auxiliary subunit rather than merely an ER export factor; CNIH2 synergized with TARP-γ8 to modulate receptor kinetics and pharmacology, and its protein stability depended on γ-8.","evidence":"Reciprocal co-immunoprecipitation from PSDs, electrophysiology in recombinant systems and hippocampal neurons, γ-8 knockout mice","pmids":["21172611"],"confidence":"High","gaps":["Structural basis of CNIH2–TARP–AMPAR interaction unknown","Whether CNIH2 reaches the neuronal surface independently of γ-8 was unclear"]},{"year":2011,"claim":"Systematic electrophysiological and pharmacological profiling revealed that CNIH2's gating modulation is TARP-isoform-dependent — slowing deactivation and occluding resensitization with γ-8 but having minimal kinetic effects with γ-2 — explaining region-specific AMPAR properties and showing that CNIH2 reduces TARP stoichiometry within receptor complexes.","evidence":"Electrophysiology with defined TARP isoforms in recombinant systems, tandem GluA/TARP stoichiometry-constrained constructs, surface biotinylation, radioligand binding with KO mice","pmids":["21543622","22211840","21343286"],"confidence":"High","gaps":["Mechanism of stoichiometric competition between CNIH2 and TARPs at the molecular level unresolved","In vivo consequences of pharmacological modulation not tested"]},{"year":2012,"claim":"Two key properties of CNIH2 were mechanistically dissected: it cycles between ER and Golgi in a COPII-dependent manner (fulfilling an ancestral cargo export role that GluA subunits commandeer for surface delivery), and it enhances single-channel conductance, calcium permeability, and glutamate sensitivity of both CI- and CP-AMPARs.","evidence":"Live-cell imaging of ER-Golgi cycling, COPII export assays, single-channel recordings in heterologous cells","pmids":["22292017","22815494"],"confidence":"High","gaps":["How GluA subunits redirect CNIH2 from ER cycling to surface retention not structurally defined","Whether COPII-dependent export is rate-limiting for synaptic AMPAR delivery in vivo unknown"]},{"year":2013,"claim":"Conditional knockout of CNIH2/3 in hippocampal neurons demonstrated a non-redundant requirement for surface expression and synaptic transmission of GluA1-containing AMPARs, with loss selectively removing GluA1A2 heteromers and leaving faster-kinetics GluA2A3 receptors — establishing CNIH2/3 as gatekeepers of AMPAR subunit composition at synapses.","evidence":"CNIH-2/CNIH-3 conditional knockout mice, whole-cell electrophysiology, surface receptor biochemistry, developmental co-IP","pmids":["23522044","23403072"],"confidence":"High","gaps":["Whether CNIH2 and CNIH3 have distinct or fully redundant roles not fully separated","Downstream signaling consequences of altered subunit composition not explored"]},{"year":2014,"claim":"At identified hippocampal synapses, CNIH2 was shown to be the primary determinant of slow EPSC decay: knockdown accelerated mossy fiber–hilar mossy cell EPSCs, and ectopic expression in fast-EPSC interneurons slowed their kinetics, while structural work on CNIH3 identified the extracellular loop and membrane-proximal residues as critical for AMPAR binding and gating modulation.","evidence":"Paired whole-cell recordings with shRNA knockdown and viral gain-of-function; single-particle EM, peptide array screening, mutagenesis","pmids":["24853943","25186755"],"confidence":"High","gaps":["Whether all hippocampal synapse types use CNIH2 to set kinetics not surveyed","Precise structural contacts between CNIH2 extracellular loop and AMPAR LBD not resolved at atomic level"]},{"year":2016,"claim":"The auxiliary subunit GSG1L was found to antagonize CNIH2-mediated slowing of AMPAR kinetics, revealing a competitive regulatory axis among auxiliary subunits, while PORCN was shown to regulate TARP-γ8 incorporation into AMPAR complexes including those containing CNIH2.","evidence":"Electrophysiology with GSG1L/CNIH2 co-expression; PORCN knockdown/KO with co-IP and electrophysiology","pmids":["26932439","26776514"],"confidence":"Medium","gaps":["Whether GSG1L-CNIH2 competition occurs at the same binding site or allosterically is unknown","In vivo relevance of GSG1L–CNIH2 antagonism at specific synapses not demonstrated"]},{"year":2021,"claim":"Cryo-EM structures of native and reconstituted AMPAR complexes revealed the atomic-level architecture: CNIH2 and TARP-γ8 occupy non-equivalent positions (A'/C' and B'/D' respectively) with site-specific lipids, and upon receptor activation CNIH2's uniquely extended M2 helix counter-rotates and pivots toward the pore exit, providing the structural basis for its powerful gating modulation.","evidence":"Cryo-EM of native hippocampal AMPARs and reconstituted GluA1-GluA2/γ8/CNIH2 in resting and active states","pmids":["33981040","34079129"],"confidence":"High","gaps":["Desensitized-state structure with CNIH2 not resolved","How lipid specificity at CNIH2 vs TARP sites affects function not tested","Structures of complexes with other auxiliary subunit combinations lacking"]},{"year":2023,"claim":"CNIH2 was found to promote AMPAR tetramerization through transmembrane domain interactions more effectively than TARP-γ2, revealing a previously unrecognized role in receptor assembly upstream of ER export.","evidence":"In vitro tetramerization assays, surface expression assays, mutagenesis in heterologous cells","pmids":["37673338"],"confidence":"Medium","gaps":["Whether tetramerization enhancement is rate-limiting for AMPAR biogenesis in neurons not shown","Structural basis of TMD-mediated tetramerization promotion not determined"]},{"year":2024,"claim":"Outside the nervous system, CNIH2 was implicated in esophageal squamous cell carcinoma tumorigenicity, where CPSF3 promotes CNIH2 expression by inducing proximal poly(A) site usage that evades miR-125a-5p-mediated mRNA repression.","evidence":"APA analysis, CPSF3/CNIH2 knockdown and overexpression, xenograft tumor models, luciferase reporters","pmids":["38718887"],"confidence":"Medium","gaps":["Whether CNIH2's tumorigenic role acts through AMPAR signaling or an AMPAR-independent mechanism is unknown","Single cancer type studied; generalizability not established"]},{"year":null,"claim":"Key unresolved questions include: (1) the structural mechanism by which CNIH2 promotes tetramerization through TMD contacts, (2) how local dendritic translation of CNIH2 mRNA selectively enables GluA2-containing AMPAR insertion during LTP, (3) whether CNIH2 functions independently of AMPARs in non-neuronal contexts such as cancer, and (4) how the CNIH2–GSG1L competitive axis is regulated in vivo at specific synapse types.","evidence":"","pmids":[],"confidence":"Low","gaps":["No desensitized-state cryo-EM structure with CNIH2","Local translation findings from preprint not yet peer-reviewed","No CNIH2-specific knockout (separate from CNIH3) phenotype fully characterized in behavior"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,4,7,9,12]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,3,8,16]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,5,6,16]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[6,11]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[6]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,1,4,7,9]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[6,16]},{"term_id":"R-HSA-382551","term_label":"Transport of small molecules","supporting_discovery_ids":[0,4,5]}],"complexes":["AMPAR-TARP-γ8-CNIH2 complex","GluA1-GluA2/γ8/CNIH2 complex","GluA2-GluA3/γ8/CNIH2 complex"],"partners":["GRIA1","GRIA2","GRIA3","CACNG8","SAP102","GSG1L","CNIH3","PORCN"],"other_free_text":[]},"mechanistic_narrative":"CNIH2 is a transmembrane auxiliary subunit of AMPA-type glutamate receptors that modulates receptor assembly, trafficking, gating kinetics, and synaptic transmission in hippocampal neurons. CNIH2 associates with AMPAR complexes in a TARP-γ8-dependent manner, occupying defined positions (A'/C') in the native receptor architecture where its extended M2 helix pivots toward the pore upon activation to slow deactivation and desensitization, enhance single-channel conductance and calcium permeability, and shape synapse-specific EPSC kinetics [PMID:21172611, PMID:34079129, PMID:24853943]. Beyond gating modulation, CNIH2 promotes GluA subunit tetramerization through transmembrane domain interactions and facilitates ER-to-surface receptor trafficking via COPII-dependent export, functioning as both a cargo exporter and a bona fide auxiliary subunit [PMID:22292017, PMID:37673338]. Conditional loss of CNIH2/3 selectively removes GluA1-containing AMPARs from hippocampal synapses, demonstrating a non-redundant role in determining the subunit composition and kinetic identity of synaptic receptor pools [PMID:23522044, PMID:22815494]."},"prefetch_data":{"uniprot":{"accession":"Q6PI25","full_name":"Protein cornichon homolog 2","aliases":["Cornichon family AMPA receptor auxiliary protein 2","Cornichon-like protein"],"length_aa":160,"mass_kda":18.9,"function":"Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by regulating their rates of activation, deactivation and desensitization. Blocks CACNG8-mediated resensitization of AMPA receptors","subcellular_location":"Endoplasmic reticulum membrane; Postsynaptic cell membrane; Cell projection, dendrite; Cell projection, dendritic spine; Postsynaptic density","url":"https://www.uniprot.org/uniprotkb/Q6PI25/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CNIH2","classification":"Not Classified","n_dependent_lines":45,"n_total_lines":1208,"dependency_fraction":0.037251655629139076},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CNIH2","total_profiled":1310},"omim":[{"mim_id":"617492","title":"OLFACTOMEDIN 2; OLFM2","url":"https://www.omim.org/entry/617492"},{"mim_id":"617483","title":"CORNICHON FAMILY AMPA RECEPTOR AUXILIARY PROTEIN 4; CNIH4","url":"https://www.omim.org/entry/617483"},{"mim_id":"617161","title":"GSG1-LIKE PROTEIN; GSG1L","url":"https://www.omim.org/entry/617161"},{"mim_id":"611288","title":"CORNICHON FAMILY AMPA RECEPTOR AUXILIARY PROTEIN 2; CNIH2","url":"https://www.omim.org/entry/611288"},{"mim_id":"611287","title":"CORNICHON FAMILY AMPA RECEPTOR AUXILIARY PROTEIN 1; CNIH1","url":"https://www.omim.org/entry/611287"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":424.2}],"url":"https://www.proteinatlas.org/search/CNIH2"},"hgnc":{"alias_symbol":["MGC50896","Cnil","CNIH-2"],"prev_symbol":[]},"alphafold":{"accession":"Q6PI25","domains":[{"cath_id":"-","chopping":"4-158","consensus_level":"high","plddt":87.3848,"start":4,"end":158}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PI25","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PI25-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6PI25-F1-predicted_aligned_error_v6.png","plddt_mean":87.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CNIH2","jax_strain_url":"https://www.jax.org/strain/search?query=CNIH2"},"sequence":{"accession":"Q6PI25","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6PI25.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6PI25/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6PI25"}},"corpus_meta":[{"pmid":"21172611","id":"PMC_21172611","title":"Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins.","date":"2010","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/21172611","citation_count":142,"is_preprint":false},{"pmid":"25646370","id":"PMC_25646370","title":"Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.","date":"2015","source":"Annals of the rheumatic diseases","url":"https://pubmed.ncbi.nlm.nih.gov/25646370","citation_count":139,"is_preprint":false},{"pmid":"23522044","id":"PMC_23522044","title":"Cornichon proteins determine the subunit composition of synaptic AMPA receptors.","date":"2013","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/23522044","citation_count":126,"is_preprint":false},{"pmid":"33981040","id":"PMC_33981040","title":"Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/33981040","citation_count":91,"is_preprint":false},{"pmid":"22815494","id":"PMC_22815494","title":"Cornichons modify channel properties of recombinant and glial AMPA receptors.","date":"2012","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22815494","citation_count":86,"is_preprint":false},{"pmid":"26932439","id":"PMC_26932439","title":"GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26932439","citation_count":73,"is_preprint":false},{"pmid":"21543622","id":"PMC_21543622","title":"Cornichon-2 modulates AMPA receptor-transmembrane AMPA receptor regulatory protein assembly to dictate gating and pharmacology.","date":"2011","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/21543622","citation_count":62,"is_preprint":false},{"pmid":"34079129","id":"PMC_34079129","title":"Gating and modulation of a hetero-octameric AMPA glutamate receptor.","date":"2021","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/34079129","citation_count":59,"is_preprint":false},{"pmid":"26553698","id":"PMC_26553698","title":"Efficacy of ex vivo autologous and in vivo platelet transfusion in the reversal of P2Y12 inhibition by clopidogrel, prasugrel, and ticagrelor: the APTITUDE study.","date":"2015","source":"Circulation. Cardiovascular interventions","url":"https://pubmed.ncbi.nlm.nih.gov/26553698","citation_count":59,"is_preprint":false},{"pmid":"33811291","id":"PMC_33811291","title":"3D-Image guided robotic-assisted partial nephrectomy: a multi-institutional propensity score-matched analysis (UroCCR study 51).","date":"2021","source":"World journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/33811291","citation_count":46,"is_preprint":false},{"pmid":"24853943","id":"PMC_24853943","title":"Cornichon2 dictates the time course of excitatory transmission at individual hippocampal synapses.","date":"2014","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/24853943","citation_count":45,"is_preprint":false},{"pmid":"26776514","id":"PMC_26776514","title":"Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission.","date":"2016","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26776514","citation_count":41,"is_preprint":false},{"pmid":"22292017","id":"PMC_22292017","title":"AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22292017","citation_count":38,"is_preprint":false},{"pmid":"30552145","id":"PMC_30552145","title":"A placental mammal-specific microRNA cluster acts as a natural brake for sociability in mice.","date":"2018","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/30552145","citation_count":37,"is_preprint":false},{"pmid":"25218043","id":"PMC_25218043","title":"Deletion of olfactomedin 2 induces changes in the AMPA receptor complex and impairs visual, olfactory, and motor functions in mice.","date":"2014","source":"Experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/25218043","citation_count":32,"is_preprint":false},{"pmid":"22211840","id":"PMC_22211840","title":"AMPA receptor modulation by cornichon-2 dictated by transmembrane AMPA receptor regulatory protein isoform.","date":"2011","source":"The European journal of neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/22211840","citation_count":31,"is_preprint":false},{"pmid":"25186755","id":"PMC_25186755","title":"Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3.","date":"2014","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/25186755","citation_count":29,"is_preprint":false},{"pmid":"17229890","id":"PMC_17229890","title":"Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17229890","citation_count":22,"is_preprint":false},{"pmid":"32810206","id":"PMC_32810206","title":"Added value of buccal cell FISH analysis in the diagnosis and management of Turner syndrome.","date":"2020","source":"Human reproduction (Oxford, England)","url":"https://pubmed.ncbi.nlm.nih.gov/32810206","citation_count":21,"is_preprint":false},{"pmid":"23103966","id":"PMC_23103966","title":"Upregulation of cornichon transcripts in the dorsolateral prefrontal cortex in schizophrenia.","date":"2012","source":"Neuroreport","url":"https://pubmed.ncbi.nlm.nih.gov/23103966","citation_count":20,"is_preprint":false},{"pmid":"34830961","id":"PMC_34830961","title":"The Cardiac Glycoside Deslanoside Exerts Anticancer Activity in Prostate Cancer Cells by Modulating Multiple Signaling Pathways.","date":"2021","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/34830961","citation_count":20,"is_preprint":false},{"pmid":"23426437","id":"PMC_23426437","title":"Auxiliary subunits provide new insights into regulation of AMPA receptor trafficking.","date":"2013","source":"Journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23426437","citation_count":17,"is_preprint":false},{"pmid":"22986108","id":"PMC_22986108","title":"A 1 Mb de novo deletion within 11q13.1q13.2 in a boy with mild intellectual disability and minor dysmorphic features.","date":"2012","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22986108","citation_count":17,"is_preprint":false},{"pmid":"21343286","id":"PMC_21343286","title":"Transmembrane AMPA receptor regulatory proteins and cornichon-2 allosterically regulate AMPA receptor antagonists and potentiators.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21343286","citation_count":17,"is_preprint":false},{"pmid":"36429079","id":"PMC_36429079","title":"Expression and Interaction Proteomics of GluA1- and GluA3-Subunit-Containing AMPARs Reveal Distinct Protein Composition.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/36429079","citation_count":16,"is_preprint":false},{"pmid":"28392828","id":"PMC_28392828","title":"Screening of Wilson's disease in a psychiatric population: difficulties and pitfalls. A preliminary study.","date":"2017","source":"Annals of general psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/28392828","citation_count":16,"is_preprint":false},{"pmid":"23403072","id":"PMC_23403072","title":"Ontogeny repeats the phylogenetic recruitment of the cargo exporter cornichon into AMPA receptor signaling complexes.","date":"2013","source":"Molecular and cellular neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/23403072","citation_count":13,"is_preprint":false},{"pmid":"10022955","id":"PMC_10022955","title":"The mouse cornichon gene family.","date":"1999","source":"Development genes and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/10022955","citation_count":12,"is_preprint":false},{"pmid":"25495042","id":"PMC_25495042","title":"TARP γ-8 glycosylation regulates the surface expression of AMPA receptors.","date":"2015","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/25495042","citation_count":11,"is_preprint":false},{"pmid":"26255765","id":"PMC_26255765","title":"Advances in the pharmacology of lGICs auxiliary subunits.","date":"2015","source":"Pharmacological research","url":"https://pubmed.ncbi.nlm.nih.gov/26255765","citation_count":11,"is_preprint":false},{"pmid":"30067114","id":"PMC_30067114","title":"SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism.","date":"2018","source":"Journal of neurophysiology","url":"https://pubmed.ncbi.nlm.nih.gov/30067114","citation_count":10,"is_preprint":false},{"pmid":"31696922","id":"PMC_31696922","title":"Dental and craniofacial features associated with GNAS loss of function mutations.","date":"2020","source":"European journal of orthodontics","url":"https://pubmed.ncbi.nlm.nih.gov/31696922","citation_count":10,"is_preprint":false},{"pmid":"33765164","id":"PMC_33765164","title":"Predictive factors of recurrence after surgery in patients with non-metastatic renal cell carcinoma with venous tumor thrombus (UroCCR-56 Study).","date":"2021","source":"World journal of urology","url":"https://pubmed.ncbi.nlm.nih.gov/33765164","citation_count":9,"is_preprint":false},{"pmid":"25792422","id":"PMC_25792422","title":"Prolonged glutamate excitotoxicity increases GluR1 immunoreactivity but decreases mRNA of GluR1 and associated regulatory proteins in dissociated rat retinae in vitro.","date":"2015","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/25792422","citation_count":9,"is_preprint":false},{"pmid":"35178068","id":"PMC_35178068","title":"Genome Sequencing for Genetics Diagnosis of Patients With Intellectual Disability: The DEFIDIAG Study.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35178068","citation_count":9,"is_preprint":false},{"pmid":"32437423","id":"PMC_32437423","title":"Impact of introducing a standardized nutrition protocol on very premature infants' growth and morbidity.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32437423","citation_count":8,"is_preprint":false},{"pmid":"37052186","id":"PMC_37052186","title":"A cornichon protein controls polar localization of the PINA auxin transporter in Physcomitrium patens.","date":"2023","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/37052186","citation_count":7,"is_preprint":false},{"pmid":"32880091","id":"PMC_32880091","title":"Immediate preoperative renal artery embolization in the resection of complex renal tumors (UroCCR-48 Reinbol study).","date":"2020","source":"International urology and nephrology","url":"https://pubmed.ncbi.nlm.nih.gov/32880091","citation_count":7,"is_preprint":false},{"pmid":"37673338","id":"PMC_37673338","title":"Differential regulation of tetramerization of the AMPA receptor glutamate-gated ion channel by auxiliary subunits.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37673338","citation_count":6,"is_preprint":false},{"pmid":"34177466","id":"PMC_34177466","title":"Auxiliary Subunits Control Function and Subcellular Distribution of AMPA Receptor Complexes in NG2 Glia of the Developing Hippocampus.","date":"2021","source":"Frontiers in cellular neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/34177466","citation_count":6,"is_preprint":false},{"pmid":"38718887","id":"PMC_38718887","title":"CPSF3 regulates alternative polyadenylation of CNIH2 to promote esophageal squamous cell carcinoma progression.","date":"2024","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/38718887","citation_count":5,"is_preprint":false},{"pmid":"38331895","id":"PMC_38331895","title":"Pancreatic enzyme replacement therapy in subjects with exocrine pancreatic insufficiency and diabetes mellitus: a real-life, case-control study.","date":"2024","source":"Diabetology & metabolic syndrome","url":"https://pubmed.ncbi.nlm.nih.gov/38331895","citation_count":5,"is_preprint":false},{"pmid":"36911413","id":"PMC_36911413","title":"Imaging genetic association analysis of triple-negative breast cancer based on the integration of prior sample information.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36911413","citation_count":3,"is_preprint":false},{"pmid":"38492119","id":"PMC_38492119","title":"Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.","date":"2024","source":"Journal of robotic surgery","url":"https://pubmed.ncbi.nlm.nih.gov/38492119","citation_count":3,"is_preprint":false},{"pmid":"38836370","id":"PMC_38836370","title":"The Role of Cornichons in the Biogenesis and Functioning of Monovalent-Cation Transport Systems.","date":"2024","source":"Physiological research","url":"https://pubmed.ncbi.nlm.nih.gov/38836370","citation_count":2,"is_preprint":false},{"pmid":"36798164","id":"PMC_36798164","title":"Differential regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) receptor tetramerization by auxiliary subunits.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36798164","citation_count":1,"is_preprint":false},{"pmid":"41026898","id":"PMC_41026898","title":"Predicting cardiovascular events in allogeneic haematopoietic stem cell transplant recipients.","date":"2026","source":"European journal of preventive cardiology","url":"https://pubmed.ncbi.nlm.nih.gov/41026898","citation_count":1,"is_preprint":false},{"pmid":"41127817","id":"PMC_41127817","title":"Multifaceted disruption of AMPA receptor signaling by CACNG8 variants: Integrated evidence from human genetics and molecular simulation.","date":"2025","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/41127817","citation_count":1,"is_preprint":false},{"pmid":"35444683","id":"PMC_35444683","title":"The Economic, Medical and Psychosocial Consequences of Whole Genome Sequencing for the Genetic Diagnosis of Patients With Intellectual Disability: The DEFIDIAG Study Protocol.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35444683","citation_count":1,"is_preprint":false},{"pmid":"31193495","id":"PMC_31193495","title":"Inyección Intraarticular Única de Ácido Hialurónico en la Artrosis de Rodilla: Estudio Multicéntrico Prospectivo Abierto (ART-ONE 75) mediante Comparación Post-Hoc con Placebo.","date":"2019","source":"Current therapeutic research, clinical and experimental","url":"https://pubmed.ncbi.nlm.nih.gov/31193495","citation_count":1,"is_preprint":false},{"pmid":"39433941","id":"PMC_39433941","title":"Expression and role of CNIH2 in prostate cancer.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39433941","citation_count":0,"is_preprint":false},{"pmid":"39825254","id":"PMC_39825254","title":"Are psychological attitudes towards vaccination an expression of personality? A cross-sectional study on COVID-19 vaccination in France.","date":"2025","source":"BMC public health","url":"https://pubmed.ncbi.nlm.nih.gov/39825254","citation_count":0,"is_preprint":false},{"pmid":"41676957","id":"PMC_41676957","title":"Trafficking of the human Na+/H+ antiporter NHA2 to the plasma membrane requires cornichon COPII cargo receptors.","date":"2026","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/41676957","citation_count":0,"is_preprint":false},{"pmid":"40595792","id":"PMC_40595792","title":"Modeling the use of transient ligand binding information by AMPA receptors.","date":"2025","source":"NPJ systems biology and applications","url":"https://pubmed.ncbi.nlm.nih.gov/40595792","citation_count":0,"is_preprint":false},{"pmid":"41644158","id":"PMC_41644158","title":"Doravirine versus dolutegravir-based regimen in antiretroviral treatment-naive people living with HIV-1 (ANRS0392s ELDORADO): protocol for an international, open-label, randomised, non-inferiority, phase III trial.","date":"2026","source":"BMJ open","url":"https://pubmed.ncbi.nlm.nih.gov/41644158","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.02.08.637220","title":"An integrative model of AMPA receptor trafficking reveals the central contribution of local translation in subtype-specific kinetics","date":"2025-02-08","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.08.637220","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":33115,"output_tokens":4704,"usd":0.084953},"stage2":{"model":"claude-opus-4-6","input_tokens":8248,"output_tokens":3258,"usd":0.184035},"total_usd":0.268988,"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\": 2010,\n      \"finding\": \"CNIH-2 associates with γ-8-containing AMPA receptor complexes in hippocampal postsynaptic densities and abrogates γ-8-mediated resensitization, synergistically modulating AMPAR kinetics and pharmacology. CNIH-2 protein levels are markedly diminished in γ-8 knockout mice, indicating γ-8-dependent stabilization.\",\n      \"method\": \"Co-immunoprecipitation from postsynaptic densities, electrophysiology in recombinant systems and hippocampal neurons, γ-8 knockout mice\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, genetic KO, electrophysiology; replicated finding across multiple orthogonal methods in same study\",\n      \"pmids\": [\"21172611\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CNIH-2 and CNIH-3 are required for surface expression and synaptic transmission of GluA1-containing AMPARs (GluA1A2 heteromers) in hippocampal neurons; loss of CNIH-2/-3 selectively removes GluA1-containing receptors, leaving a residual pool of GluA2A3 heteromers with faster kinetics. TARP γ-8 prevents functional association of CNIHs with non-GluA1 subunits.\",\n      \"method\": \"CNIH-2/CNIH-3 conditional knockout mice, whole-cell electrophysiology, surface receptor biochemistry\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO with specific cellular phenotype, multiple orthogonal methods, clean genetic dissection\",\n      \"pmids\": [\"23522044\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM structure of native hippocampal AMPA receptor complexes shows that TARP-γ8 and CNIH2 occupy distinct auxiliary subunit positions (B'/D' and A'/C' respectively) beneath the ligand-binding domains of GluA1-GluA2 and GluA2-GluA3 receptors in a non-stochastic arrangement.\",\n      \"method\": \"Immunoaffinity purification of native hippocampal AMPARs, single-molecule fluorescence, cryo-electron microscopy\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structure of native complex with functional validation; landmark structural study\",\n      \"pmids\": [\"33981040\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM structures of GluA1-GluA2/TARP-γ8/CNIH2 in resting and active states reveal that two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the LBDs, with site-specific lipids shaping each interaction. Upon activation, both auxiliary subunit pairs counter-rotate and pivot toward the pore exit; CNIH2 achieves this through its uniquely extended M2 helix, enabling powerful gating modulation.\",\n      \"method\": \"Cryo-electron microscopy, structural analysis of resting and active states\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — cryo-EM structures in two functional states with mechanistic interpretation; orthogonal to PMID 33981040\",\n      \"pmids\": [\"34079129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CNIH-2 slows deactivation and desensitization of both GluA2-containing and calcium-permeable AMPARs, enhances glutamate sensitivity, single-channel conductance, and calcium permeability of CP-AMPARs, and decreases polyamine block. CNIH-2/3 but not CNIH-1 produce these effects.\",\n      \"method\": \"Electrophysiology in tsA201 cells, overexpression of CNIH-3 in oligodendrocyte precursor cells, single-channel recordings\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution with biophysical characterization across multiple receptor types and cell contexts\",\n      \"pmids\": [\"22815494\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CNIH-2 coexpression with GluA/TARP complexes reduces TARP stoichiometry within AMPA receptor complexes. In hippocampal neurons, CNIH-2 associates with surface AMPARs in a γ-8-dependent manner to dictate receptor pharmacology; in cerebellum, CNIH-2 does not reach the neuronal surface.\",\n      \"method\": \"Tandem GluA/TARP fusion constructs to constrain stoichiometry, surface biotinylation, pharmacological profiling, electrophysiology in neurons\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — stoichiometry-constrained constructs with multiple orthogonal assays\",\n      \"pmids\": [\"21543622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CNIH-2 serves an evolutionarily conserved cargo exporter role, cycling between ER and Golgi in a COPII-dependent manner. GluA subunits recruit CNIH-2 to the cell surface, commandeering it from its ancestral ER-export role to function as a bona fide auxiliary subunit.\",\n      \"method\": \"Live-cell imaging of ER-Golgi cycling, COPII-dependent export assays, heterologous cell expression, primary rat neurons\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — live imaging with functional consequence, multiple orthogonal approaches demonstrating ER-Golgi cycling\",\n      \"pmids\": [\"22292017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CNIH2-containing AMPARs dictate the slow decay of EPSCs at hippocampal mossy fiber bouton–hilar mossy cell synapses. Selective knockdown of CNIH2 markedly accelerated EPSC decay without altering amplitude; viral expression of CNIH2 in aspiny interneurons (which normally lack it) slowed their fast EPSCs.\",\n      \"method\": \"Paired whole-cell recordings, selective knockdown via shRNA, virus-directed CNIH2 expression\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function and gain-of-function at defined identified synapses with specific electrophysiological readout\",\n      \"pmids\": [\"24853943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"CNIH-3 forms a stable complex with tetrameric AMPARs contributing to transmembrane density. Two clusters of conserved membrane-proximal residues mediate AMPAR binding; residues in the extracellular loop of CNIH-2/3 absent in CNIH-1/4 are critical for both AMPAR interaction and gating modulation. The AMPAR ligand-binding domain is the principal contact point for the CNIH-3 extracellular loop.\",\n      \"method\": \"Single-particle electron microscopy, peptide array screening, in vitro mutagenesis, binding and gating assays\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — structural EM, mutagenesis, and functional gating assays in same study\",\n      \"pmids\": [\"25186755\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CNIH-2 differentially modulates AMPAR gating depending on TARP isoform: with γ-8 (hippocampal), CNIH-2 slows deactivation, increases cyclothiazide potency and occludes resensitization; with γ-2 (cerebellar), CNIH-2 has minimal kinetic effects but decreases IKA/IGlu ratio.\",\n      \"method\": \"Electrophysiology in recombinant expression systems with defined TARP isoforms, pharmacological profiling\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — systematic electrophysiology across isoforms with clear mechanistic dissection\",\n      \"pmids\": [\"22211840\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CNIH-2 allosterically modifies AMPA receptor pharmacology, conferring partial sensitivity of potentiator binding to displacement by non-competitive antagonists in a manner that depends on the auxiliary subunit composition of the receptor complex.\",\n      \"method\": \"Radioligand binding assays ([3H]-LY450295), autoradiography in brain sections from stargazer and γ-8 KO mice\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — radioligand binding with KO mice, but single lab and primarily pharmacological readout\",\n      \"pmids\": [\"21343286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CNIH-2 and CNIH-3 associate with GluA subunits in the early secretory pathway; during ontogeny, an excess of AMPAR-free CNIH-2/3 exists early postnatally (consistent with ER cargo exporter role) but shifts toward AMPAR-integrated forms during development.\",\n      \"method\": \"Developmental expression profiling, co-immunoprecipitation, subcellular fractionation in rat brain\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — Co-IP and fractionation across developmental timepoints; single lab\",\n      \"pmids\": [\"23403072\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"GSG1L association with AMPARs inhibits CNIH2-induced slowing of receptor kinetics in heterologous cells, defining a competitive or antagonistic relationship between these two auxiliary subunits in modulating AMPAR deactivation and desensitization.\",\n      \"method\": \"Electrophysiology in heterologous cells with co-expression of GSG1L and CNIH2\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional electrophysiology in recombinant system; single lab but clear mechanistic result\",\n      \"pmids\": [\"26932439\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"SAP102-mediated rescue of AMPAR-mediated synaptic transmission requires CNIH-2; knockdown of CNIH-2 abolishes the SAP102-dependent increase in AMPAR EPSC decay time, placing CNIH-2 downstream of SAP102 in regulating synaptic AMPAR kinetics.\",\n      \"method\": \"Cell-restricted molecular replacement of PSD-95 with SAP102, CNIH-2 knockdown, whole-cell electrophysiology\",\n      \"journal\": \"Journal of neurophysiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — epistasis established by genetic replacement strategy with electrophysiological readout; single lab\",\n      \"pmids\": [\"30067114\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CNIH2 (cornichon-like protein/CNIL) facilitates secretion of HB-EGF in a cell culture system, and its perturbation in chick embryos (by truncated CNIH expression or siRNA knockdown) disrupts neural crest cell distribution and cranial nerve development, phenocopying ErbB4 knockout.\",\n      \"method\": \"Cell culture secretion assay, chick embryo dominant-negative overexpression and siRNA knockdown, in situ hybridization\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function in vivo with defined phenotypic readout and cell culture secretion assay; chick ortholog study\",\n      \"pmids\": [\"17229890\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Knockdown of PORCN in hippocampal neurons leads to depletion of TARP γ-8 from AMPAR complexes, demonstrating that PORCN regulates the composition of AMPAR auxiliary subunit assemblies including CNIH-2/3-containing complexes.\",\n      \"method\": \"Immunoprecipitation of AMPAR complexes, PORCN knockdown and conditional KO, electrophysiology\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP and KO with defined biochemical and functional readout; CNIH-2 as part of the complex rather than primary focus\",\n      \"pmids\": [\"26776514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CNIH-2 enhances tetramerization of wild-type and mutant AMPARs, primarily through interactions with the transmembrane domain of the receptor, and promotes surface expression more effectively than TARP γ-2. CNIH-2 enhances both GluA1 and GluA2 tetramerization, whereas CNIH-3 only weakly enhances GluA1 tetramerization.\",\n      \"method\": \"In vitro tetramerization assays, surface expression assays in heterologous cells, mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro assay with mutagenesis; single lab\",\n      \"pmids\": [\"37673338\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Interaction proteomics demonstrates that CNIH-2 co-purifies with highest abundance in GluA1/2 receptor complexes alongside TARP-γ8 and SynDIG4, and also co-purifies strongly with GluA2/3 receptors, revealing subtype-specific AMPAR–auxiliary subunit associations.\",\n      \"method\": \"Interaction proteomics (immunoprecipitation–mass spectrometry) from Gria1 and Gria3 knockout mouse hippocampi\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — MS-based interactome from KO mice; single lab\",\n      \"pmids\": [\"36429079\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CPSF3 promotes CNIH2 expression in esophageal squamous cell carcinoma by inducing use of a proximal poly(A) site in the CNIH2 3'UTR, thereby preventing miR-125a-5p-mediated repression of CNIH2 mRNA. CPSF3-induced tumorigenicity is mediated by CNIH2, as CNIH2 knockdown inhibits ESCC cell proliferation, migration, invasion, and tumor growth in vivo.\",\n      \"method\": \"Iso-Seq and RNA-seq APA analysis, CPSF3 knockdown/overexpression, colony formation/transwell assays, xenograft experiments, luciferase reporter for miRNA binding\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined molecular mechanism (APA/miRNA) and in vivo xenograft; single lab\",\n      \"pmids\": [\"38718887\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CNIH-2 mRNA is locally translated in dendrites, and this local synthesis increases after chemical LTP induction. Local CNIH-2 translation is required for plasma membrane insertion of GluA2-containing (calcium-impermeable) AMPARs but not GluA1-homomeric AMPARs, selectively enabling slow-response AMPAR trafficking after plasticity induction.\",\n      \"method\": \"Dendritic mRNA localization assays, local translation reporters, chemical LTP induction, selective trafficking assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple experimental approaches including local translation inhibition and LTP paradigm; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.02.08.637220\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CNIH2 is a transmembrane auxiliary subunit of hippocampal AMPA receptors that occupies defined positions (A'/C') in the native receptor complex alongside TARP-γ8, where its extended M2 helix pivots toward the pore upon activation to slow AMPAR deactivation and desensitization, reduce desensitization, enhance single-channel conductance and calcium permeability, promote GluA tetramerization and ER-to-surface trafficking in a COPII-dependent manner, and synergize with TARP-γ8 to dictate the subunit composition, kinetics, and pharmacology of synaptic AMPARs in hippocampal neurons; additionally, CNIH2 mRNA is locally translated in dendrites and this local synthesis is selectively required for LTP-induced membrane insertion of GluA2-containing receptors.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CNIH2 is a transmembrane auxiliary subunit of AMPA-type glutamate receptors that modulates receptor assembly, trafficking, gating kinetics, and synaptic transmission in hippocampal neurons. CNIH2 associates with AMPAR complexes in a TARP-γ8-dependent manner, occupying defined positions (A'/C') in the native receptor architecture where its extended M2 helix pivots toward the pore upon activation to slow deactivation and desensitization, enhance single-channel conductance and calcium permeability, and shape synapse-specific EPSC kinetics [PMID:21172611, PMID:34079129, PMID:24853943]. Beyond gating modulation, CNIH2 promotes GluA subunit tetramerization through transmembrane domain interactions and facilitates ER-to-surface receptor trafficking via COPII-dependent export, functioning as both a cargo exporter and a bona fide auxiliary subunit [PMID:22292017, PMID:37673338]. Conditional loss of CNIH2/3 selectively removes GluA1-containing AMPARs from hippocampal synapses, demonstrating a non-redundant role in determining the subunit composition and kinetic identity of synaptic receptor pools [PMID:23522044, PMID:22815494].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Before CNIH2 was linked to AMPA receptors, its ancestral role as a secretory pathway cargo exporter was established: CNIH2 facilitated HB-EGF secretion and its perturbation disrupted neural crest cell migration and cranial nerve patterning in chick embryos, revealing a developmental function through growth factor export.\",\n      \"evidence\": \"Cell culture secretion assay, dominant-negative and siRNA knockdown in chick embryos with phenotypic analysis\",\n      \"pmids\": [\"17229890\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Chick ortholog study; relevance to mammalian CNIH2 function not directly tested\", \"Mechanism of selective cargo recognition for HB-EGF not defined\", \"Relationship to AMPAR biology unknown at this point\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The discovery that CNIH2 physically associates with γ-8-containing AMPAR complexes in hippocampal postsynaptic densities established it as a neuronal AMPAR auxiliary subunit rather than merely an ER export factor; CNIH2 synergized with TARP-γ8 to modulate receptor kinetics and pharmacology, and its protein stability depended on γ-8.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation from PSDs, electrophysiology in recombinant systems and hippocampal neurons, γ-8 knockout mice\",\n      \"pmids\": [\"21172611\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of CNIH2–TARP–AMPAR interaction unknown\", \"Whether CNIH2 reaches the neuronal surface independently of γ-8 was unclear\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Systematic electrophysiological and pharmacological profiling revealed that CNIH2's gating modulation is TARP-isoform-dependent — slowing deactivation and occluding resensitization with γ-8 but having minimal kinetic effects with γ-2 — explaining region-specific AMPAR properties and showing that CNIH2 reduces TARP stoichiometry within receptor complexes.\",\n      \"evidence\": \"Electrophysiology with defined TARP isoforms in recombinant systems, tandem GluA/TARP stoichiometry-constrained constructs, surface biotinylation, radioligand binding with KO mice\",\n      \"pmids\": [\"21543622\", \"22211840\", \"21343286\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of stoichiometric competition between CNIH2 and TARPs at the molecular level unresolved\", \"In vivo consequences of pharmacological modulation not tested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Two key properties of CNIH2 were mechanistically dissected: it cycles between ER and Golgi in a COPII-dependent manner (fulfilling an ancestral cargo export role that GluA subunits commandeer for surface delivery), and it enhances single-channel conductance, calcium permeability, and glutamate sensitivity of both CI- and CP-AMPARs.\",\n      \"evidence\": \"Live-cell imaging of ER-Golgi cycling, COPII export assays, single-channel recordings in heterologous cells\",\n      \"pmids\": [\"22292017\", \"22815494\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How GluA subunits redirect CNIH2 from ER cycling to surface retention not structurally defined\", \"Whether COPII-dependent export is rate-limiting for synaptic AMPAR delivery in vivo unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Conditional knockout of CNIH2/3 in hippocampal neurons demonstrated a non-redundant requirement for surface expression and synaptic transmission of GluA1-containing AMPARs, with loss selectively removing GluA1A2 heteromers and leaving faster-kinetics GluA2A3 receptors — establishing CNIH2/3 as gatekeepers of AMPAR subunit composition at synapses.\",\n      \"evidence\": \"CNIH-2/CNIH-3 conditional knockout mice, whole-cell electrophysiology, surface receptor biochemistry, developmental co-IP\",\n      \"pmids\": [\"23522044\", \"23403072\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CNIH2 and CNIH3 have distinct or fully redundant roles not fully separated\", \"Downstream signaling consequences of altered subunit composition not explored\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"At identified hippocampal synapses, CNIH2 was shown to be the primary determinant of slow EPSC decay: knockdown accelerated mossy fiber–hilar mossy cell EPSCs, and ectopic expression in fast-EPSC interneurons slowed their kinetics, while structural work on CNIH3 identified the extracellular loop and membrane-proximal residues as critical for AMPAR binding and gating modulation.\",\n      \"evidence\": \"Paired whole-cell recordings with shRNA knockdown and viral gain-of-function; single-particle EM, peptide array screening, mutagenesis\",\n      \"pmids\": [\"24853943\", \"25186755\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether all hippocampal synapse types use CNIH2 to set kinetics not surveyed\", \"Precise structural contacts between CNIH2 extracellular loop and AMPAR LBD not resolved at atomic level\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The auxiliary subunit GSG1L was found to antagonize CNIH2-mediated slowing of AMPAR kinetics, revealing a competitive regulatory axis among auxiliary subunits, while PORCN was shown to regulate TARP-γ8 incorporation into AMPAR complexes including those containing CNIH2.\",\n      \"evidence\": \"Electrophysiology with GSG1L/CNIH2 co-expression; PORCN knockdown/KO with co-IP and electrophysiology\",\n      \"pmids\": [\"26932439\", \"26776514\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether GSG1L-CNIH2 competition occurs at the same binding site or allosterically is unknown\", \"In vivo relevance of GSG1L–CNIH2 antagonism at specific synapses not demonstrated\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Cryo-EM structures of native and reconstituted AMPAR complexes revealed the atomic-level architecture: CNIH2 and TARP-γ8 occupy non-equivalent positions (A'/C' and B'/D' respectively) with site-specific lipids, and upon receptor activation CNIH2's uniquely extended M2 helix counter-rotates and pivots toward the pore exit, providing the structural basis for its powerful gating modulation.\",\n      \"evidence\": \"Cryo-EM of native hippocampal AMPARs and reconstituted GluA1-GluA2/γ8/CNIH2 in resting and active states\",\n      \"pmids\": [\"33981040\", \"34079129\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Desensitized-state structure with CNIH2 not resolved\", \"How lipid specificity at CNIH2 vs TARP sites affects function not tested\", \"Structures of complexes with other auxiliary subunit combinations lacking\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"CNIH2 was found to promote AMPAR tetramerization through transmembrane domain interactions more effectively than TARP-γ2, revealing a previously unrecognized role in receptor assembly upstream of ER export.\",\n      \"evidence\": \"In vitro tetramerization assays, surface expression assays, mutagenesis in heterologous cells\",\n      \"pmids\": [\"37673338\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether tetramerization enhancement is rate-limiting for AMPAR biogenesis in neurons not shown\", \"Structural basis of TMD-mediated tetramerization promotion not determined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Outside the nervous system, CNIH2 was implicated in esophageal squamous cell carcinoma tumorigenicity, where CPSF3 promotes CNIH2 expression by inducing proximal poly(A) site usage that evades miR-125a-5p-mediated mRNA repression.\",\n      \"evidence\": \"APA analysis, CPSF3/CNIH2 knockdown and overexpression, xenograft tumor models, luciferase reporters\",\n      \"pmids\": [\"38718887\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether CNIH2's tumorigenic role acts through AMPAR signaling or an AMPAR-independent mechanism is unknown\", \"Single cancer type studied; generalizability not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include: (1) the structural mechanism by which CNIH2 promotes tetramerization through TMD contacts, (2) how local dendritic translation of CNIH2 mRNA selectively enables GluA2-containing AMPAR insertion during LTP, (3) whether CNIH2 functions independently of AMPARs in non-neuronal contexts such as cancer, and (4) how the CNIH2–GSG1L competitive axis is regulated in vivo at specific synapse types.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No desensitized-state cryo-EM structure with CNIH2\", \"Local translation findings from preprint not yet peer-reviewed\", \"No CNIH2-specific knockout (separate from CNIH3) phenotype fully characterized in behavior\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 4, 7, 9, 12]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 3, 8, 16]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 5, 6, 16]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [6, 11]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 1, 4, 7, 9]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [6, 16]},\n      {\"term_id\": \"R-HSA-382551\", \"supporting_discovery_ids\": [0, 4, 5]}\n    ],\n    \"complexes\": [\n      \"AMPAR-TARP-γ8-CNIH2 complex\",\n      \"GluA1-GluA2/γ8/CNIH2 complex\",\n      \"GluA2-GluA3/γ8/CNIH2 complex\"\n    ],\n    \"partners\": [\n      \"GRIA1\",\n      \"GRIA2\",\n      \"GRIA3\",\n      \"CACNG8\",\n      \"SAP102\",\n      \"GSG1L\",\n      \"CNIH3\",\n      \"PORCN\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}