{"gene":"CTNND2","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":1999,"finding":"NPRAP/delta-catenin (CTNND2) was identified as a constituent of adherens junction plaques at the outer limiting zone (OLZ) of the retina, where it co-localizes with N-cadherin, alpha- and beta-catenin, p120, vinculin, symplekin, ZO-1, and plakophilin 2, but not plakoglobin, defining a novel type of adhering junction.","method":"Immunolocalization techniques in retinal tissue sections","journal":"Experimental Cell Research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunolocalization with multiple co-detected proteins in defined junction, single study but multiple protein markers validated","pmids":["10413599"],"is_preprint":false},{"year":2000,"finding":"Delta-catenin (CTNND2) was originally discovered as a binding partner of presenilin-1 and maps to chromosome 5p15.2; hemizygous loss correlates with severe mental retardation in cri-du-chat syndrome, consistent with a neuronal-specific role in cell motility during early development.","method":"Genomic mapping, breakpoint characterization in patients with 5p deletions, genotype-phenotype correlation","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — genetic mapping and patient breakpoint analysis with phenotypic correlation, no in vitro reconstitution of the presenilin-1 interaction reported in this abstract","pmids":["10673328"],"is_preprint":false},{"year":2004,"finding":"Delta-catenin/NPRAP directly interacts with sphingosine kinase 1 (SPHK1) via its seventh-to-tenth armadillo repeats, co-localizes with SPHK1 in rat hippocampal neurons, stimulates SPHK1 enzymatic activity in a dose-dependent manner in a purified system, and SPHK1 inhibition abolishes delta-catenin-induced cell motility in MDCK cells.","method":"Yeast two-hybrid screening, co-immunoprecipitation, co-localization in neurons, in vitro purified kinase activity assay, pharmacological inhibition of SPHK1","journal":"The Biochemical Journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstituted kinase activation, domain mapping by co-IP, neuronal co-localization, and functional rescue/inhibition in cells; multiple orthogonal methods in single study","pmids":["15193146"],"is_preprint":false},{"year":2008,"finding":"A somatic point mutation (-9 G>A) in the 5'-UTR of the delta-catenin (CTNND2) gene, found in prostate cancer but not adjacent benign tissue, increases delta-catenin expression by promoting translation (not transcription), as shown by chimeric luciferase reporter assays.","method":"SSCP analysis, laser capture microdissection + PCR, chimeric luciferase reporter assays","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay with mutagenesis controls, LCM confirmation of somatic mutation, distinguishes transcriptional vs translational effect; single lab","pmids":["18978817"],"is_preprint":false},{"year":2010,"finding":"Delta-catenin/NPRAP (CTNND2) participates in the GSK-3beta destruction complex in neurons: it co-localizes and co-immunoprecipitates with GSK-3beta, beta-catenin, and APC; GSK-3beta inhibition increases delta-catenin protein levels; delta-catenin overexpression enhances GSK-3beta–beta-catenin interaction and promotes beta-catenin ubiquitination and turnover via proteasomal degradation.","method":"Co-immunoprecipitation, immunofluorescence, cycloheximide chase, proteasome inhibitor treatment, GSK-3beta pharmacological inhibition, overexpression in primary cortical neurons and PC12 cells","journal":"Journal of Neuroscience Research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP, multiple pharmacological and biochemical methods, single lab","pmids":["20623542"],"is_preprint":false},{"year":2010,"finding":"Hes1 (human homolog of Drosophila Hairy/enhancer of split) directly binds E-boxes on the delta-catenin (CTNND2) promoter and represses delta-catenin expression in cooperation with the activating transcription factor E2F1; suppression of Hes1 by gamma-secretase inhibitors or siRNA increases delta-catenin expression.","method":"Delta-catenin promoter-luciferase reporter assay, chromatin binding (E-box), siRNA knockdown, gamma-secretase inhibitors, cell line analysis","journal":"Molecular Cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reporter assay with E-box binding, siRNA and pharmacological perturbation, single lab","pmids":["21106062"],"is_preprint":false},{"year":2011,"finding":"NPRAP/delta-catenin (CTNND2) undergoes nuclear translocation and regulates gene expression in a nuclear-localization-dependent manner, including upregulation of BCHE (linked to Alzheimer's disease), as demonstrated by overexpression, microarray, and localization experiments.","method":"Overexpression, microarray gene expression profiling, nuclear translocation assay","journal":"Journal of Alzheimer's Disease","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-overexpression + microarray study, no mutagenesis of nuclear localization signals reported in abstract","pmids":["21811021"],"is_preprint":false},{"year":2011,"finding":"NPRAP/delta-catenin (CTNND2) directly interacts with dynamin 2 (and also dynamin 1) as identified by co-immunoprecipitation from human SH-SY5Y cells followed by mass spectrometry, with co-localization confirmed in vivo; additional novel interactors include neurofilament alpha-internexin and IRF2 binding factors.","method":"Co-immunoprecipitation from SH-SY5Y cells, mass spectrometry, co-localization","journal":"PLoS ONE","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — reciprocal validation of dynamin 2 interaction by co-IP and co-localization, mass spectrometry identification, single lab","pmids":["22022388"],"is_preprint":false},{"year":2014,"finding":"Morpholino knockdown of ctnnd2 in zebrafish embryos causes misplacement of a subpopulation of forebrain neurons between the diencephalon and telencephalon, demonstrating a direct role for CTNND2 in neuronal migration in vivo.","method":"Morpholino knockdown in zebrafish, analysis of neuronal position in forebrain","journal":"Journal of Medical Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo loss-of-function with specific cellular phenotype (neuronal misplacement), single lab","pmids":["25473103"],"is_preprint":false},{"year":2017,"finding":"A missense mutation p.Glu1044Lys in CTNND2 causes familial cortical myoclonic tremor and epilepsy (FCMTE); knockdown of Ctnnd2 in cortical mouse neurons increases neurite outgrowth, rescued by wild-type but not mutant CTNND2, mirroring morphological abnormalities observed in postmortem FCMTE patient Purkinje cells.","method":"Exome sequencing, shRNA knockdown in cortical mouse neurons, rescue with wild-type vs. mutant overexpression, postmortem brain morphology analysis","journal":"Neurology","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with specific phenotypic readout, mutant-specific rescue failure, corroborated by human postmortem pathology; multiple orthogonal approaches","pmids":["29127138"],"is_preprint":false},{"year":2021,"finding":"Ctnnd2 knockout mice show decreased hippocampal Rictor (mTORC2 component) expression, reduced actin polymerization, and decreased postsynaptic spine density in CA1 neurons; shRNA-mediated Rictor knockdown exacerbates spatial learning/memory deficits in both KO and wild-type mice, implicating the CTNND2–Rictor–mTORC2 axis in synaptic plasticity and spatial cognition.","method":"Ctnnd2 knockout mouse (exon 2 deletion), Morris water maze, Golgi staining, shRNA hippocampal injection, Western blotting","journal":"Frontiers in Bioscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO with defined synaptic phenotype plus epistasis via Rictor shRNA, single lab","pmids":["34455763"],"is_preprint":false},{"year":2024,"finding":"CTNND2 is a major synaptic partner of SRGAP2; it slows synaptic maturation and promotes neuronal integrity during postnatal development, moderates neuronal excitation/excitability, and supports adult synapse maintenance. CTNND2 deficiency causes synaptic loss of SYNGAP1, and the human-specific protein SRGAP2C enhances CTNND2 synaptic accumulation in human neurons, linking CTNND2 regulation to synaptic neoteny.","method":"Co-immunoprecipitation, synaptic fractionation, knockdown/knockout with synaptic phenotyping, human neuron overexpression of SRGAP2C","journal":"Cell Reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP identifying SRGAP2 partnership, multiple loss-of-function cellular phenotypes, human neuron gain-of-function, and SYNGAP1 downstream effect; multiple orthogonal methods","pmids":["39352808"],"is_preprint":false},{"year":2025,"finding":"TMEM97 negatively regulates CTNND2 protein levels in retinal pigment epithelial (RPE) cells; CTNND2 in turn promotes ADAM10 expression, sustaining both E-cadherin and N-cadherin levels and driving partial epithelial-mesenchymal transition (pEMT) in RPE cells.","method":"TMEM97 knockout in ARPE19 cells, subretinal lentiviral re-expression, integrated proteomics, transcriptomics, immunoblotting","journal":"Molecular Therapy: Nucleic Acids","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO plus rescue with multi-omic validation, mechanistic pathway defined via CTNND2-ADAM10 axis; single lab","pmids":["39995975"],"is_preprint":false},{"year":2025,"finding":"Loss-of-function variants in CTNND2 impair early neurogenesis in patient-derived neural stem cells, causing aberrant neural rosette formation; transcriptomic profiling reveals dysregulated WNT signaling, and pharmacological WNT pathway modulation partially rescues these defects, establishing delta-catenin as a regulator of WNT signaling during early neural development.","method":"Patient-derived neural stem cells, CRISPR-Cas9 CTNND2 knockout lines, neural differentiation, transcriptomic profiling, cerebral organoid development, WNT pathway modulation rescue experiment","journal":"Research Square (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple cell line models plus rescue experiment; preprint, not yet peer-reviewed","pmids":["41502569"],"is_preprint":true},{"year":2025,"finding":"Delta-catenin (CTNND2) haploinsufficiency (heterozygous KO or G34S missense) in mice reduces synaptic delta-catenin and AMPA receptor levels in brain extracts and disrupts social behavior and fear learning; homozygous KO previously established that delta-catenin anchors AMPA receptors at excitatory synapses to regulate glutamatergic activity.","method":"Heterozygous delta-catenin KO and G34S knock-in mice, multiple behavioral assays (social interaction, contextual fear conditioning, open field), biochemical assay of synaptic fractions","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — haploinsufficiency model with defined synaptic biochemical phenotype and multiple behavioral readouts; preprint, single lab","pmids":[],"is_preprint":true}],"current_model":"CTNND2 (delta-catenin/NPRAP) is a brain-enriched armadillo-repeat protein that functions at excitatory synapses as an anchor for AMPA receptors and a partner of SRGAP2, slowing synaptic maturation and supporting synapse maintenance (partly via SYNGAP1 retention); it activates sphingosine kinase 1 through its armadillo repeats to promote cell motility; it participates in the GSK-3beta destruction complex to facilitate beta-catenin ubiquitination and turnover; it undergoes nuclear translocation to regulate gene expression; its transcription is activated by E2F1 and repressed by Hes1; and in RPE cells it promotes partial EMT via ADAM10 regulation downstream of TMEM97, while loss-of-function disrupts neuronal migration, dendritic spine density, and WNT signaling during early neurogenesis."},"narrative":{"mechanistic_narrative":"CTNND2 (delta-catenin/NPRAP) is a brain-enriched armadillo-repeat catenin that organizes excitatory synapses and shapes neuronal morphogenesis during cortical development [PMID:39352808, PMID:29127138]. At the synapse it is a major partner of SRGAP2, where it slows synaptic maturation, supports adult synapse maintenance, and is required for retention of SYNGAP1; the human-specific protein SRGAP2C enhances its synaptic accumulation, tying CTNND2 to synaptic neoteny [PMID:39352808]. It anchors AMPA receptors at excitatory synapses to regulate glutamatergic activity, and supports postsynaptic spine density and actin polymerization through an mTORC2 (Rictor) axis [PMID:34455763]. Beyond the synapse, CTNND2 was first identified as a constituent of N-cadherin–based adhering junctions in the retina, associating with alpha-/beta-catenin, p120, and other junctional proteins [PMID:10413599]. It directly binds and stimulates sphingosine kinase 1 (SPHK1) via its seventh-to-tenth armadillo repeats to drive cell motility [PMID:15193146], and participates in a GSK-3beta destruction complex with beta-catenin and APC to promote beta-catenin ubiquitination and turnover [PMID:20623542]. CTNND2 expression is transcriptionally activated by E2F1 and repressed by Hes1 binding to promoter E-boxes [PMID:21106062]. Loss-of-function disrupts neuronal migration in vivo [PMID:25473103] and impairs early neurogenesis with dysregulated WNT signaling [PMID:41502569]. A missense mutation (p.Glu1044Lys) causes familial cortical myoclonic tremor and epilepsy, with mutant protein failing to rescue the neurite-outgrowth phenotype of Ctnnd2 knockdown [PMID:29127138], and hemizygous loss at 5p15.2 correlates with the neurodevelopmental features of cri-du-chat syndrome [PMID:10673328].","teleology":[{"year":1999,"claim":"Establishing where CTNND2 acts, it was localized to a novel N-cadherin–based adhering junction in the retina, defining it as a junctional catenin partner.","evidence":"Immunolocalization in retinal tissue sections with multiple co-detected junctional markers","pmids":["10413599"],"confidence":"Medium","gaps":["No functional consequence of junctional localization tested","Direct binding partners within the junction not biochemically mapped"]},{"year":2000,"claim":"Linking CTNND2 to disease, genomic mapping to 5p15.2 and breakpoint analysis tied hemizygous loss to the neurodevelopmental features of cri-du-chat syndrome and identified presenilin-1 as a binding partner.","evidence":"Genomic mapping and patient breakpoint characterization with genotype-phenotype correlation","pmids":["10673328"],"confidence":"Medium","gaps":["Presenilin-1 interaction not reconstituted in vitro","Causality of CTNND2 loss vs. other 5p genes not isolated"]},{"year":2004,"claim":"Defining a motility mechanism, CTNND2 was shown to directly bind and activate SPHK1 through specific armadillo repeats, with kinase activity required for CTNND2-induced cell motility.","evidence":"Yeast two-hybrid, co-IP domain mapping, purified kinase activation assay, and pharmacological SPHK1 inhibition in MDCK cells","pmids":["15193146"],"confidence":"High","gaps":["Mechanism of SPHK1 activation not structurally resolved","Relevance to neuronal motility not directly tested"]},{"year":2008,"claim":"Addressing how CTNND2 is dysregulated in cancer, a somatic 5'-UTR mutation in prostate cancer was found to raise delta-catenin levels translationally rather than transcriptionally.","evidence":"Laser capture microdissection, SSCP, and chimeric luciferase reporter assays","pmids":["18978817"],"confidence":"Medium","gaps":["Downstream oncogenic consequence of elevated CTNND2 not established","Single-lab finding"]},{"year":2010,"claim":"Two studies defined CTNND2's role in WNT/catenin homeostasis and its transcriptional control: it joins a GSK-3beta destruction complex promoting beta-catenin turnover, and its expression is activated by E2F1 yet repressed by Hes1.","evidence":"Reciprocal co-IP, cycloheximide chase, proteasome/GSK-3beta inhibition in neurons; promoter-luciferase and E-box binding with siRNA/gamma-secretase perturbation","pmids":["20623542","21106062"],"confidence":"Medium","gaps":["Direct enzymatic role of CTNND2 within the destruction complex unclear","Physiological context coupling transcriptional control to synaptic function not defined"]},{"year":2011,"claim":"Probing a nuclear function, CTNND2 was shown to translocate to the nucleus and alter gene expression, and to physically associate with dynamin 2 and other neuronal proteins.","evidence":"Overexpression, microarray, nuclear translocation assay; co-IP/mass spectrometry from SH-SY5Y cells with co-localization","pmids":["21811021","22022388"],"confidence":"Medium","gaps":["Nuclear localization signal not mapped by mutagenesis","Functional significance of dynamin interaction untested"]},{"year":2014,"claim":"Demonstrating an in vivo developmental role, ctnnd2 knockdown in zebrafish caused misplacement of forebrain neurons, establishing a direct requirement in neuronal migration.","evidence":"Morpholino knockdown in zebrafish embryos with forebrain neuron position analysis","pmids":["25473103"],"confidence":"Medium","gaps":["Molecular pathway driving migration defect not defined","Morpholino specificity not orthogonally confirmed"]},{"year":2017,"claim":"Connecting CTNND2 to a Mendelian disease, a p.Glu1044Lys mutation was shown to cause FCMTE, with the mutant failing to rescue the neurite-outgrowth phenotype of knockdown.","evidence":"Exome sequencing, shRNA knockdown with wild-type vs. mutant rescue, and postmortem Purkinje cell morphology","pmids":["29127138"],"confidence":"High","gaps":["Biochemical defect conferred by E1044K not defined","Mechanism linking neurite changes to tremor/epilepsy unresolved"]},{"year":2021,"claim":"Defining a synaptic plasticity mechanism, Ctnnd2 knockout reduced hippocampal Rictor, actin polymerization, and spine density, placing CTNND2 upstream of an mTORC2 axis controlling spatial cognition.","evidence":"Ctnnd2 KO mice, Morris water maze, Golgi staining, and Rictor shRNA epistasis","pmids":["34455763"],"confidence":"Medium","gaps":["Direct biochemical link between CTNND2 and Rictor not shown","Single-lab finding"]},{"year":2024,"claim":"Identifying CTNND2's principal synaptic role, it was shown to partner SRGAP2 to slow synaptic maturation and maintain synapses, retain SYNGAP1, and be amplified at human synapses by SRGAP2C.","evidence":"Reciprocal co-IP, synaptic fractionation, loss-of-function phenotyping, and SRGAP2C gain-of-function in human neurons","pmids":["39352808"],"confidence":"High","gaps":["Structural basis of SRGAP2–CTNND2 interaction unresolved","Mechanism by which CTNND2 loss depletes SYNGAP1 not detailed"]},{"year":2025,"claim":"Extending CTNND2 to epithelial biology, TMEM97 was shown to suppress CTNND2 levels, with CTNND2 driving ADAM10 expression and partial EMT in retinal pigment epithelial cells.","evidence":"TMEM97 KO and re-expression in ARPE19 cells with integrated proteomics and transcriptomics","pmids":["39995975"],"confidence":"Medium","gaps":["Mechanism of TMEM97-dependent CTNND2 regulation unknown","Relevance to in vivo RPE pathology untested"]},{"year":2025,"claim":"Two models refined CTNND2's developmental and synaptic roles: loss-of-function disrupted early neurogenesis via dysregulated WNT signaling, and haploinsufficiency reduced synaptic AMPA receptor anchoring with social and fear-learning deficits.","evidence":"Patient-derived NSC/CRISPR KO lines with WNT modulation rescue (preprint); heterozygous KO and G34S knock-in mice with synaptic biochemistry and behavior (preprint)","pmids":["41502569"],"confidence":"Medium","gaps":["Both findings from preprints not yet peer-reviewed","Direct mechanism coupling CTNND2 to WNT pathway components not defined"]},{"year":null,"claim":"How CTNND2's diverse activities—synaptic AMPA receptor anchoring, beta-catenin/WNT regulation, and SPHK1-driven motility—are coordinated within a single molecular framework remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model integrating armadillo-repeat partner binding","Whether nuclear and synaptic pools represent distinct functional states is unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[11,14]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[11,14]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,11]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[4,7]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,13]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[11,14]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8,13]}],"complexes":["GSK-3beta/beta-catenin/APC destruction complex"],"partners":["SRGAP2","SPHK1","GSK3B","CTNNB1","APC","DNM2","PSEN1","CDH2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9UQB3","full_name":"Catenin delta-2","aliases":["Delta-catenin","GT24","Neural plakophilin-related ARM-repeat protein","NPRAP","Neurojungin"],"length_aa":1225,"mass_kda":132.7,"function":"Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules","subcellular_location":"Nucleus; Cell junction, adherens junction; Cell projection, dendrite; Perikaryon","url":"https://www.uniprot.org/uniprotkb/Q9UQB3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CTNND2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CTNND2","total_profiled":1310},"omim":[{"mim_id":"614453","title":"LEUCINE-RICH REPEAT-CONTAINING PROTEIN 7; LRRC7","url":"https://www.omim.org/entry/614453"},{"mim_id":"613608","title":"EPILEPSY, FAMILIAL ADULT MYOCLONIC, 3; FAME3","url":"https://www.omim.org/entry/613608"},{"mim_id":"613114","title":"RETICULOPHAGY REGULATOR 1; RETREG1","url":"https://www.omim.org/entry/613114"},{"mim_id":"610697","title":"PDZ DOMAIN-CONTAINING 2; PDZD2","url":"https://www.omim.org/entry/610697"},{"mim_id":"606382","title":"MEMBRANE-ASSOCIATED GUANYLATE KINASE, WW AND PDZ DOMAINS-CONTAINING, 2; MAGI2","url":"https://www.omim.org/entry/606382"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cell Junctions","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"brain","ntpm":72.2}],"url":"https://www.proteinatlas.org/search/CTNND2"},"hgnc":{"alias_symbol":["NPRAP","GT24"],"prev_symbol":[]},"alphafold":{"accession":"Q9UQB3","domains":[{"cath_id":"1.25.10.10","chopping":"549-666","consensus_level":"medium","plddt":96.6729,"start":549,"end":666},{"cath_id":"1.25.10.10","chopping":"672-694_706-783_836-876","consensus_level":"medium","plddt":92.9153,"start":672,"end":876},{"cath_id":"1.20.1050","chopping":"922-945_952-1034","consensus_level":"high","plddt":91.9536,"start":922,"end":1034}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UQB3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UQB3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9UQB3-F1-predicted_aligned_error_v6.png","plddt_mean":58.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CTNND2","jax_strain_url":"https://www.jax.org/strain/search?query=CTNND2"},"sequence":{"accession":"Q9UQB3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9UQB3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9UQB3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9UQB3"}},"corpus_meta":[{"pmid":"10673328","id":"PMC_10673328","title":"Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome.","date":"2000","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10673328","citation_count":136,"is_preprint":false},{"pmid":"21095009","id":"PMC_21095009","title":"Genome-wide association studies reveal genetic variants in CTNND2 for high myopia in Singapore Chinese.","date":"2010","source":"Ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/21095009","citation_count":109,"is_preprint":false},{"pmid":"10413599","id":"PMC_10413599","title":"The arm-repeat protein NPRAP (neurojungin) is a constituent of the plaques of the outer limiting zone in the retina, defining a novel type of adhering junction.","date":"1999","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/10413599","citation_count":75,"is_preprint":false},{"pmid":"24256404","id":"PMC_24256404","title":"Further confirmation of the association between anxiety and CTNND2: replication in 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hemizygous loss correlates with severe mental retardation in cri-du-chat syndrome, consistent with a neuronal-specific role in cell motility during early development.\",\n      \"method\": \"Genomic mapping, breakpoint characterization in patients with 5p deletions, genotype-phenotype correlation\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — genetic mapping and patient breakpoint analysis with phenotypic correlation, no in vitro reconstitution of the presenilin-1 interaction reported in this abstract\",\n      \"pmids\": [\"10673328\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Delta-catenin/NPRAP directly interacts with sphingosine kinase 1 (SPHK1) via its seventh-to-tenth armadillo repeats, co-localizes with SPHK1 in rat hippocampal neurons, stimulates SPHK1 enzymatic activity in a dose-dependent manner in a purified system, and SPHK1 inhibition abolishes delta-catenin-induced cell motility in MDCK cells.\",\n      \"method\": \"Yeast two-hybrid screening, co-immunoprecipitation, co-localization in neurons, in vitro purified kinase activity assay, pharmacological inhibition of SPHK1\",\n      \"journal\": \"The Biochemical Journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstituted kinase activation, domain mapping by co-IP, neuronal co-localization, and functional rescue/inhibition in cells; multiple orthogonal methods in single study\",\n      \"pmids\": [\"15193146\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"A somatic point mutation (-9 G>A) in the 5'-UTR of the delta-catenin (CTNND2) gene, found in prostate cancer but not adjacent benign tissue, increases delta-catenin expression by promoting translation (not transcription), as shown by chimeric luciferase reporter assays.\",\n      \"method\": \"SSCP analysis, laser capture microdissection + PCR, chimeric luciferase reporter assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay with mutagenesis controls, LCM confirmation of somatic mutation, distinguishes transcriptional vs translational effect; single lab\",\n      \"pmids\": [\"18978817\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Delta-catenin/NPRAP (CTNND2) participates in the GSK-3beta destruction complex in neurons: it co-localizes and co-immunoprecipitates with GSK-3beta, beta-catenin, and APC; GSK-3beta inhibition increases delta-catenin protein levels; delta-catenin overexpression enhances GSK-3beta–beta-catenin interaction and promotes beta-catenin ubiquitination and turnover via proteasomal degradation.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, cycloheximide chase, proteasome inhibitor treatment, GSK-3beta pharmacological inhibition, overexpression in primary cortical neurons and PC12 cells\",\n      \"journal\": \"Journal of Neuroscience Research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP, multiple pharmacological and biochemical methods, single lab\",\n      \"pmids\": [\"20623542\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Hes1 (human homolog of Drosophila Hairy/enhancer of split) directly binds E-boxes on the delta-catenin (CTNND2) promoter and represses delta-catenin expression in cooperation with the activating transcription factor E2F1; suppression of Hes1 by gamma-secretase inhibitors or siRNA increases delta-catenin expression.\",\n      \"method\": \"Delta-catenin promoter-luciferase reporter assay, chromatin binding (E-box), siRNA knockdown, gamma-secretase inhibitors, cell line analysis\",\n      \"journal\": \"Molecular Cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reporter assay with E-box binding, siRNA and pharmacological perturbation, single lab\",\n      \"pmids\": [\"21106062\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NPRAP/delta-catenin (CTNND2) undergoes nuclear translocation and regulates gene expression in a nuclear-localization-dependent manner, including upregulation of BCHE (linked to Alzheimer's disease), as demonstrated by overexpression, microarray, and localization experiments.\",\n      \"method\": \"Overexpression, microarray gene expression profiling, nuclear translocation assay\",\n      \"journal\": \"Journal of Alzheimer's Disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-overexpression + microarray study, no mutagenesis of nuclear localization signals reported in abstract\",\n      \"pmids\": [\"21811021\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NPRAP/delta-catenin (CTNND2) directly interacts with dynamin 2 (and also dynamin 1) as identified by co-immunoprecipitation from human SH-SY5Y cells followed by mass spectrometry, with co-localization confirmed in vivo; additional novel interactors include neurofilament alpha-internexin and IRF2 binding factors.\",\n      \"method\": \"Co-immunoprecipitation from SH-SY5Y cells, mass spectrometry, co-localization\",\n      \"journal\": \"PLoS ONE\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — reciprocal validation of dynamin 2 interaction by co-IP and co-localization, mass spectrometry identification, single lab\",\n      \"pmids\": [\"22022388\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Morpholino knockdown of ctnnd2 in zebrafish embryos causes misplacement of a subpopulation of forebrain neurons between the diencephalon and telencephalon, demonstrating a direct role for CTNND2 in neuronal migration in vivo.\",\n      \"method\": \"Morpholino knockdown in zebrafish, analysis of neuronal position in forebrain\",\n      \"journal\": \"Journal of Medical Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo loss-of-function with specific cellular phenotype (neuronal misplacement), single lab\",\n      \"pmids\": [\"25473103\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"A missense mutation p.Glu1044Lys in CTNND2 causes familial cortical myoclonic tremor and epilepsy (FCMTE); knockdown of Ctnnd2 in cortical mouse neurons increases neurite outgrowth, rescued by wild-type but not mutant CTNND2, mirroring morphological abnormalities observed in postmortem FCMTE patient Purkinje cells.\",\n      \"method\": \"Exome sequencing, shRNA knockdown in cortical mouse neurons, rescue with wild-type vs. mutant overexpression, postmortem brain morphology analysis\",\n      \"journal\": \"Neurology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with specific phenotypic readout, mutant-specific rescue failure, corroborated by human postmortem pathology; multiple orthogonal approaches\",\n      \"pmids\": [\"29127138\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Ctnnd2 knockout mice show decreased hippocampal Rictor (mTORC2 component) expression, reduced actin polymerization, and decreased postsynaptic spine density in CA1 neurons; shRNA-mediated Rictor knockdown exacerbates spatial learning/memory deficits in both KO and wild-type mice, implicating the CTNND2–Rictor–mTORC2 axis in synaptic plasticity and spatial cognition.\",\n      \"method\": \"Ctnnd2 knockout mouse (exon 2 deletion), Morris water maze, Golgi staining, shRNA hippocampal injection, Western blotting\",\n      \"journal\": \"Frontiers in Bioscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO with defined synaptic phenotype plus epistasis via Rictor shRNA, single lab\",\n      \"pmids\": [\"34455763\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CTNND2 is a major synaptic partner of SRGAP2; it slows synaptic maturation and promotes neuronal integrity during postnatal development, moderates neuronal excitation/excitability, and supports adult synapse maintenance. CTNND2 deficiency causes synaptic loss of SYNGAP1, and the human-specific protein SRGAP2C enhances CTNND2 synaptic accumulation in human neurons, linking CTNND2 regulation to synaptic neoteny.\",\n      \"method\": \"Co-immunoprecipitation, synaptic fractionation, knockdown/knockout with synaptic phenotyping, human neuron overexpression of SRGAP2C\",\n      \"journal\": \"Cell Reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP identifying SRGAP2 partnership, multiple loss-of-function cellular phenotypes, human neuron gain-of-function, and SYNGAP1 downstream effect; multiple orthogonal methods\",\n      \"pmids\": [\"39352808\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TMEM97 negatively regulates CTNND2 protein levels in retinal pigment epithelial (RPE) cells; CTNND2 in turn promotes ADAM10 expression, sustaining both E-cadherin and N-cadherin levels and driving partial epithelial-mesenchymal transition (pEMT) in RPE cells.\",\n      \"method\": \"TMEM97 knockout in ARPE19 cells, subretinal lentiviral re-expression, integrated proteomics, transcriptomics, immunoblotting\",\n      \"journal\": \"Molecular Therapy: Nucleic Acids\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO plus rescue with multi-omic validation, mechanistic pathway defined via CTNND2-ADAM10 axis; single lab\",\n      \"pmids\": [\"39995975\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss-of-function variants in CTNND2 impair early neurogenesis in patient-derived neural stem cells, causing aberrant neural rosette formation; transcriptomic profiling reveals dysregulated WNT signaling, and pharmacological WNT pathway modulation partially rescues these defects, establishing delta-catenin as a regulator of WNT signaling during early neural development.\",\n      \"method\": \"Patient-derived neural stem cells, CRISPR-Cas9 CTNND2 knockout lines, neural differentiation, transcriptomic profiling, cerebral organoid development, WNT pathway modulation rescue experiment\",\n      \"journal\": \"Research Square (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple cell line models plus rescue experiment; preprint, not yet peer-reviewed\",\n      \"pmids\": [\"41502569\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Delta-catenin (CTNND2) haploinsufficiency (heterozygous KO or G34S missense) in mice reduces synaptic delta-catenin and AMPA receptor levels in brain extracts and disrupts social behavior and fear learning; homozygous KO previously established that delta-catenin anchors AMPA receptors at excitatory synapses to regulate glutamatergic activity.\",\n      \"method\": \"Heterozygous delta-catenin KO and G34S knock-in mice, multiple behavioral assays (social interaction, contextual fear conditioning, open field), biochemical assay of synaptic fractions\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — haploinsufficiency model with defined synaptic biochemical phenotype and multiple behavioral readouts; preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CTNND2 (delta-catenin/NPRAP) is a brain-enriched armadillo-repeat protein that functions at excitatory synapses as an anchor for AMPA receptors and a partner of SRGAP2, slowing synaptic maturation and supporting synapse maintenance (partly via SYNGAP1 retention); it activates sphingosine kinase 1 through its armadillo repeats to promote cell motility; it participates in the GSK-3beta destruction complex to facilitate beta-catenin ubiquitination and turnover; it undergoes nuclear translocation to regulate gene expression; its transcription is activated by E2F1 and repressed by Hes1; and in RPE cells it promotes partial EMT via ADAM10 regulation downstream of TMEM97, while loss-of-function disrupts neuronal migration, dendritic spine density, and WNT signaling during early neurogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CTNND2 (delta-catenin/NPRAP) is a brain-enriched armadillo-repeat catenin that organizes excitatory synapses and shapes neuronal morphogenesis during cortical development [#11, #9]. At the synapse it is a major partner of SRGAP2, where it slows synaptic maturation, supports adult synapse maintenance, and is required for retention of SYNGAP1; the human-specific protein SRGAP2C enhances its synaptic accumulation, tying CTNND2 to synaptic neoteny [#11]. It anchors AMPA receptors at excitatory synapses to regulate glutamatergic activity, and supports postsynaptic spine density and actin polymerization through an mTORC2 (Rictor) axis [#10]. Beyond the synapse, CTNND2 was first identified as a constituent of N-cadherin\\u2013based adhering junctions in the retina, associating with alpha-/beta-catenin, p120, and other junctional proteins [#0]. It directly binds and stimulates sphingosine kinase 1 (SPHK1) via its seventh-to-tenth armadillo repeats to drive cell motility [#2], and participates in a GSK-3beta destruction complex with beta-catenin and APC to promote beta-catenin ubiquitination and turnover [#4]. CTNND2 expression is transcriptionally activated by E2F1 and repressed by Hes1 binding to promoter E-boxes [#5]. Loss-of-function disrupts neuronal migration in vivo [#8] and impairs early neurogenesis with dysregulated WNT signaling [#13]. A missense mutation (p.Glu1044Lys) causes familial cortical myoclonic tremor and epilepsy, with mutant protein failing to rescue the neurite-outgrowth phenotype of Ctnnd2 knockdown [#9], and hemizygous loss at 5p15.2 correlates with the neurodevelopmental features of cri-du-chat syndrome [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Establishing where CTNND2 acts, it was localized to a novel N-cadherin\\u2013based adhering junction in the retina, defining it as a junctional catenin partner.\",\n      \"evidence\": \"Immunolocalization in retinal tissue sections with multiple co-detected junctional markers\",\n      \"pmids\": [\"10413599\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional consequence of junctional localization tested\", \"Direct binding partners within the junction not biochemically mapped\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Linking CTNND2 to disease, genomic mapping to 5p15.2 and breakpoint analysis tied hemizygous loss to the neurodevelopmental features of cri-du-chat syndrome and identified presenilin-1 as a binding partner.\",\n      \"evidence\": \"Genomic mapping and patient breakpoint characterization with genotype-phenotype correlation\",\n      \"pmids\": [\"10673328\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Presenilin-1 interaction not reconstituted in vitro\", \"Causality of CTNND2 loss vs. other 5p genes not isolated\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Defining a motility mechanism, CTNND2 was shown to directly bind and activate SPHK1 through specific armadillo repeats, with kinase activity required for CTNND2-induced cell motility.\",\n      \"evidence\": \"Yeast two-hybrid, co-IP domain mapping, purified kinase activation assay, and pharmacological SPHK1 inhibition in MDCK cells\",\n      \"pmids\": [\"15193146\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of SPHK1 activation not structurally resolved\", \"Relevance to neuronal motility not directly tested\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Addressing how CTNND2 is dysregulated in cancer, a somatic 5'-UTR mutation in prostate cancer was found to raise delta-catenin levels translationally rather than transcriptionally.\",\n      \"evidence\": \"Laser capture microdissection, SSCP, and chimeric luciferase reporter assays\",\n      \"pmids\": [\"18978817\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream oncogenic consequence of elevated CTNND2 not established\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Two studies defined CTNND2's role in WNT/catenin homeostasis and its transcriptional control: it joins a GSK-3beta destruction complex promoting beta-catenin turnover, and its expression is activated by E2F1 yet repressed by Hes1.\",\n      \"evidence\": \"Reciprocal co-IP, cycloheximide chase, proteasome/GSK-3beta inhibition in neurons; promoter-luciferase and E-box binding with siRNA/gamma-secretase perturbation\",\n      \"pmids\": [\"20623542\", \"21106062\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct enzymatic role of CTNND2 within the destruction complex unclear\", \"Physiological context coupling transcriptional control to synaptic function not defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Probing a nuclear function, CTNND2 was shown to translocate to the nucleus and alter gene expression, and to physically associate with dynamin 2 and other neuronal proteins.\",\n      \"evidence\": \"Overexpression, microarray, nuclear translocation assay; co-IP/mass spectrometry from SH-SY5Y cells with co-localization\",\n      \"pmids\": [\"21811021\", \"22022388\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Nuclear localization signal not mapped by mutagenesis\", \"Functional significance of dynamin interaction untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating an in vivo developmental role, ctnnd2 knockdown in zebrafish caused misplacement of forebrain neurons, establishing a direct requirement in neuronal migration.\",\n      \"evidence\": \"Morpholino knockdown in zebrafish embryos with forebrain neuron position analysis\",\n      \"pmids\": [\"25473103\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular pathway driving migration defect not defined\", \"Morpholino specificity not orthogonally confirmed\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connecting CTNND2 to a Mendelian disease, a p.Glu1044Lys mutation was shown to cause FCMTE, with the mutant failing to rescue the neurite-outgrowth phenotype of knockdown.\",\n      \"evidence\": \"Exome sequencing, shRNA knockdown with wild-type vs. mutant rescue, and postmortem Purkinje cell morphology\",\n      \"pmids\": [\"29127138\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Biochemical defect conferred by E1044K not defined\", \"Mechanism linking neurite changes to tremor/epilepsy unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defining a synaptic plasticity mechanism, Ctnnd2 knockout reduced hippocampal Rictor, actin polymerization, and spine density, placing CTNND2 upstream of an mTORC2 axis controlling spatial cognition.\",\n      \"evidence\": \"Ctnnd2 KO mice, Morris water maze, Golgi staining, and Rictor shRNA epistasis\",\n      \"pmids\": [\"34455763\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical link between CTNND2 and Rictor not shown\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying CTNND2's principal synaptic role, it was shown to partner SRGAP2 to slow synaptic maturation and maintain synapses, retain SYNGAP1, and be amplified at human synapses by SRGAP2C.\",\n      \"evidence\": \"Reciprocal co-IP, synaptic fractionation, loss-of-function phenotyping, and SRGAP2C gain-of-function in human neurons\",\n      \"pmids\": [\"39352808\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of SRGAP2\\u2013CTNND2 interaction unresolved\", \"Mechanism by which CTNND2 loss depletes SYNGAP1 not detailed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extending CTNND2 to epithelial biology, TMEM97 was shown to suppress CTNND2 levels, with CTNND2 driving ADAM10 expression and partial EMT in retinal pigment epithelial cells.\",\n      \"evidence\": \"TMEM97 KO and re-expression in ARPE19 cells with integrated proteomics and transcriptomics\",\n      \"pmids\": [\"39995975\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of TMEM97-dependent CTNND2 regulation unknown\", \"Relevance to in vivo RPE pathology untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Two models refined CTNND2's developmental and synaptic roles: loss-of-function disrupted early neurogenesis via dysregulated WNT signaling, and haploinsufficiency reduced synaptic AMPA receptor anchoring with social and fear-learning deficits.\",\n      \"evidence\": \"Patient-derived NSC/CRISPR KO lines with WNT modulation rescue (preprint); heterozygous KO and G34S knock-in mice with synaptic biochemistry and behavior (preprint)\",\n      \"pmids\": [\"41502569\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Both findings from preprints not yet peer-reviewed\", \"Direct mechanism coupling CTNND2 to WNT pathway components not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CTNND2's diverse activities\\u2014synaptic AMPA receptor anchoring, beta-catenin/WNT regulation, and SPHK1-driven motility\\u2014are coordinated within a single molecular framework remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model integrating armadillo-repeat partner binding\", \"Whether nuclear and synaptic pools represent distinct functional states is unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [11, 14]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [11, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 11]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [4, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007409\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 13]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [11, 14]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8, 13]}\n    ],\n    \"complexes\": [\n      \"GSK-3beta/beta-catenin/APC destruction complex\"\n    ],\n    \"partners\": [\n      \"SRGAP2\",\n      \"SPHK1\",\n      \"GSK3B\",\n      \"CTNNB1\",\n      \"APC\",\n      \"DNM2\",\n      \"PSEN1\",\n      \"CDH2\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}