{"gene":"CNTN2","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":1996,"finding":"TAG-1/axonin-1 (CNTN2) is a high-affinity ligand of the chondroitin sulfate proteoglycans neurocan (Kd ~0.3 nM) and phosphacan/PTP-zeta/beta (Kd ~0.04 nM), as well as N-CAM (Kd ~1 nM) and tenascin-C (Kd ~9 nM), demonstrated by direct binding assays. Chondroitinase treatment reduced phosphacan binding ~70% but did not affect neurocan binding, showing differential contributions of chondroitin sulfate chains.","method":"Solid-phase binding assays with purified proteins, chondroitinase and N-deglycosylation treatments, immunocytochemistry","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstituted binding assays with purified proteins, multiple ligands tested with enzymatic perturbations, replicated across multiple binding partners","pmids":["8663515"],"is_preprint":false},{"year":1998,"finding":"TAG-1 (CNTN2) undergoes a cis-interaction with L1-CAM in the plane of the plasma membrane (shown by co-immunoprecipitation from cells co-expressing both molecules). TAG-1 homophilic trans-interaction then cis-activates L1-CAM to recruit the membrane skeleton protein ankyrin to sites of cell contact, providing a mechanism by which the GPI-anchored TAG-1 transduces signals to the cytoplasm via L1-CAM.","method":"Co-immunoprecipitation from Drosophila S2 cells co-expressing L1-CAM and TAG-1; immunolabeling of mixed cell populations; cell aggregation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP, mixed-cell immunolabeling with functional readout (ankyrin recruitment), two orthogonal methods in one study","pmids":["9837910"],"is_preprint":false},{"year":2001,"finding":"Axonin-1/TAG-1 (CNTN2) mediates homophilic cell-cell adhesion through two cooperative binding regions: an N-terminal Ig-domain region and a C-terminal fibronectin type III domain region (Fn3/4). Blocking either region alone abolished cell aggregation entirely, supporting a cis-assisted trans-binding model in which N-terminal regions form a linear zipper-like trans-interaction and C-terminal regions expand the contact into a 2D array via cis-interactions.","method":"Domain-specific monoclonal antibody interference in cell aggregation assay; crystal structure of N-terminal Ig domains (referenced); perturbation of each binding region","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — functional cell aggregation assays with domain-specific antibodies, supported by crystal structure, multiple binding regions tested","pmids":["11733523"],"is_preprint":false},{"year":2008,"finding":"TAG-1 (CNTN2) expressed by retinal ganglion cells (RGCs) and postnatal myelin-forming cells is required for normal caliber of RGC axons and astroglial network organization in the optic nerve. Loss of Tag-1 in null mice causes RGC axon loss, persistent abnormalities of axonal caliber, cytoskeleton defects, and myelination defects, establishing TAG-1 as an essential regulator of RGC axon structure and surrounding glial cells.","method":"Tag-1 knockout mouse analysis; histology, electron microscopy, immunostaining of optic nerve; in situ hybridization for expression timing","journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with multiple defined phenotypic readouts (axon caliber, myelination, glial organization) using orthogonal methods","pmids":["18650339"],"is_preprint":false},{"year":2008,"finding":"Axonin-1/TAG-1 (CNTN2) is required for proper navigation (pathfinding) but not elongation of granule cell parallel fibers in the developing cerebellum. In the absence of axonin-1 (knocked down by ex ovo RNAi in chick), parallel fibers fail to maintain their parallel orientation relative to each other and to the pial surface.","method":"Ex ovo RNAi knockdown in chicken embryo cerebellum; histological analysis of parallel fiber orientation","journal":"Neural development","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean in vivo knockdown with specific phenotypic readout, single lab, single method","pmids":["18346270"],"is_preprint":false},{"year":2013,"finding":"A homozygous frameshift mutation in CNTN2 (c.503_503delG, p.Trp168fs) co-segregates with autosomal recessive cortical myoclonic tremor and epilepsy in a consanguineous family, establishing loss-of-function of CNTN2/contactin-2 as causative. CNTN2 protein, together with CNTNAP2/CASPR2, is required to maintain voltage-gated potassium channels at the juxtaparanodal region of myelinated fibers.","method":"Multipoint linkage analysis, exome sequencing, Sanger sequencing for segregation; functional context from knockout mouse and CNTNAP2 literature","journal":"Brain : a journal of neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — human genetic mutation with segregation, functional inference from knockout mice, single family","pmids":["23518707"],"is_preprint":false},{"year":2016,"finding":"The ectodomains of CNTNAP2 and CNTN2 (contactin 2) bind directly and specifically with low nanomolar affinity, demonstrated biochemically. The molecular architecture of CNTNAP2 (revealed by electron microscopy) is organized into large, medium, and small lobes and is distinct from neurexin-1α, suggesting CNTN2/CNTNAP2 use a unique strategy for integration into the synaptic protein network.","method":"Electron microscopy of CNTNAP2; direct binding assay between CNTNAP2 and CNTN2 ectodomains; epitope labeling with domain fragments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro binding assay with purified ectodomains plus structural EM with domain assignment, two orthogonal methods","pmids":["27621318"],"is_preprint":false},{"year":2017,"finding":"CNTN2/TAG-1 expressed in oligodendrocytes is required for normal oligodendrocyte branching, myelin-gene expression, myelination of fiber tracts, and axonal conduction. CNTN2 absence causes hypomyelination and impaired axonal conduction. During remyelination after cuprizone-induced demyelination, CNTN2 absence does not affect the extent of remyelination but a CNTN2-independent mechanism can recluster voltage-gated potassium channels (VGKCs) and improve fiber conduction.","method":"CNTN2 knockout mice; in vivo and in vitro oligodendrocyte assays; ultrastructural (EM) analysis; electrophysiology; cuprizone demyelination model","journal":"Glia","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic KO with multiple orthogonal methods (EM, electrophysiology, in vitro differentiation assays, disease model), single lab","pmids":["29165835"],"is_preprint":false},{"year":2019,"finding":"Patient-derived anti-CASPR2 autoantibodies impede the CASPR2/TAG-1 (CNTN2) protein-protein interaction in a HEK cell model. The specific domains of CASPR2 and TAG-1 mediating this interaction were identified. Introduction of CASPR2 into HEK cells increases surface Kv1.2 expression, and anti-CASPR2 antibodies further increase Kv1.2 surface expression, establishing that the CASPR2-TAG-1 complex regulates Kv1 channel surface levels.","method":"HEK cell transfection with CASPR2 and CNTN2/TAG-1; anti-CASPR2 patient autoantibody perturbation experiments; domain mapping; surface Kv1.2 quantification; hippocampal neuron cultures","journal":"Journal of autoimmunity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cell-based assays with patient antibodies and domain mapping, two orthogonal cellular systems, single lab","pmids":["31176559"],"is_preprint":false},{"year":2015,"finding":"RACK1 interacts with CNTN2 (contactin-2) as shown by co-immunoprecipitation, and RACK1 upregulates CNTN2 expression. RACK1 promotes glioma cell proliferation and inhibits differentiation via the RTK/Ras/MAPK pathway, and these effects are abolished by CNTN2 siRNA knockdown, placing CNTN2 downstream of RACK1 in this signaling axis.","method":"Co-immunoprecipitation; siRNA knockdown of CNTN2; gain- and loss-of-function experiments; western blot for RTK/Ras/MAPK pathway components","journal":"International journal of molecular medicine","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single Co-IP plus siRNA epistasis, single lab, single study","pmids":["26718491"],"is_preprint":false},{"year":1993,"finding":"The human CNTN2 gene (TAX1/TAX-1 locus) was cloned and mapped to chromosome 1q32 by in situ hybridization. The encoded protein (TAG-1/axonin-1 homologue) contains six IgC2 domains and four fibronectin type III repeats, with a C-terminal hydrophobic sequence consistent with GPI membrane anchoring, and an RGD integrin-recognition motif.","method":"cDNA cloning; sequence analysis; chromosomal in situ hybridization","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cloning and chromosomal mapping with sequence-based domain identification; foundational structural characterization","pmids":["8307567"],"is_preprint":false},{"year":2001,"finding":"In the fish visual pathway, TAG-1 (CNTN2) expression is topographically restricted to nasal retinal ganglion cells and their axons. After optic nerve axotomy, TAG-1 is re-expressed in regenerating RGCs only when axons reach the tectum (target), and re-expression ceases upon interruption of the regenerating projection, establishing that TAG-1 re-expression during regeneration is target contact-dependent.","method":"In situ hybridization; immunohistochemistry with species-specific antibodies; optic nerve lesion/re-lesion experiments in goldfish; developmental zebrafish analysis","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo lesion experiments with temporal controls, two orthogonal detection methods, functional inference from re-lesion experiment","pmids":["11178876"],"is_preprint":false},{"year":2001,"finding":"Thyroid hormone negatively regulates TAG-1 (CNTN2) expression in the developing rat brain: hypothyroidism upregulates TAG-1 RNA and protein in cerebral cortex, hippocampus, olfactory bulb, and cerebellum, and thyroid hormone administration reverses this overexpression.","method":"In situ hybridization; immunohistochemistry; western blotting in hypothyroid vs. thyroid hormone-treated rats","journal":"The European journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — multiple detection methods (ISH, IHC, WB), hormone rescue experiment, single lab","pmids":["11703450"],"is_preprint":false}],"current_model":"CNTN2/TAG-1 is a GPI-anchored neuronal cell adhesion molecule of the immunoglobulin superfamily (6 Ig + 4 FNIII domains, chromosome 1q32) that mediates homophilic cell-cell adhesion through a cis-assisted trans-binding mechanism involving cooperative N-terminal Ig and C-terminal FNIII domains; it binds heterophilic ligands including neurocan, phosphacan/PTP-zeta, N-CAM, tenascin-C, and CNTNAP2/CASPR2 (with which it forms a juxtaparanodal complex required for correct Kv1 potassium channel positioning); it cis-interacts with L1-CAM to recruit ankyrin to cell contacts, providing a cytoplasmic signaling route for this GPI-anchored protein; it is essential for RGC axon structure, parallel fiber pathfinding in the cerebellum, oligodendrocyte branching, myelination, and axonal conduction; and loss-of-function mutations cause epilepsy in humans."},"narrative":{"mechanistic_narrative":"CNTN2 (TAG-1/axonin-1) is a GPI-anchored neuronal cell adhesion molecule of the immunoglobulin superfamily that mediates axon guidance, myelination, and the molecular organization of myelinated fibers [PMID:18650339, PMID:29165835, PMID:8307567]. Cloning established a protein architecture of six IgC2 domains and four fibronectin type III repeats with a C-terminal GPI-anchoring sequence and an RGD motif [PMID:8307567]. It mediates homophilic cell-cell adhesion through two cooperative binding regions — an N-terminal Ig region and a C-terminal Fn3/4 region — consistent with a cis-assisted trans-binding model in which N-terminal regions form a zipper-like trans-interaction and C-terminal regions expand the contact laterally [PMID:11733523]. Heterophilically, it binds with high affinity to the chondroitin sulfate proteoglycans neurocan and phosphacan/PTP-zeta as well as N-CAM and tenascin-C [PMID:8663515], and it cis-associates with L1-CAM so that homophilic trans-binding cis-activates L1-CAM to recruit ankyrin, providing a cytoplasmic signaling route for this GPI-anchored protein [PMID:9837910]. CNTN2 binds the ectodomain of CNTNAP2/CASPR2 with low nanomolar affinity [PMID:27621318], and this CASPR2-CNTN2 complex regulates surface levels of Kv1 voltage-gated potassium channels and their maintenance at the juxtaparanodal region of myelinated axons [PMID:23518707, PMID:31176559]. Genetic loss of CNTN2 in mice disrupts retinal ganglion cell axon caliber, cytoskeleton, and surrounding glial organization in the optic nerve [PMID:18650339], impairs cerebellar parallel fiber pathfinding [PMID:18346270], and causes oligodendrocyte branching defects, hypomyelination, and impaired axonal conduction [PMID:29165835]. A homozygous frameshift mutation in CNTN2 causes autosomal recessive cortical myoclonic tremor and epilepsy in humans [PMID:23518707].","teleology":[{"year":1993,"claim":"Establishing the gene's identity and protein architecture defined CNTN2 as a GPI-anchored Ig-superfamily adhesion molecule, framing all subsequent functional work.","evidence":"cDNA cloning, sequence analysis, and chromosomal in situ hybridization of the human TAX1 locus","pmids":["8307567"],"confidence":"Medium","gaps":["Domain boundaries inferred from sequence, not structure","No functional assay in this study"]},{"year":1996,"claim":"Identifying high-affinity heterophilic ligands moved CNTN2 from a bare adhesion molecule to a node interacting with the extracellular matrix and other CAMs.","evidence":"Solid-phase binding assays with purified proteins, with chondroitinase and deglycosylation perturbations","pmids":["8663515"],"confidence":"High","gaps":["In vitro binding does not establish in vivo functional consequence of each interaction","Binding-site domains on CNTN2 not mapped"]},{"year":1998,"claim":"Demonstrating cis-association with L1-CAM and ankyrin recruitment solved how a GPI-anchored protein with no cytoplasmic tail transduces signals across the membrane.","evidence":"Reciprocal co-IP from S2 cells, mixed-cell immunolabeling, and aggregation assays","pmids":["9837910"],"confidence":"High","gaps":["Heterologous cell system, not neurons","Downstream signaling consequences of ankyrin recruitment not traced"]},{"year":2001,"claim":"Mapping homophilic adhesion to two cooperative N- and C-terminal regions defined the cis-assisted trans-binding mechanism of adhesion.","evidence":"Domain-specific antibody interference in cell aggregation assays, supported by crystal structure of N-terminal Ig domains","pmids":["11733523"],"confidence":"High","gaps":["Full-length structure of trans/cis assembly not solved","Stoichiometry of the 2D array inferred"]},{"year":2001,"claim":"Topographically restricted, target-contact-dependent re-expression during optic nerve regeneration linked CNTN2 expression to functional axon-target connectivity.","evidence":"In situ hybridization, immunohistochemistry, and optic nerve lesion/re-lesion experiments in goldfish","pmids":["11178876"],"confidence":"Medium","gaps":["Signal driving target-dependent re-expression unidentified","Single species"]},{"year":2001,"claim":"Identifying thyroid hormone as a negative regulator placed CNTN2 expression under endocrine control during brain development.","evidence":"In situ hybridization, IHC, and western blotting in hypothyroid versus hormone-treated rats","pmids":["11703450"],"confidence":"Medium","gaps":["Transcriptional mechanism of regulation not defined","Functional consequence of overexpression not measured"]},{"year":2008,"claim":"Knockout phenotypes established CNTN2 as essential for RGC axon structure and for cerebellar parallel fiber pathfinding, demonstrating in vivo developmental roles.","evidence":"Tag-1 knockout mouse optic nerve histology/EM, and ex ovo RNAi knockdown in chick cerebellum","pmids":["18650339","18346270"],"confidence":"Medium","gaps":["Molecular partners mediating each phenotype not pinned down","Parallel fiber result from knockdown in a single species"]},{"year":2013,"claim":"A segregating frameshift mutation established CNTN2 loss-of-function as causative for human autosomal recessive cortical myoclonic tremor and epilepsy.","evidence":"Linkage analysis, exome and Sanger sequencing for segregation in a consanguineous family, with functional context from CNTNAP2 literature","pmids":["23518707"],"confidence":"Medium","gaps":["Single family","Disease mechanism inferred from juxtaparanodal channel maintenance, not directly demonstrated in patients"]},{"year":2015,"claim":"Linking CNTN2 to RACK1 and the RTK/Ras/MAPK axis implicated it in glioma proliferation downstream of an intracellular scaffold.","evidence":"Co-IP, siRNA knockdown, and gain/loss-of-function experiments in glioma cells","pmids":["26718491"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation in this context","How a GPI-anchored protein connects to RACK1 mechanistically unclear"]},{"year":2016,"claim":"Direct, low-nanomolar binding between CNTN2 and CNTNAP2 ectodomains, with EM architecture, established the biochemical basis of the juxtaparanodal complex.","evidence":"Direct binding assays with purified ectodomains and electron microscopy with domain assignment","pmids":["27621318"],"confidence":"High","gaps":["High-resolution complex structure not determined","Cis versus trans configuration in the axon membrane not resolved"]},{"year":2017,"claim":"Oligodendrocyte-expressed CNTN2 was shown necessary for branching, myelin-gene expression, myelination, and conduction, expanding its role beyond axons to myelinating glia.","evidence":"CNTN2 knockout mice, in vitro oligodendrocyte assays, EM, electrophysiology, and cuprizone demyelination model","pmids":["29165835"],"confidence":"High","gaps":["The CNTN2-independent mechanism that reclusters VGKCs during remyelination not identified","Molecular partners in oligodendrocytes not defined"]},{"year":2019,"claim":"Showing that anti-CASPR2 autoantibodies disrupt the CASPR2/CNTN2 interaction and alter surface Kv1.2 connected the complex to autoimmune channel dysregulation.","evidence":"HEK cell transfection, patient autoantibody perturbation, domain mapping, and surface Kv1.2 quantification with hippocampal cultures","pmids":["31176559"],"confidence":"Medium","gaps":["Heterologous and cultured systems, not in vivo","Single lab"]},{"year":null,"claim":"The cytoplasmic signaling output of CNTN2 in neurons and the molecular identity of the CNTN2-independent VGKC-reclustering mechanism during remyelination remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["In-neuron downstream signaling beyond ankyrin recruitment uncharacterized","Compensatory channel-clustering pathway unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[1,2]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1,6,8]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[3,10]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,8,10]}],"pathway":[{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[3,4,7]},{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[0,1,6]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[5,7,8]}],"complexes":["CNTN2-CNTNAP2/CASPR2 juxtaparanodal complex"],"partners":["CNTNAP2","L1CAM","NCAN","PTPRZ1","NCAM1","TNC","RACK1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q02246","full_name":"Contactin-2","aliases":["Axonal glycoprotein TAG-1","Axonin-1","Transient axonal glycoprotein 1","TAX-1"],"length_aa":1040,"mass_kda":113.4,"function":"In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. May be involved in cell adhesion","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q02246/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CNTN2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CNTN2","total_profiled":1310},"omim":[{"mim_id":"617290","title":"EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT; EPEO1","url":"https://www.omim.org/entry/617290"},{"mim_id":"615400","title":"EPILEPSY, EARLY-ONSET, 5, WITH OR WITHOUT DEVELOPMENTAL DELAY; EPEO5","url":"https://www.omim.org/entry/615400"},{"mim_id":"607220","title":"CONTACTIN 6; CNTN6","url":"https://www.omim.org/entry/607220"},{"mim_id":"607219","title":"CONTACTIN 5; CNTN5","url":"https://www.omim.org/entry/607219"},{"mim_id":"190197","title":"CONTACTIN 2; CNTN2","url":"https://www.omim.org/entry/190197"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":157.3}],"url":"https://www.proteinatlas.org/search/CNTN2"},"hgnc":{"alias_symbol":["TAG-1","TAX1"],"prev_symbol":["TAX","AXT"]},"alphafold":{"accession":"Q02246","domains":[{"cath_id":"2.60.40.10","chopping":"34-129","consensus_level":"high","plddt":91.4779,"start":34,"end":129},{"cath_id":"2.60.40.10","chopping":"143-235","consensus_level":"medium","plddt":88.9814,"start":143,"end":235},{"cath_id":"2.60.40.10","chopping":"236-325","consensus_level":"medium","plddt":89.4658,"start":236,"end":325},{"cath_id":"2.60.40.10","chopping":"332-412","consensus_level":"high","plddt":92.191,"start":332,"end":412},{"cath_id":"2.60.40.10","chopping":"417-505","consensus_level":"high","plddt":91.4146,"start":417,"end":505},{"cath_id":"2.60.40.10","chopping":"509-604","consensus_level":"high","plddt":90.7816,"start":509,"end":604},{"cath_id":"2.60.40.10","chopping":"611-703","consensus_level":"high","plddt":92.3028,"start":611,"end":703},{"cath_id":"2.60.40.10","chopping":"714-806","consensus_level":"medium","plddt":89.3881,"start":714,"end":806},{"cath_id":"2.60.40.10","chopping":"816-905","consensus_level":"medium","plddt":88.3446,"start":816,"end":905},{"cath_id":"2.60.40.10","chopping":"916-1000","consensus_level":"medium","plddt":82.5815,"start":916,"end":1000}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q02246","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q02246-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q02246-F1-predicted_aligned_error_v6.png","plddt_mean":85.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CNTN2","jax_strain_url":"https://www.jax.org/strain/search?query=CNTN2"},"sequence":{"accession":"Q02246","fasta_url":"https://rest.uniprot.org/uniprotkb/Q02246.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q02246/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q02246"}},"corpus_meta":[{"pmid":"2847164","id":"PMC_2847164","title":"c-fos 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Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31835460","citation_count":23,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46654,"output_tokens":3952,"usd":0.099621,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11369,"output_tokens":3802,"usd":0.075948,"stage2_stop_reason":"end_turn"},"total_usd":0.175569,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the corpus, I need to distinguish between two completely different genes sharing symbols in this corpus:\n\n1. **CNTN2/TAG-1/TAX1** (the canonical gene) — a neuronal cell adhesion molecule, immunoglobulin superfamily, GPI-anchored\n2. **HTLV-1 Tax / Tax1** — a viral oncoprotein from human T-cell leukemia virus type I\n\nThe HGNC aliases listed (TAG-1, TAX1, TAX, AXT) refer to the neuronal adhesion molecule CNTN2. The vast majority of papers in this corpus describe the HTLV-1 viral Tax protein — a completely different entity that happens to share the \"Tax1\" alias through a symbol collision. I must exclude those.\n\nPapers relevant to CNTN2 (the neuronal cell adhesion molecule): [7], [30], [38], [46], [48], [54], [57], [70], [72], [75], [76], [80], [86], [87], [92]\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"TAG-1/axonin-1 (CNTN2) is a high-affinity ligand of the chondroitin sulfate proteoglycans neurocan (Kd ~0.3 nM) and phosphacan/PTP-zeta/beta (Kd ~0.04 nM), as well as N-CAM (Kd ~1 nM) and tenascin-C (Kd ~9 nM), demonstrated by direct binding assays. Chondroitinase treatment reduced phosphacan binding ~70% but did not affect neurocan binding, showing differential contributions of chondroitin sulfate chains.\",\n      \"method\": \"Solid-phase binding assays with purified proteins, chondroitinase and N-deglycosylation treatments, immunocytochemistry\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstituted binding assays with purified proteins, multiple ligands tested with enzymatic perturbations, replicated across multiple binding partners\",\n      \"pmids\": [\"8663515\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"TAG-1 (CNTN2) undergoes a cis-interaction with L1-CAM in the plane of the plasma membrane (shown by co-immunoprecipitation from cells co-expressing both molecules). TAG-1 homophilic trans-interaction then cis-activates L1-CAM to recruit the membrane skeleton protein ankyrin to sites of cell contact, providing a mechanism by which the GPI-anchored TAG-1 transduces signals to the cytoplasm via L1-CAM.\",\n      \"method\": \"Co-immunoprecipitation from Drosophila S2 cells co-expressing L1-CAM and TAG-1; immunolabeling of mixed cell populations; cell aggregation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP, mixed-cell immunolabeling with functional readout (ankyrin recruitment), two orthogonal methods in one study\",\n      \"pmids\": [\"9837910\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Axonin-1/TAG-1 (CNTN2) mediates homophilic cell-cell adhesion through two cooperative binding regions: an N-terminal Ig-domain region and a C-terminal fibronectin type III domain region (Fn3/4). Blocking either region alone abolished cell aggregation entirely, supporting a cis-assisted trans-binding model in which N-terminal regions form a linear zipper-like trans-interaction and C-terminal regions expand the contact into a 2D array via cis-interactions.\",\n      \"method\": \"Domain-specific monoclonal antibody interference in cell aggregation assay; crystal structure of N-terminal Ig domains (referenced); perturbation of each binding region\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — functional cell aggregation assays with domain-specific antibodies, supported by crystal structure, multiple binding regions tested\",\n      \"pmids\": [\"11733523\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"TAG-1 (CNTN2) expressed by retinal ganglion cells (RGCs) and postnatal myelin-forming cells is required for normal caliber of RGC axons and astroglial network organization in the optic nerve. Loss of Tag-1 in null mice causes RGC axon loss, persistent abnormalities of axonal caliber, cytoskeleton defects, and myelination defects, establishing TAG-1 as an essential regulator of RGC axon structure and surrounding glial cells.\",\n      \"method\": \"Tag-1 knockout mouse analysis; histology, electron microscopy, immunostaining of optic nerve; in situ hybridization for expression timing\",\n      \"journal\": \"The Journal of neuroscience : the official journal of the Society for Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with multiple defined phenotypic readouts (axon caliber, myelination, glial organization) using orthogonal methods\",\n      \"pmids\": [\"18650339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Axonin-1/TAG-1 (CNTN2) is required for proper navigation (pathfinding) but not elongation of granule cell parallel fibers in the developing cerebellum. In the absence of axonin-1 (knocked down by ex ovo RNAi in chick), parallel fibers fail to maintain their parallel orientation relative to each other and to the pial surface.\",\n      \"method\": \"Ex ovo RNAi knockdown in chicken embryo cerebellum; histological analysis of parallel fiber orientation\",\n      \"journal\": \"Neural development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean in vivo knockdown with specific phenotypic readout, single lab, single method\",\n      \"pmids\": [\"18346270\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"A homozygous frameshift mutation in CNTN2 (c.503_503delG, p.Trp168fs) co-segregates with autosomal recessive cortical myoclonic tremor and epilepsy in a consanguineous family, establishing loss-of-function of CNTN2/contactin-2 as causative. CNTN2 protein, together with CNTNAP2/CASPR2, is required to maintain voltage-gated potassium channels at the juxtaparanodal region of myelinated fibers.\",\n      \"method\": \"Multipoint linkage analysis, exome sequencing, Sanger sequencing for segregation; functional context from knockout mouse and CNTNAP2 literature\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — human genetic mutation with segregation, functional inference from knockout mice, single family\",\n      \"pmids\": [\"23518707\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The ectodomains of CNTNAP2 and CNTN2 (contactin 2) bind directly and specifically with low nanomolar affinity, demonstrated biochemically. The molecular architecture of CNTNAP2 (revealed by electron microscopy) is organized into large, medium, and small lobes and is distinct from neurexin-1α, suggesting CNTN2/CNTNAP2 use a unique strategy for integration into the synaptic protein network.\",\n      \"method\": \"Electron microscopy of CNTNAP2; direct binding assay between CNTNAP2 and CNTN2 ectodomains; epitope labeling with domain fragments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro binding assay with purified ectodomains plus structural EM with domain assignment, two orthogonal methods\",\n      \"pmids\": [\"27621318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CNTN2/TAG-1 expressed in oligodendrocytes is required for normal oligodendrocyte branching, myelin-gene expression, myelination of fiber tracts, and axonal conduction. CNTN2 absence causes hypomyelination and impaired axonal conduction. During remyelination after cuprizone-induced demyelination, CNTN2 absence does not affect the extent of remyelination but a CNTN2-independent mechanism can recluster voltage-gated potassium channels (VGKCs) and improve fiber conduction.\",\n      \"method\": \"CNTN2 knockout mice; in vivo and in vitro oligodendrocyte assays; ultrastructural (EM) analysis; electrophysiology; cuprizone demyelination model\",\n      \"journal\": \"Glia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with multiple orthogonal methods (EM, electrophysiology, in vitro differentiation assays, disease model), single lab\",\n      \"pmids\": [\"29165835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Patient-derived anti-CASPR2 autoantibodies impede the CASPR2/TAG-1 (CNTN2) protein-protein interaction in a HEK cell model. The specific domains of CASPR2 and TAG-1 mediating this interaction were identified. Introduction of CASPR2 into HEK cells increases surface Kv1.2 expression, and anti-CASPR2 antibodies further increase Kv1.2 surface expression, establishing that the CASPR2-TAG-1 complex regulates Kv1 channel surface levels.\",\n      \"method\": \"HEK cell transfection with CASPR2 and CNTN2/TAG-1; anti-CASPR2 patient autoantibody perturbation experiments; domain mapping; surface Kv1.2 quantification; hippocampal neuron cultures\",\n      \"journal\": \"Journal of autoimmunity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cell-based assays with patient antibodies and domain mapping, two orthogonal cellular systems, single lab\",\n      \"pmids\": [\"31176559\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"RACK1 interacts with CNTN2 (contactin-2) as shown by co-immunoprecipitation, and RACK1 upregulates CNTN2 expression. RACK1 promotes glioma cell proliferation and inhibits differentiation via the RTK/Ras/MAPK pathway, and these effects are abolished by CNTN2 siRNA knockdown, placing CNTN2 downstream of RACK1 in this signaling axis.\",\n      \"method\": \"Co-immunoprecipitation; siRNA knockdown of CNTN2; gain- and loss-of-function experiments; western blot for RTK/Ras/MAPK pathway components\",\n      \"journal\": \"International journal of molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP plus siRNA epistasis, single lab, single study\",\n      \"pmids\": [\"26718491\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1993,\n      \"finding\": \"The human CNTN2 gene (TAX1/TAX-1 locus) was cloned and mapped to chromosome 1q32 by in situ hybridization. The encoded protein (TAG-1/axonin-1 homologue) contains six IgC2 domains and four fibronectin type III repeats, with a C-terminal hydrophobic sequence consistent with GPI membrane anchoring, and an RGD integrin-recognition motif.\",\n      \"method\": \"cDNA cloning; sequence analysis; chromosomal in situ hybridization\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cloning and chromosomal mapping with sequence-based domain identification; foundational structural characterization\",\n      \"pmids\": [\"8307567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"In the fish visual pathway, TAG-1 (CNTN2) expression is topographically restricted to nasal retinal ganglion cells and their axons. After optic nerve axotomy, TAG-1 is re-expressed in regenerating RGCs only when axons reach the tectum (target), and re-expression ceases upon interruption of the regenerating projection, establishing that TAG-1 re-expression during regeneration is target contact-dependent.\",\n      \"method\": \"In situ hybridization; immunohistochemistry with species-specific antibodies; optic nerve lesion/re-lesion experiments in goldfish; developmental zebrafish analysis\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo lesion experiments with temporal controls, two orthogonal detection methods, functional inference from re-lesion experiment\",\n      \"pmids\": [\"11178876\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Thyroid hormone negatively regulates TAG-1 (CNTN2) expression in the developing rat brain: hypothyroidism upregulates TAG-1 RNA and protein in cerebral cortex, hippocampus, olfactory bulb, and cerebellum, and thyroid hormone administration reverses this overexpression.\",\n      \"method\": \"In situ hybridization; immunohistochemistry; western blotting in hypothyroid vs. thyroid hormone-treated rats\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multiple detection methods (ISH, IHC, WB), hormone rescue experiment, single lab\",\n      \"pmids\": [\"11703450\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CNTN2/TAG-1 is a GPI-anchored neuronal cell adhesion molecule of the immunoglobulin superfamily (6 Ig + 4 FNIII domains, chromosome 1q32) that mediates homophilic cell-cell adhesion through a cis-assisted trans-binding mechanism involving cooperative N-terminal Ig and C-terminal FNIII domains; it binds heterophilic ligands including neurocan, phosphacan/PTP-zeta, N-CAM, tenascin-C, and CNTNAP2/CASPR2 (with which it forms a juxtaparanodal complex required for correct Kv1 potassium channel positioning); it cis-interacts with L1-CAM to recruit ankyrin to cell contacts, providing a cytoplasmic signaling route for this GPI-anchored protein; it is essential for RGC axon structure, parallel fiber pathfinding in the cerebellum, oligodendrocyte branching, myelination, and axonal conduction; and loss-of-function mutations cause epilepsy in humans.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CNTN2 (TAG-1/axonin-1) is a GPI-anchored neuronal cell adhesion molecule of the immunoglobulin superfamily that mediates axon guidance, myelination, and the molecular organization of myelinated fibers [#3, #7, #10]. Cloning established a protein architecture of six IgC2 domains and four fibronectin type III repeats with a C-terminal GPI-anchoring sequence and an RGD motif [#10]. It mediates homophilic cell-cell adhesion through two cooperative binding regions — an N-terminal Ig region and a C-terminal Fn3/4 region — consistent with a cis-assisted trans-binding model in which N-terminal regions form a zipper-like trans-interaction and C-terminal regions expand the contact laterally [#2]. Heterophilically, it binds with high affinity to the chondroitin sulfate proteoglycans neurocan and phosphacan/PTP-zeta as well as N-CAM and tenascin-C [#0], and it cis-associates with L1-CAM so that homophilic trans-binding cis-activates L1-CAM to recruit ankyrin, providing a cytoplasmic signaling route for this GPI-anchored protein [#1]. CNTN2 binds the ectodomain of CNTNAP2/CASPR2 with low nanomolar affinity [#6], and this CASPR2-CNTN2 complex regulates surface levels of Kv1 voltage-gated potassium channels and their maintenance at the juxtaparanodal region of myelinated axons [#5, #8]. Genetic loss of CNTN2 in mice disrupts retinal ganglion cell axon caliber, cytoskeleton, and surrounding glial organization in the optic nerve [#3], impairs cerebellar parallel fiber pathfinding [#4], and causes oligodendrocyte branching defects, hypomyelination, and impaired axonal conduction [#7]. A homozygous frameshift mutation in CNTN2 causes autosomal recessive cortical myoclonic tremor and epilepsy in humans [#5].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Establishing the gene's identity and protein architecture defined CNTN2 as a GPI-anchored Ig-superfamily adhesion molecule, framing all subsequent functional work.\",\n      \"evidence\": \"cDNA cloning, sequence analysis, and chromosomal in situ hybridization of the human TAX1 locus\",\n      \"pmids\": [\"8307567\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Domain boundaries inferred from sequence, not structure\", \"No functional assay in this study\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Identifying high-affinity heterophilic ligands moved CNTN2 from a bare adhesion molecule to a node interacting with the extracellular matrix and other CAMs.\",\n      \"evidence\": \"Solid-phase binding assays with purified proteins, with chondroitinase and deglycosylation perturbations\",\n      \"pmids\": [\"8663515\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vitro binding does not establish in vivo functional consequence of each interaction\", \"Binding-site domains on CNTN2 not mapped\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Demonstrating cis-association with L1-CAM and ankyrin recruitment solved how a GPI-anchored protein with no cytoplasmic tail transduces signals across the membrane.\",\n      \"evidence\": \"Reciprocal co-IP from S2 cells, mixed-cell immunolabeling, and aggregation assays\",\n      \"pmids\": [\"9837910\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Heterologous cell system, not neurons\", \"Downstream signaling consequences of ankyrin recruitment not traced\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapping homophilic adhesion to two cooperative N- and C-terminal regions defined the cis-assisted trans-binding mechanism of adhesion.\",\n      \"evidence\": \"Domain-specific antibody interference in cell aggregation assays, supported by crystal structure of N-terminal Ig domains\",\n      \"pmids\": [\"11733523\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length structure of trans/cis assembly not solved\", \"Stoichiometry of the 2D array inferred\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Topographically restricted, target-contact-dependent re-expression during optic nerve regeneration linked CNTN2 expression to functional axon-target connectivity.\",\n      \"evidence\": \"In situ hybridization, immunohistochemistry, and optic nerve lesion/re-lesion experiments in goldfish\",\n      \"pmids\": [\"11178876\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signal driving target-dependent re-expression unidentified\", \"Single species\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identifying thyroid hormone as a negative regulator placed CNTN2 expression under endocrine control during brain development.\",\n      \"evidence\": \"In situ hybridization, IHC, and western blotting in hypothyroid versus hormone-treated rats\",\n      \"pmids\": [\"11703450\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional mechanism of regulation not defined\", \"Functional consequence of overexpression not measured\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Knockout phenotypes established CNTN2 as essential for RGC axon structure and for cerebellar parallel fiber pathfinding, demonstrating in vivo developmental roles.\",\n      \"evidence\": \"Tag-1 knockout mouse optic nerve histology/EM, and ex ovo RNAi knockdown in chick cerebellum\",\n      \"pmids\": [\"18650339\", \"18346270\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular partners mediating each phenotype not pinned down\", \"Parallel fiber result from knockdown in a single species\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"A segregating frameshift mutation established CNTN2 loss-of-function as causative for human autosomal recessive cortical myoclonic tremor and epilepsy.\",\n      \"evidence\": \"Linkage analysis, exome and Sanger sequencing for segregation in a consanguineous family, with functional context from CNTNAP2 literature\",\n      \"pmids\": [\"23518707\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single family\", \"Disease mechanism inferred from juxtaparanodal channel maintenance, not directly demonstrated in patients\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Linking CNTN2 to RACK1 and the RTK/Ras/MAPK axis implicated it in glioma proliferation downstream of an intracellular scaffold.\",\n      \"evidence\": \"Co-IP, siRNA knockdown, and gain/loss-of-function experiments in glioma cells\",\n      \"pmids\": [\"26718491\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single Co-IP without reciprocal validation in this context\", \"How a GPI-anchored protein connects to RACK1 mechanistically unclear\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Direct, low-nanomolar binding between CNTN2 and CNTNAP2 ectodomains, with EM architecture, established the biochemical basis of the juxtaparanodal complex.\",\n      \"evidence\": \"Direct binding assays with purified ectodomains and electron microscopy with domain assignment\",\n      \"pmids\": [\"27621318\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"High-resolution complex structure not determined\", \"Cis versus trans configuration in the axon membrane not resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Oligodendrocyte-expressed CNTN2 was shown necessary for branching, myelin-gene expression, myelination, and conduction, expanding its role beyond axons to myelinating glia.\",\n      \"evidence\": \"CNTN2 knockout mice, in vitro oligodendrocyte assays, EM, electrophysiology, and cuprizone demyelination model\",\n      \"pmids\": [\"29165835\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The CNTN2-independent mechanism that reclusters VGKCs during remyelination not identified\", \"Molecular partners in oligodendrocytes not defined\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showing that anti-CASPR2 autoantibodies disrupt the CASPR2/CNTN2 interaction and alter surface Kv1.2 connected the complex to autoimmune channel dysregulation.\",\n      \"evidence\": \"HEK cell transfection, patient autoantibody perturbation, domain mapping, and surface Kv1.2 quantification with hippocampal cultures\",\n      \"pmids\": [\"31176559\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Heterologous and cultured systems, not in vivo\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cytoplasmic signaling output of CNTN2 in neurons and the molecular identity of the CNTN2-independent VGKC-reclustering mechanism during remyelination remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In-neuron downstream signaling beyond ankyrin recruitment uncharacterized\", \"Compensatory channel-clustering pathway unidentified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1, 6, 8]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [3, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 8, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [3, 4, 7]},\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [0, 1, 6]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [5, 7, 8]}\n    ],\n    \"complexes\": [\n      \"CNTN2-CNTNAP2/CASPR2 juxtaparanodal complex\"\n    ],\n    \"partners\": [\n      \"CNTNAP2\",\n      \"L1CAM\",\n      \"NCAN\",\n      \"PTPRZ1\",\n      \"NCAM1\",\n      \"TNC\",\n      \"RACK1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}