{"gene":"ELFN1","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2012,"finding":"ELFN1 is selectively expressed by hippocampal O-LM interneurons and, when expressed postsynaptically, regulates presynaptic release probability to direct the formation of highly facilitating (low release probability) pyramidal-O-LM synapses, demonstrating a retrograde transsynaptic signaling role.","method":"Selective expression analysis combined with loss-of-function in identified interneuron subtypes with electrophysiological readout of release probability","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean loss-of-function with defined synaptic phenotype, replicated across subsequent independent studies","pmids":["23042292"],"is_preprint":false},{"year":2013,"finding":"Elfn1 is expressed in distinct subsets of hippocampal and cortical interneurons and also in axons of excitatory habenular neurons and long-range GABAergic globus pallidus neurons; Elfn1 mutant mice exhibit seizures, hyperactivity, and motor abnormalities reversible by amphetamine, establishing an in vivo functional requirement.","method":"β-galactosidase reporter knock-in expression analysis; behavioral phenotyping of knockout mice","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo KO with defined behavioral/neurological phenotype and detailed expression mapping; single lab","pmids":["24312227"],"is_preprint":false},{"year":2014,"finding":"ELFN1 physically interacts in trans with presynaptic mGluR7, recruits mGluR7 to synaptic sites on somatostatin interneurons in the hippocampal CA1 stratum oriens and dentate gyrus, and is required for presynaptic plasticity at these synapses; loss of Elfn1 causes deficits in mGluR7 recruitment and results in hyperactivity and sensory-triggered epileptic seizures in mice. Damaging missense mutations of human ELFN1 cluster in the C-terminal region required for mGluR7 recruitment.","method":"Elfn1 knockout mice, immunolocalization of mGluR7 at synapses, electrophysiological assessment of presynaptic plasticity, human mutation analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal localization data, KO with defined synaptic and in vivo phenotype, replicated by independent labs","pmids":["25047565"],"is_preprint":false},{"year":2018,"finding":"ELFN1 selectively binds all group III mGluRs (mGluR4, mGluR6, mGluR7, mGluR8) but not group I or II mGluRs; binding determinants were mapped to two distinct sites on the ELFN1 ectodomain by site-directed mutagenesis. In a transcellular signaling reconstitution assay in HEK293 cells, ELFN1 acts as a transsynaptic allosteric modulator that suppresses cAMP accumulation and alters both agonist-induced and constitutive group III mGluR activity by altering G protein activation kinetics, as measured by BRET.","method":"Site-directed mutagenesis; transcellular signaling reconstitution assay in HEK293 cells; BRET-based real-time kinetic G protein activation assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution in heterologous cells, mutagenesis mapping of binding sites, orthogonal BRET assay confirming G protein effect","pmids":["29686062"],"is_preprint":false},{"year":2019,"finding":"Elfn1 produces glutamate-independent (constitutive) activation of presynaptic mGluR7 through clustering at cortical pyramidal→somatostatin interneuron synapses, establishing a tonic low release probability. Facilitation at layer 2/3 synapses also depends on presynaptic GluK2-KARs, which can be engaged at layer 5 synapses via calmodulin activation, revealing layer-specific synaptic properties.","method":"Electrophysiology of cortical SOM interneuron synapses in mouse brain slices; pharmacological dissection; loss-of-function for Elfn1 and mGluR7","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — defined electrophysiological mechanism with pharmacological and genetic dissection, builds on replicated prior findings","pmids":["30940718"],"is_preprint":false},{"year":2020,"finding":"N-glycosylation of mGluR7 at four asparagine residues is essential for its forward trafficking and surface expression; deglycosylated mGluR7 is retained in the ER and degraded via the autophagolysosomal pathway. N-glycosylation of mGluR7 promotes its interaction with ELFN1, enabling proper localization and stable surface expression of mGluR7 at the presynaptic active zone.","method":"Mutagenesis of N-glycosylation sites; subcellular fractionation; co-immunoprecipitation of mGluR7 and ELFN1; pharmacological inhibition of glycosylation","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis and co-IP in heterologous cells and neurons; single lab, multiple orthogonal approaches","pmids":["32931036"],"is_preprint":false},{"year":2024,"finding":"The intracellular domain of ELFN1 (a ~30 amino acid juxtamembranous region) controls membrane trafficking and postsynaptic localization of ELFN1. ELFN1 exists as an obligate homodimer prior to membrane trafficking, with homodimerization mediated by the extracellular leucine-rich repeat (LRR) domain rather than the intracellular region. A single membrane-targeting motif in one protomer is sufficient for trafficking of the homodimer. ELFN2 exhibits similar properties and heterodimerizes with ELFN1.","method":"Domain deletion mutagenesis; biochemical fractionation; dimerization assays; synaptic localization imaging","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis with multiple functional readouts (trafficking, localization, dimerization), single lab","pmids":["39675706"],"is_preprint":false},{"year":2024,"finding":"CSNB-associated missense mutations in the extracellular ligand-binding domain of mGluR6 cause a trafficking defect leading to lack of complex N-glycosylation (suggesting Golgi bypass), failure to bind ELFN1, and mislocalization in bipolar cells, establishing that Golgi-acquired N-glycosylation of mGluR6 is required for its interaction with ELFN1 and correct synaptic targeting.","method":"Biochemical glycosylation analysis of mGluR6 mutants; co-immunoprecipitation binding assay with ELFN1; immunolocalization in bipolar cells","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple CSNB mutants tested with co-IP and localization; single lab, two orthogonal methods","pmids":["39681475"],"is_preprint":false},{"year":2025,"finding":"The LRR and LRR C-terminal cap (LRRCT) regions of the ELFN1 extracellular domain are necessary and sufficient for binding to all group III mGluRs including mGluR6; deletion of the LRRCT domain abolishes trafficking of ELFN1 to rod photoreceptor spherules. In mGluR6-null mice, presynaptic ELFN1 localization in rod spherules is disrupted and rescued by re-expressing mGluR6-EGFP in ON-bipolar cells, demonstrating bidirectional transsynaptic mutual stabilization.","method":"In vitro binding assays with ELFN1 deletion constructs; immunolocalization in mGluR6 KO mice; mGluR6-EGFP rescue in ON-bipolar cells","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion mapping plus in vivo rescue experiment; single lab, orthogonal methods","pmids":["40930976"],"is_preprint":false},{"year":2024,"finding":"ELFN1 is expressed in skin fibroblasts and its loss (due to signal-peptide frameshift mutation) dramatically alters fibroblast morphology, growth, proliferation, and motility in an in vitro ECM model, providing experimental evidence that ELFN1 participates in cell–ECM attachment outside the nervous system.","method":"Primary skin fibroblast isolation from ELFN1-mutated patients; in vitro ECM and decellularized ECM models; comparative morphological and motility analysis","journal":"Life sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single patient-derived cell model, no molecular mechanism identified beyond loss of ELFN1 expression","pmids":["38986898"],"is_preprint":false},{"year":2025,"finding":"Biallelic frameshift and in-frame deletion variants in ELFN1 disrupt ELFN1 protein trafficking to the cell surface (loss of function), causing a neurodevelopmental disorder with epilepsy in humans; Elfn1 loss in mice and zebrafish recapitulates motor abnormalities and seizures.","method":"Whole-exome sequencing of affected individuals; cell-surface trafficking assay for ELFN1 variants; behavioral/seizure phenotyping in Elfn1 KO mice and zebrafish","journal":"Genetics in medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional trafficking assay plus two orthologous animal models, multiple unrelated families; single study","pmids":["40576023"],"is_preprint":false},{"year":2025,"finding":"Positive allosteric modulators (PAMs) of mGluR7 show decreased maximal potentiation in the presence of ELFN1 but retain the ability to potentiate receptor signaling; negative allosteric modulators (NAMs) show similar efficacy with or without ELFN1. A tool PAM retains activity at pyramidal cell–somatostatin interneuron synapses where endogenous ELFN1 is expressed.","method":"Transcellular mGluR7 signaling assay in HEK293 cells ± ELFN1; electrophysiology at pyr→SOM synapses in brain slices","journal":"ACS chemical neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reconstituted pharmacology assay plus ex vivo slice electrophysiology; single lab, two orthogonal methods","pmids":["40689847"],"is_preprint":false}],"current_model":"ELFN1 is a postsynaptic (and presynaptic in rods) transmembrane leucine-rich repeat/fibronectin III adhesion molecule that selectively recruits all group III mGluRs (mGluR4/6/7/8) via its extracellular LRR–LRRCT domain in trans, acts as a transsynaptic allosteric modulator suppressing G protein–cAMP signaling and driving constitutive, glutamate-independent mGluR7 activation that sets a low initial release probability at pyramidal→somatostatin interneuron synapses; its trafficking to the postsynaptic membrane requires a ~30 aa juxtamembranous intracellular motif and occurs as an obligate homodimer (dimerization via the LRR ectodomain), while N-glycosylation of its partner mGluR7/mGluR6 is required for stable ELFN1 binding and synaptic localization; loss of ELFN1 function in mice and humans causes impaired interneuron recruitment, epileptic seizures, hyperactivity, and a neurodevelopmental disorder."},"narrative":{"mechanistic_narrative":"ELFN1 is a postsynaptic transmembrane leucine-rich repeat adhesion molecule expressed by defined subsets of hippocampal and cortical interneurons that organizes target-specific synaptic properties through retrograde transsynaptic signaling [PMID:23042292, PMID:24312227]. It physically engages presynaptic group III metabotropic glutamate receptors in trans — binding mGluR4, mGluR6, mGluR7, and mGluR8 but not group I or II mGluRs — via its extracellular LRR/LRRCT module, which is necessary and sufficient for receptor binding and for ELFN1's own synaptic trafficking [PMID:29686062, PMID:40930976]. At pyramidal→somatostatin interneuron synapses ELFN1 recruits and clusters mGluR7, driving glutamate-independent constitutive receptor activation that suppresses cAMP signaling by altering G protein activation kinetics, thereby setting a tonic low initial release probability and the characteristic facilitating behavior of these synapses [PMID:25047565, PMID:29686062, PMID:30940718]. The interaction is bidirectional and stabilizing: N-glycosylation of the partner receptor (mGluR7 or mGluR6) is required for stable ELFN1 binding and surface localization, and reciprocally ELFN1 localization depends on its receptor partner, as shown by loss and rescue of rod-spherule ELFN1 in mGluR6-null retina [PMID:32931036, PMID:39681475, PMID:40930976]. ELFN1 traffics to the membrane as an obligate LRR-mediated homodimer requiring a ~30-residue juxtamembranous intracellular motif [PMID:39675706]. Loss-of-function variants that block ELFN1 surface trafficking cause a human neurodevelopmental disorder with epilepsy, recapitulated by seizures, hyperactivity, and motor abnormalities in Elfn1-null mice and zebrafish [PMID:25047565, PMID:40576023]. ELFN1 also functions as a pharmacological context for mGluR7 modulator action, attenuating the maximal potentiation of mGluR7 positive allosteric modulators while preserving their activity at native synapses [PMID:40689847].","teleology":[{"year":2012,"claim":"Established that a postsynaptic interneuron-expressed molecule can dictate presynaptic release properties, defining a retrograde transsynaptic mechanism for building target-specific synapses.","evidence":"Cell-type-selective expression analysis plus loss-of-function in O-LM interneurons with electrophysiological readout of release probability","pmids":["23042292"],"confidence":"High","gaps":["Molecular partner mediating the retrograde signal not yet identified","No biochemical interaction defined"]},{"year":2013,"claim":"Mapped ELFN1 expression across interneuron and projection-neuron populations and demonstrated an in vivo requirement, linking its loss to seizures and behavioral abnormalities.","evidence":"β-galactosidase reporter knock-in expression mapping and behavioral phenotyping of knockout mice","pmids":["24312227"],"confidence":"Medium","gaps":["Molecular mechanism of phenotype unresolved","Single lab"]},{"year":2014,"claim":"Identified mGluR7 as the in-trans presynaptic partner that ELFN1 recruits, and connected the C-terminal recruitment region to human damaging mutations.","evidence":"Knockout mice, mGluR7 synaptic immunolocalization, presynaptic plasticity electrophysiology, and human mutation analysis","pmids":["25047565"],"confidence":"High","gaps":["Binding determinants not yet mapped to specific ectodomain regions","Effect on receptor signaling not biochemically characterized"]},{"year":2018,"claim":"Defined ELFN1 as a transsynaptic allosteric modulator with selectivity for all group III mGluRs and showed it directly reshapes G protein/cAMP signaling.","evidence":"Site-directed mutagenesis mapping two ectodomain binding sites; HEK293 transcellular reconstitution; BRET G protein kinetic assay","pmids":["29686062"],"confidence":"High","gaps":["Structural basis of the LRR–mGluR interface not resolved","Reconstituted in heterologous cells rather than native synapses"]},{"year":2019,"claim":"Demonstrated that ELFN1 drives constitutive, glutamate-independent mGluR7 activation by clustering, setting tonic low release probability at cortical pyr→SOM synapses.","evidence":"Cortical slice electrophysiology with pharmacological dissection and genetic loss-of-function for Elfn1 and mGluR7","pmids":["30940718"],"confidence":"High","gaps":["Layer-specific contribution of GluK2-KARs versus mGluR7 not fully separated","How clustering produces constitutive activity mechanistically unclear"]},{"year":2020,"claim":"Showed that receptor N-glycosylation is a prerequisite for ELFN1 binding, coupling mGluR7 maturation to stable transsynaptic complex formation.","evidence":"N-glycosylation site mutagenesis, fractionation, co-immunoprecipitation, and glycosylation inhibition in heterologous cells and neurons","pmids":["32931036"],"confidence":"Medium","gaps":["Single lab","Direct structural role of glycans in the binding interface not defined"]},{"year":2024,"claim":"Defined ELFN1 trafficking determinants, establishing that it reaches the membrane as an obligate LRR-mediated homodimer gated by a short intracellular motif.","evidence":"Domain deletion mutagenesis, biochemical fractionation, dimerization assays, and synaptic localization imaging","pmids":["39675706"],"confidence":"Medium","gaps":["Functional consequence of ELFN1/ELFN2 heterodimerization in vivo unknown","Single lab"]},{"year":2024,"claim":"Extended the glycosylation-dependent binding rule to mGluR6 and linked CSNB mutations to failed ELFN1 binding via defective Golgi glycosylation.","evidence":"Glycosylation analysis of mGluR6 CSNB mutants, co-IP with ELFN1, and bipolar cell immunolocalization","pmids":["39681475"],"confidence":"Medium","gaps":["Single lab","Causality between glycosylation and binding shown correlatively in mutants"]},{"year":2024,"claim":"Provided experimental evidence that ELFN1 acts outside the nervous system, influencing fibroblast morphology and motility in ECM models.","evidence":"Patient-derived ELFN1-mutant skin fibroblasts in in vitro and decellularized ECM models","pmids":["38986898"],"confidence":"Low","gaps":["No molecular mechanism identified beyond loss of expression","Single patient-derived model, not independently replicated"]},{"year":2025,"claim":"Localized the binding/trafficking function to the LRR-LRRCT module and demonstrated bidirectional mutual stabilization between ELFN1 and mGluR6 at rod spherules.","evidence":"ELFN1 deletion-construct binding assays, mGluR6-KO immunolocalization, and mGluR6-EGFP rescue in ON-bipolar cells","pmids":["40930976"],"confidence":"Medium","gaps":["Single lab","Atomic structure of the LRRCT–mGluR interface not determined"]},{"year":2025,"claim":"Confirmed ELFN1 loss-of-function as a Mendelian cause of neurodevelopmental disorder with epilepsy, tying the disease to defective ELFN1 surface trafficking.","evidence":"Whole-exome sequencing of multiple families, cell-surface trafficking assays, and Elfn1 KO mouse and zebrafish phenotyping","pmids":["40576023"],"confidence":"Medium","gaps":["Genotype–phenotype correlations across variant classes incomplete","Single study"]},{"year":2025,"claim":"Characterized how ELFN1 shapes the pharmacology of mGluR7 allosteric modulators, informing therapeutic targeting at native synapses.","evidence":"Transcellular mGluR7 signaling assays ± ELFN1 and slice electrophysiology at pyr→SOM synapses","pmids":["40689847"],"confidence":"Medium","gaps":["Single lab","Therapeutic relevance in disease models not tested"]},{"year":null,"claim":"The atomic structure of the ELFN1 LRR/LRRCT–group III mGluR complex and the mechanism by which trans-binding converts to constitutive G protein modulation remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the binding interface","Mechanistic link between clustering and constitutive receptor activity undefined","Non-neuronal ECM role lacks molecular mechanism"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[0,2]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,11]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[6,8,10]}],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[0,2,4]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[0,2]}],"complexes":[],"partners":["GRM7","GRM6","GRM4","GRM8","ELFN2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P0C7U0","full_name":"Protein ELFN1","aliases":["Extracellular leucine-rich repeat and fibronectin type-III domain-containing protein 1","Protein phosphatase 1 regulatory subunit 28"],"length_aa":828,"mass_kda":90.5,"function":"Postsynaptic protein that regulates circuit dynamics in the central nervous system by modulating the temporal dynamics of interneuron recruitment. Specifically present in excitatory synapses onto oriens-lacunosum molecular (OLM) interneurons and acts as a regulator of presynaptic release probability to direct the formation of highly facilitating pyramidal-OLM synapses (By similarity). Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes","subcellular_location":"Membrane; Cell projection, dendrite; Cell projection, axon","url":"https://www.uniprot.org/uniprotkb/P0C7U0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ELFN1","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ELFN1","total_profiled":1310},"omim":[{"mim_id":"621344","title":"DURSUN-OZGUL NEURODEVELOPMENTAL SYNDROME; DONDS","url":"https://www.omim.org/entry/621344"},{"mim_id":"614964","title":"EXTRACELLULAR LEUCINE-RICH REPEAT AND FIBRONECTIN TYPE III DOMAIN-CONTAINING PROTEIN 1; ELFN1","url":"https://www.omim.org/entry/614964"},{"mim_id":"308350","title":"DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 1; DEE1","url":"https://www.omim.org/entry/308350"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Cell Junctions","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"liver","ntpm":13.2}],"url":"https://www.proteinatlas.org/search/ELFN1"},"hgnc":{"alias_symbol":[],"prev_symbol":["PPP1R28"]},"alphafold":{"accession":"P0C7U0","domains":[{"cath_id":"3.80.10.10","chopping":"28-191","consensus_level":"high","plddt":91.6693,"start":28,"end":191},{"cath_id":"2.60.40.10","chopping":"319-400","consensus_level":"high","plddt":85.2883,"start":319,"end":400}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P0C7U0","model_url":"https://alphafold.ebi.ac.uk/files/AF-P0C7U0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P0C7U0-F1-predicted_aligned_error_v6.png","plddt_mean":61.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ELFN1","jax_strain_url":"https://www.jax.org/strain/search?query=ELFN1"},"sequence":{"accession":"P0C7U0","fasta_url":"https://rest.uniprot.org/uniprotkb/P0C7U0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P0C7U0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P0C7U0"}},"corpus_meta":[{"pmid":"35351858","id":"PMC_35351858","title":"Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer.","date":"2022","source":"Signal transduction and targeted therapy","url":"https://pubmed.ncbi.nlm.nih.gov/35351858","citation_count":143,"is_preprint":false},{"pmid":"23042292","id":"PMC_23042292","title":"Elfn1 regulates target-specific release probability at CA1-interneuron synapses.","date":"2012","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/23042292","citation_count":127,"is_preprint":false},{"pmid":"25047565","id":"PMC_25047565","title":"Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25047565","citation_count":98,"is_preprint":false},{"pmid":"29686062","id":"PMC_29686062","title":"Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors in 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oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38478184","citation_count":7,"is_preprint":false},{"pmid":"39681475","id":"PMC_39681475","title":"Defective glycosylation and ELFN1 binding of mGluR6 congenital stationary night blindness mutants.","date":"2024","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/39681475","citation_count":6,"is_preprint":false},{"pmid":"39675706","id":"PMC_39675706","title":"Distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, synaptic localization, and dimerization.","date":"2024","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/39675706","citation_count":5,"is_preprint":false},{"pmid":"36561847","id":"PMC_36561847","title":"lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB.","date":"2022","source":"Open medicine (Warsaw, Poland)","url":"https://pubmed.ncbi.nlm.nih.gov/36561847","citation_count":5,"is_preprint":false},{"pmid":"38037859","id":"PMC_38037859","title":"m6A-related lncRNAs as potential biomarkers and the lncRNA ELFN1-AS1/miR-182-5p/BCL-2 regulatory axis in diffuse large B-cell lymphoma.","date":"2023","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/38037859","citation_count":4,"is_preprint":false},{"pmid":"39528458","id":"PMC_39528458","title":"The long noncoding RNA ELFN1-AS1 promotes gastric cancer growth and metastasis by interacting with TAOK1 to inhibit the Hippo signaling pathway.","date":"2024","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/39528458","citation_count":4,"is_preprint":false},{"pmid":"38986898","id":"PMC_38986898","title":"ELFN1 is a new extracellular matrix (ECM)-associated protein.","date":"2024","source":"Life 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neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/40930976","citation_count":1,"is_preprint":false},{"pmid":"41535615","id":"PMC_41535615","title":"LncRNA ELFN1-AS1 maintains the stemness of colorectal cancer by preventing ubiquitinated degradation of the hnRNPA1 protein.","date":"2026","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/41535615","citation_count":1,"is_preprint":false},{"pmid":"38074639","id":"PMC_38074639","title":"Retraction: Long non-coding RNA ELFN1-AS1 promoted colon cancer cell growth and migration via the miR-191-5p/special AT-rich sequence-binding protein 1 axis.","date":"2023","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/38074639","citation_count":1,"is_preprint":false},{"pmid":"40689847","id":"PMC_40689847","title":"Profiling the Impact of mGlu7/Elfn1 Protein Interactions on the Pharmacology of mGlu7 Allosteric 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associations","date":"2024-09-24","source":"bioRxiv","url":"https://doi.org/10.1101/2024.09.23.24314219","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":21236,"output_tokens":3402,"usd":0.057369,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10872,"output_tokens":3757,"usd":0.074143,"stage2_stop_reason":"end_turn"},"total_usd":0.131512,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"ELFN1 is selectively expressed by hippocampal O-LM interneurons and, when expressed postsynaptically, regulates presynaptic release probability to direct the formation of highly facilitating (low release probability) pyramidal-O-LM synapses, demonstrating a retrograde transsynaptic signaling role.\",\n      \"method\": \"Selective expression analysis combined with loss-of-function in identified interneuron subtypes with electrophysiological readout of release probability\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean loss-of-function with defined synaptic phenotype, replicated across subsequent independent studies\",\n      \"pmids\": [\"23042292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Elfn1 is expressed in distinct subsets of hippocampal and cortical interneurons and also in axons of excitatory habenular neurons and long-range GABAergic globus pallidus neurons; Elfn1 mutant mice exhibit seizures, hyperactivity, and motor abnormalities reversible by amphetamine, establishing an in vivo functional requirement.\",\n      \"method\": \"β-galactosidase reporter knock-in expression analysis; behavioral phenotyping of knockout mice\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo KO with defined behavioral/neurological phenotype and detailed expression mapping; single lab\",\n      \"pmids\": [\"24312227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ELFN1 physically interacts in trans with presynaptic mGluR7, recruits mGluR7 to synaptic sites on somatostatin interneurons in the hippocampal CA1 stratum oriens and dentate gyrus, and is required for presynaptic plasticity at these synapses; loss of Elfn1 causes deficits in mGluR7 recruitment and results in hyperactivity and sensory-triggered epileptic seizures in mice. Damaging missense mutations of human ELFN1 cluster in the C-terminal region required for mGluR7 recruitment.\",\n      \"method\": \"Elfn1 knockout mice, immunolocalization of mGluR7 at synapses, electrophysiological assessment of presynaptic plasticity, human mutation analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal localization data, KO with defined synaptic and in vivo phenotype, replicated by independent labs\",\n      \"pmids\": [\"25047565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ELFN1 selectively binds all group III mGluRs (mGluR4, mGluR6, mGluR7, mGluR8) but not group I or II mGluRs; binding determinants were mapped to two distinct sites on the ELFN1 ectodomain by site-directed mutagenesis. In a transcellular signaling reconstitution assay in HEK293 cells, ELFN1 acts as a transsynaptic allosteric modulator that suppresses cAMP accumulation and alters both agonist-induced and constitutive group III mGluR activity by altering G protein activation kinetics, as measured by BRET.\",\n      \"method\": \"Site-directed mutagenesis; transcellular signaling reconstitution assay in HEK293 cells; BRET-based real-time kinetic G protein activation assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution in heterologous cells, mutagenesis mapping of binding sites, orthogonal BRET assay confirming G protein effect\",\n      \"pmids\": [\"29686062\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Elfn1 produces glutamate-independent (constitutive) activation of presynaptic mGluR7 through clustering at cortical pyramidal→somatostatin interneuron synapses, establishing a tonic low release probability. Facilitation at layer 2/3 synapses also depends on presynaptic GluK2-KARs, which can be engaged at layer 5 synapses via calmodulin activation, revealing layer-specific synaptic properties.\",\n      \"method\": \"Electrophysiology of cortical SOM interneuron synapses in mouse brain slices; pharmacological dissection; loss-of-function for Elfn1 and mGluR7\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — defined electrophysiological mechanism with pharmacological and genetic dissection, builds on replicated prior findings\",\n      \"pmids\": [\"30940718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"N-glycosylation of mGluR7 at four asparagine residues is essential for its forward trafficking and surface expression; deglycosylated mGluR7 is retained in the ER and degraded via the autophagolysosomal pathway. N-glycosylation of mGluR7 promotes its interaction with ELFN1, enabling proper localization and stable surface expression of mGluR7 at the presynaptic active zone.\",\n      \"method\": \"Mutagenesis of N-glycosylation sites; subcellular fractionation; co-immunoprecipitation of mGluR7 and ELFN1; pharmacological inhibition of glycosylation\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis and co-IP in heterologous cells and neurons; single lab, multiple orthogonal approaches\",\n      \"pmids\": [\"32931036\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The intracellular domain of ELFN1 (a ~30 amino acid juxtamembranous region) controls membrane trafficking and postsynaptic localization of ELFN1. ELFN1 exists as an obligate homodimer prior to membrane trafficking, with homodimerization mediated by the extracellular leucine-rich repeat (LRR) domain rather than the intracellular region. A single membrane-targeting motif in one protomer is sufficient for trafficking of the homodimer. ELFN2 exhibits similar properties and heterodimerizes with ELFN1.\",\n      \"method\": \"Domain deletion mutagenesis; biochemical fractionation; dimerization assays; synaptic localization imaging\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis with multiple functional readouts (trafficking, localization, dimerization), single lab\",\n      \"pmids\": [\"39675706\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CSNB-associated missense mutations in the extracellular ligand-binding domain of mGluR6 cause a trafficking defect leading to lack of complex N-glycosylation (suggesting Golgi bypass), failure to bind ELFN1, and mislocalization in bipolar cells, establishing that Golgi-acquired N-glycosylation of mGluR6 is required for its interaction with ELFN1 and correct synaptic targeting.\",\n      \"method\": \"Biochemical glycosylation analysis of mGluR6 mutants; co-immunoprecipitation binding assay with ELFN1; immunolocalization in bipolar cells\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple CSNB mutants tested with co-IP and localization; single lab, two orthogonal methods\",\n      \"pmids\": [\"39681475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The LRR and LRR C-terminal cap (LRRCT) regions of the ELFN1 extracellular domain are necessary and sufficient for binding to all group III mGluRs including mGluR6; deletion of the LRRCT domain abolishes trafficking of ELFN1 to rod photoreceptor spherules. In mGluR6-null mice, presynaptic ELFN1 localization in rod spherules is disrupted and rescued by re-expressing mGluR6-EGFP in ON-bipolar cells, demonstrating bidirectional transsynaptic mutual stabilization.\",\n      \"method\": \"In vitro binding assays with ELFN1 deletion constructs; immunolocalization in mGluR6 KO mice; mGluR6-EGFP rescue in ON-bipolar cells\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion mapping plus in vivo rescue experiment; single lab, orthogonal methods\",\n      \"pmids\": [\"40930976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ELFN1 is expressed in skin fibroblasts and its loss (due to signal-peptide frameshift mutation) dramatically alters fibroblast morphology, growth, proliferation, and motility in an in vitro ECM model, providing experimental evidence that ELFN1 participates in cell–ECM attachment outside the nervous system.\",\n      \"method\": \"Primary skin fibroblast isolation from ELFN1-mutated patients; in vitro ECM and decellularized ECM models; comparative morphological and motility analysis\",\n      \"journal\": \"Life sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single patient-derived cell model, no molecular mechanism identified beyond loss of ELFN1 expression\",\n      \"pmids\": [\"38986898\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Biallelic frameshift and in-frame deletion variants in ELFN1 disrupt ELFN1 protein trafficking to the cell surface (loss of function), causing a neurodevelopmental disorder with epilepsy in humans; Elfn1 loss in mice and zebrafish recapitulates motor abnormalities and seizures.\",\n      \"method\": \"Whole-exome sequencing of affected individuals; cell-surface trafficking assay for ELFN1 variants; behavioral/seizure phenotyping in Elfn1 KO mice and zebrafish\",\n      \"journal\": \"Genetics in medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional trafficking assay plus two orthologous animal models, multiple unrelated families; single study\",\n      \"pmids\": [\"40576023\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Positive allosteric modulators (PAMs) of mGluR7 show decreased maximal potentiation in the presence of ELFN1 but retain the ability to potentiate receptor signaling; negative allosteric modulators (NAMs) show similar efficacy with or without ELFN1. A tool PAM retains activity at pyramidal cell–somatostatin interneuron synapses where endogenous ELFN1 is expressed.\",\n      \"method\": \"Transcellular mGluR7 signaling assay in HEK293 cells ± ELFN1; electrophysiology at pyr→SOM synapses in brain slices\",\n      \"journal\": \"ACS chemical neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reconstituted pharmacology assay plus ex vivo slice electrophysiology; single lab, two orthogonal methods\",\n      \"pmids\": [\"40689847\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ELFN1 is a postsynaptic (and presynaptic in rods) transmembrane leucine-rich repeat/fibronectin III adhesion molecule that selectively recruits all group III mGluRs (mGluR4/6/7/8) via its extracellular LRR–LRRCT domain in trans, acts as a transsynaptic allosteric modulator suppressing G protein–cAMP signaling and driving constitutive, glutamate-independent mGluR7 activation that sets a low initial release probability at pyramidal→somatostatin interneuron synapses; its trafficking to the postsynaptic membrane requires a ~30 aa juxtamembranous intracellular motif and occurs as an obligate homodimer (dimerization via the LRR ectodomain), while N-glycosylation of its partner mGluR7/mGluR6 is required for stable ELFN1 binding and synaptic localization; loss of ELFN1 function in mice and humans causes impaired interneuron recruitment, epileptic seizures, hyperactivity, and a neurodevelopmental disorder.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ELFN1 is a postsynaptic transmembrane leucine-rich repeat adhesion molecule expressed by defined subsets of hippocampal and cortical interneurons that organizes target-specific synaptic properties through retrograde transsynaptic signaling [#0, #1]. It physically engages presynaptic group III metabotropic glutamate receptors in trans — binding mGluR4, mGluR6, mGluR7, and mGluR8 but not group I or II mGluRs — via its extracellular LRR/LRRCT module, which is necessary and sufficient for receptor binding and for ELFN1's own synaptic trafficking [#3, #8]. At pyramidal→somatostatin interneuron synapses ELFN1 recruits and clusters mGluR7, driving glutamate-independent constitutive receptor activation that suppresses cAMP signaling by altering G protein activation kinetics, thereby setting a tonic low initial release probability and the characteristic facilitating behavior of these synapses [#2, #3, #4]. The interaction is bidirectional and stabilizing: N-glycosylation of the partner receptor (mGluR7 or mGluR6) is required for stable ELFN1 binding and surface localization, and reciprocally ELFN1 localization depends on its receptor partner, as shown by loss and rescue of rod-spherule ELFN1 in mGluR6-null retina [#5, #7, #8]. ELFN1 traffics to the membrane as an obligate LRR-mediated homodimer requiring a ~30-residue juxtamembranous intracellular motif [#6]. Loss-of-function variants that block ELFN1 surface trafficking cause a human neurodevelopmental disorder with epilepsy, recapitulated by seizures, hyperactivity, and motor abnormalities in Elfn1-null mice and zebrafish [#2, #10]. ELFN1 also functions as a pharmacological context for mGluR7 modulator action, attenuating the maximal potentiation of mGluR7 positive allosteric modulators while preserving their activity at native synapses [#11].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established that a postsynaptic interneuron-expressed molecule can dictate presynaptic release properties, defining a retrograde transsynaptic mechanism for building target-specific synapses.\",\n      \"evidence\": \"Cell-type-selective expression analysis plus loss-of-function in O-LM interneurons with electrophysiological readout of release probability\",\n      \"pmids\": [\"23042292\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular partner mediating the retrograde signal not yet identified\", \"No biochemical interaction defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mapped ELFN1 expression across interneuron and projection-neuron populations and demonstrated an in vivo requirement, linking its loss to seizures and behavioral abnormalities.\",\n      \"evidence\": \"β-galactosidase reporter knock-in expression mapping and behavioral phenotyping of knockout mice\",\n      \"pmids\": [\"24312227\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of phenotype unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified mGluR7 as the in-trans presynaptic partner that ELFN1 recruits, and connected the C-terminal recruitment region to human damaging mutations.\",\n      \"evidence\": \"Knockout mice, mGluR7 synaptic immunolocalization, presynaptic plasticity electrophysiology, and human mutation analysis\",\n      \"pmids\": [\"25047565\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Binding determinants not yet mapped to specific ectodomain regions\", \"Effect on receptor signaling not biochemically characterized\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined ELFN1 as a transsynaptic allosteric modulator with selectivity for all group III mGluRs and showed it directly reshapes G protein/cAMP signaling.\",\n      \"evidence\": \"Site-directed mutagenesis mapping two ectodomain binding sites; HEK293 transcellular reconstitution; BRET G protein kinetic assay\",\n      \"pmids\": [\"29686062\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the LRR–mGluR interface not resolved\", \"Reconstituted in heterologous cells rather than native synapses\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated that ELFN1 drives constitutive, glutamate-independent mGluR7 activation by clustering, setting tonic low release probability at cortical pyr→SOM synapses.\",\n      \"evidence\": \"Cortical slice electrophysiology with pharmacological dissection and genetic loss-of-function for Elfn1 and mGluR7\",\n      \"pmids\": [\"30940718\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Layer-specific contribution of GluK2-KARs versus mGluR7 not fully separated\", \"How clustering produces constitutive activity mechanistically unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showed that receptor N-glycosylation is a prerequisite for ELFN1 binding, coupling mGluR7 maturation to stable transsynaptic complex formation.\",\n      \"evidence\": \"N-glycosylation site mutagenesis, fractionation, co-immunoprecipitation, and glycosylation inhibition in heterologous cells and neurons\",\n      \"pmids\": [\"32931036\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Direct structural role of glycans in the binding interface not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined ELFN1 trafficking determinants, establishing that it reaches the membrane as an obligate LRR-mediated homodimer gated by a short intracellular motif.\",\n      \"evidence\": \"Domain deletion mutagenesis, biochemical fractionation, dimerization assays, and synaptic localization imaging\",\n      \"pmids\": [\"39675706\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of ELFN1/ELFN2 heterodimerization in vivo unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended the glycosylation-dependent binding rule to mGluR6 and linked CSNB mutations to failed ELFN1 binding via defective Golgi glycosylation.\",\n      \"evidence\": \"Glycosylation analysis of mGluR6 CSNB mutants, co-IP with ELFN1, and bipolar cell immunolocalization\",\n      \"pmids\": [\"39681475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Causality between glycosylation and binding shown correlatively in mutants\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Provided experimental evidence that ELFN1 acts outside the nervous system, influencing fibroblast morphology and motility in ECM models.\",\n      \"evidence\": \"Patient-derived ELFN1-mutant skin fibroblasts in in vitro and decellularized ECM models\",\n      \"pmids\": [\"38986898\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No molecular mechanism identified beyond loss of expression\", \"Single patient-derived model, not independently replicated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Localized the binding/trafficking function to the LRR-LRRCT module and demonstrated bidirectional mutual stabilization between ELFN1 and mGluR6 at rod spherules.\",\n      \"evidence\": \"ELFN1 deletion-construct binding assays, mGluR6-KO immunolocalization, and mGluR6-EGFP rescue in ON-bipolar cells\",\n      \"pmids\": [\"40930976\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Atomic structure of the LRRCT–mGluR interface not determined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Confirmed ELFN1 loss-of-function as a Mendelian cause of neurodevelopmental disorder with epilepsy, tying the disease to defective ELFN1 surface trafficking.\",\n      \"evidence\": \"Whole-exome sequencing of multiple families, cell-surface trafficking assays, and Elfn1 KO mouse and zebrafish phenotyping\",\n      \"pmids\": [\"40576023\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Genotype–phenotype correlations across variant classes incomplete\", \"Single study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Characterized how ELFN1 shapes the pharmacology of mGluR7 allosteric modulators, informing therapeutic targeting at native synapses.\",\n      \"evidence\": \"Transcellular mGluR7 signaling assays ± ELFN1 and slice electrophysiology at pyr→SOM synapses\",\n      \"pmids\": [\"40689847\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Therapeutic relevance in disease models not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The atomic structure of the ELFN1 LRR/LRRCT–group III mGluR complex and the mechanism by which trans-binding converts to constitutive G protein modulation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the binding interface\", \"Mechanistic link between clustering and constitutive receptor activity undefined\", \"Non-neuronal ECM role lacks molecular mechanism\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 11]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [6, 8, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GRM7\", \"GRM6\", \"GRM4\", \"GRM8\", \"ELFN2\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}