{"gene":"EGFLAM","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2026,"finding":"Homozygous loss-of-function variants in EGFLAM (frameshift c.1563_1566del and nonsense c.1795C>T) cause complete congenital stationary night blindness (cCSNB) with ON-bipolar cell dysfunction, as demonstrated by electronegative Schubert-Bornschein ffERG pattern in affected patients; the EGFLAM protein localizes to the outer plexiform layer of the retina and is required for ON-bipolar cell signaling.","method":"Exome sequencing, genome sequencing, Sanger sequencing, cosegregation analysis, full-field electroretinography (ffERG) in human patients","journal":"JAMA ophthalmology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — human genetic evidence with cosegregation in two unrelated families, ffERG functional readout; single study, no in vitro reconstitution or model organism validation in this paper","pmids":["41343198"],"is_preprint":false}],"current_model":"EGFLAM encodes a protein that localizes to the outer plexiform layer of the retina, where it is required for ON-bipolar cell signaling; biallelic loss-of-function variants cause complete congenital stationary night blindness, establishing EGFLAM as a component of the retinal ON-pathway synaptic machinery."},"narrative":{"mechanistic_narrative":"EGFLAM encodes a protein localized to the outer plexiform layer of the retina that is required for ON-bipolar cell signaling [PMID:41343198]. Biallelic loss-of-function variants (frameshift and nonsense) cause complete congenital stationary night blindness (cCSNB), with affected patients showing an electronegative Schubert-Bornschein full-field electroretinogram pattern indicative of ON-bipolar cell dysfunction [PMID:41343198]. Beyond this genetic and localization evidence, no further molecular mechanism, binding partners, or biochemical activity for EGFLAM has been characterized in the available corpus.","teleology":[{"year":2026,"claim":"Establishing the genetic and physiological role of EGFLAM in vision, this work showed that biallelic loss of EGFLAM disrupts the retinal ON-pathway and causes a defined inherited disorder.","evidence":"Exome/genome/Sanger sequencing with cosegregation in two unrelated families and ffERG functional readout in human patients, plus retinal localization to the outer plexiform layer","pmids":["41343198"],"confidence":"Medium","gaps":["No in vitro reconstitution or model-organism validation in this study","Molecular partners and biochemical activity of EGFLAM at the photoreceptor-to-bipolar synapse are undefined","Mechanism by which EGFLAM supports ON-bipolar signal transmission is unknown"]},{"year":null,"claim":"How EGFLAM functions at the outer plexiform layer synapse — its direct binding partners, biochemical activity, and the molecular step it contributes to ON-bipolar signaling — remains unresolved.","evidence":"No timeline discovery addresses EGFLAM molecular activity or interactions","pmids":[],"confidence":"Medium","gaps":["No direct physical partners identified","No biochemical or structural characterization","No animal model phenotype reported in the corpus"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q63HQ2","full_name":"Pikachurin","aliases":["Agrin-like protein","EGF-like, fibronectin type-III and laminin G-like domain-containing protein"],"length_aa":1017,"mass_kda":111.3,"function":"Involved in both the retinal photoreceptor ribbon synapse formation and physiological functions of visual perception. Plays a key role in the synaptic organization of photoreceptors by mediating transsynaptic interaction between alpha-dystroglycan and GPR179 on the postsynaptic membrane. Necessary for proper bipolar dendritic tip apposition to the photoreceptor ribbon synapse. Promotes matrix assembly and cell adhesiveness","subcellular_location":"Secreted, extracellular space, extracellular matrix; Synaptic cleft; Presynaptic active zone","url":"https://www.uniprot.org/uniprotkb/Q63HQ2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EGFLAM","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/EGFLAM","total_profiled":1310},"omim":[{"mim_id":"617683","title":"EGF-LIKE, FIBRONECTIN TYPE III, AND LAMININ G DOMAINS-CONTAINING PROTEIN; EGFLAM","url":"https://www.omim.org/entry/617683"},{"mim_id":"128239","title":"DYSTROGLYCAN 1; DAG1","url":"https://www.omim.org/entry/128239"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"tongue","ntpm":113.3}],"url":"https://www.proteinatlas.org/search/EGFLAM"},"hgnc":{"alias_symbol":["FLJ39155","AGRINL","AGRNL","PIKA"],"prev_symbol":[]},"alphafold":{"accession":"Q63HQ2","domains":[{"cath_id":"2.60.40.10","chopping":"40-139","consensus_level":"high","plddt":82.4792,"start":40,"end":139},{"cath_id":"2.60.40.10","chopping":"147-236","consensus_level":"high","plddt":84.5874,"start":147,"end":236},{"cath_id":"2.60.120.200","chopping":"390-564","consensus_level":"high","plddt":92.2265,"start":390,"end":564},{"cath_id":"2.10.25.10","chopping":"568-603","consensus_level":"medium","plddt":93.785,"start":568,"end":603},{"cath_id":"2.60.120.200","chopping":"607-786","consensus_level":"high","plddt":91.2517,"start":607,"end":786},{"cath_id":"2.10.25.10","chopping":"789-822","consensus_level":"medium","plddt":89.5512,"start":789,"end":822},{"cath_id":"2.60.120.200","chopping":"839-1014","consensus_level":"high","plddt":90.0266,"start":839,"end":1014}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q63HQ2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q63HQ2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q63HQ2-F1-predicted_aligned_error_v6.png","plddt_mean":80.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EGFLAM","jax_strain_url":"https://www.jax.org/strain/search?query=EGFLAM"},"sequence":{"accession":"Q63HQ2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q63HQ2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q63HQ2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q63HQ2"}},"corpus_meta":[{"pmid":"27512391","id":"PMC_27512391","title":"Diet Diversity Is Associated with Beta but not Alpha Diversity of Pika Gut Microbiota.","date":"2016","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27512391","citation_count":143,"is_preprint":false},{"pmid":"15862582","id":"PMC_15862582","title":"Echinococcus shiquicus n. sp., a taeniid cestode from Tibetan fox and plateau pika in China.","date":"2005","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15862582","citation_count":132,"is_preprint":false},{"pmid":"19663994","id":"PMC_19663994","title":"When cold is better: climate-driven elevation shifts yield complex patterns of diversification and demography in an alpine specialist (American pika, Ochotona princeps).","date":"2009","source":"Evolution; 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Part A, Molecular & integrative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/25988712","citation_count":4,"is_preprint":false},{"pmid":"30680105","id":"PMC_30680105","title":"Noninvasive sampling reveals population genetic structure in the Royle's pika, Ochotona roylei, in the western Himalaya.","date":"2018","source":"Ecology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/30680105","citation_count":4,"is_preprint":false},{"pmid":"29995897","id":"PMC_29995897","title":"Identification of a contact zone and hybridization for two subspecies of the American pika (Ochotona princeps) within a single protected area.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/29995897","citation_count":4,"is_preprint":false},{"pmid":"37802756","id":"PMC_37802756","title":"Disrupted circadian rhythms in the plateau pika.","date":"2023","source":"Trends in neurosciences","url":"https://pubmed.ncbi.nlm.nih.gov/37802756","citation_count":3,"is_preprint":false},{"pmid":"39684491","id":"PMC_39684491","title":"Plateau Pika Disturbance Changes Soil Bacterial Functions and Exoenzyme Abundance to Modulate the C Cycle Pathway in Alpine Grasslands.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39684491","citation_count":3,"is_preprint":false},{"pmid":"32100704","id":"PMC_32100704","title":"Agromyces badenianii sp. nov., isolated from plateau pika (Ochotona curzoniae).","date":"2020","source":"International journal of systematic and evolutionary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32100704","citation_count":3,"is_preprint":false},{"pmid":"36139230","id":"PMC_36139230","title":"Vitamin D3 Metabolic Enzymes in Plateau Zokor (Myospalax baileyi) and Plateau Pika (Ochotona curzoniae): Expression and Response to Hypoxia.","date":"2022","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/36139230","citation_count":3,"is_preprint":false},{"pmid":"39269902","id":"PMC_39269902","title":"A nature-inspired HIF stabilizer derived from a highland-adaptation insertion of plateau pika Epas1 protein.","date":"2024","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/39269902","citation_count":3,"is_preprint":false},{"pmid":"33200238","id":"PMC_33200238","title":"Vector-Borne Pathogens in Ectoparasites Collected from High-Elevation Pika Populations.","date":"2020","source":"EcoHealth","url":"https://pubmed.ncbi.nlm.nih.gov/33200238","citation_count":3,"is_preprint":false},{"pmid":"37931840","id":"PMC_37931840","title":"The genomic characteristics and pathogenicity of a mammalian orthoreovirus within a new lineage from wild pika in plateau.","date":"2023","source":"Virologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/37931840","citation_count":3,"is_preprint":false},{"pmid":"37821317","id":"PMC_37821317","title":"Potential option for rabies post-exposure prophylaxis: New vaccine with PIKA adjuvant against diverse Chinese rabies strains.","date":"2023","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/37821317","citation_count":3,"is_preprint":false},{"pmid":"38533117","id":"PMC_38533117","title":"The first complete mitochondrial genome data of the Afghan pika Ochotona rufescens (Lagomorpha, Ochotonidae), near the type locality.","date":"2024","source":"Data in brief","url":"https://pubmed.ncbi.nlm.nih.gov/38533117","citation_count":3,"is_preprint":false},{"pmid":"20451163","id":"PMC_20451163","title":"A modified enrichment method to construct microsatellite library from plateau pika genome (Ochotona curzoniae).","date":"2010","source":"Genomics, proteomics & bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/20451163","citation_count":3,"is_preprint":false},{"pmid":"28261461","id":"PMC_28261461","title":"Variation in subsurface thermal characteristics of microrefuges used by range core and peripheral populations of the American pika (Ochotona princeps).","date":"2017","source":"Ecology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/28261461","citation_count":3,"is_preprint":false},{"pmid":"38672421","id":"PMC_38672421","title":"Dysbiosis of Gut Microbiome Aggravated Male Infertility in Captivity of Plateau Pika.","date":"2024","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/38672421","citation_count":2,"is_preprint":false},{"pmid":"37112739","id":"PMC_37112739","title":"IgG1-Dominant Antibody Response Induced by Recombinant Trimeric SARS-CoV-2 Spike Protein with PIKA Adjuvant.","date":"2023","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/37112739","citation_count":2,"is_preprint":false},{"pmid":"36830427","id":"PMC_36830427","title":"A Comparative Study on the Distribution Pattern of Endocrine Cells in the Gastrointestinal Tract of Two Small Alpine Mammals, Plateau Zokor (Eospalax baileyi) and Plateau Pika (Ochotona curzoniae).","date":"2023","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/36830427","citation_count":2,"is_preprint":false},{"pmid":"37604894","id":"PMC_37604894","title":"Ancient DNA re-opens the question of the phylogenetic position of the Sardinian pika Prolagus sardus (Wagner, 1829), an extinct lagomorph.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37604894","citation_count":2,"is_preprint":false},{"pmid":"40334979","id":"PMC_40334979","title":"Evolutionary divergence on the Qinghai-Xizang Plateau: How life-history traits shape the diversity of plateau zokor and pika populations.","date":"2025","source":"Journal of genetics and genomics = Yi chuan xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/40334979","citation_count":2,"is_preprint":false},{"pmid":"26109304","id":"PMC_26109304","title":"[The expression of the sperm-specific lactate dehydrogenase gene Ldh-c in plateau pika (Ochotona curzoniae) cardiac muscle and its effect on the anaerobic glycolysis].","date":"2015","source":"Sheng li xue bao : [Acta physiologica Sinica]","url":"https://pubmed.ncbi.nlm.nih.gov/26109304","citation_count":2,"is_preprint":false},{"pmid":"33474343","id":"PMC_33474343","title":"The complete mitochondrial DNA sequence of the Chinese red pika (Ochotona erythrotis).","date":"2018","source":"Mitochondrial DNA. Part B, Resources","url":"https://pubmed.ncbi.nlm.nih.gov/33474343","citation_count":2,"is_preprint":false},{"pmid":"39425616","id":"PMC_39425616","title":"Evidence of Intraspecific Adaptive Variation in the American Pika (Ochotona princeps) on a Continental Scale Using a Target Enrichment and Mitochondrial Genome Skimming Approach.","date":"2024","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/39425616","citation_count":2,"is_preprint":false},{"pmid":"24130861","id":"PMC_24130861","title":"An intriguing shift occurs in the novel protein phosphatase 1 binding partner, TCTEX1D4: evidence of positive selection in a pika model.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24130861","citation_count":2,"is_preprint":false},{"pmid":"41343198","id":"PMC_41343198","title":"EGFLAM Pathogenic Variants and Congenital Stationary Night Blindness.","date":"2026","source":"JAMA ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/41343198","citation_count":1,"is_preprint":false},{"pmid":"39525677","id":"PMC_39525677","title":"Safety, tolerability, and immunogenicity of PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine in healthy adults: an open-label randomized phase I clinical trial.","date":"2024","source":"Clinical and experimental vaccine research","url":"https://pubmed.ncbi.nlm.nih.gov/39525677","citation_count":1,"is_preprint":false},{"pmid":"39361517","id":"PMC_39361517","title":"Adlercreutzia wanghongyangiae sp. nov., and Adlercreutzia shanghongiae sp. nov., two new members of the genus Adlercreutzia isolated from plateau pika (Ochotona curzoniae).","date":"2024","source":"International journal of systematic and evolutionary microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/39361517","citation_count":1,"is_preprint":false},{"pmid":"39563190","id":"PMC_39563190","title":"Complete mitochondrial genome of Scathophaga stercoraria (Diptera: Scathophagidae) in wild plateau pika: genome descriptions and phylogenetic evolution.","date":"2024","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/39563190","citation_count":1,"is_preprint":false},{"pmid":"17984595","id":"PMC_17984595","title":"Molecular cloning and tissue distribution of uncoupling protein 1 (UCP1) in plateau pika (Ochotona dauurica).","date":"2007","source":"The Journal of veterinary medical science","url":"https://pubmed.ncbi.nlm.nih.gov/17984595","citation_count":1,"is_preprint":false},{"pmid":"36506315","id":"PMC_36506315","title":"Transcriptome analysis of pika heart tissue reveals mechanisms underlying the adaptation of a keystone species on the roof of the world.","date":"2022","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/36506315","citation_count":1,"is_preprint":false},{"pmid":"25842833","id":"PMC_25842833","title":"[Cloning and characterization of lactate dehydrogenase C4 from pika ochotona curzoniae].","date":"2014","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/25842833","citation_count":1,"is_preprint":false},{"pmid":"21171414","id":"PMC_21171414","title":"[The changes of function and morphology of pulmonary arterial vessels in the pika at high altitude].","date":"2001","source":"Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology","url":"https://pubmed.ncbi.nlm.nih.gov/21171414","citation_count":1,"is_preprint":false},{"pmid":"39525672","id":"PMC_39525672","title":"Safety and immunogenicity of PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine as a booster against SARS-CoV-2: a phase II, open-label, randomized, double-blinded study.","date":"2024","source":"Clinical and experimental vaccine research","url":"https://pubmed.ncbi.nlm.nih.gov/39525672","citation_count":0,"is_preprint":false},{"pmid":"41004966","id":"PMC_41004966","title":"Ecological restoration in plateau pika-disturbed alpine meadows: Soil-microbe-enzyme stoichiometry and microbial adaptations during vegetation recovery of bare patches.","date":"2025","source":"Journal of environmental management","url":"https://pubmed.ncbi.nlm.nih.gov/41004966","citation_count":0,"is_preprint":false},{"pmid":"41387927","id":"PMC_41387927","title":"Deoxycholic acid derived from the gut microbiota involved in the regulation of adaptive thermogenesis in response to dietary protein restriction in plateau pika.","date":"2025","source":"Microbiome","url":"https://pubmed.ncbi.nlm.nih.gov/41387927","citation_count":0,"is_preprint":false},{"pmid":"40216611","id":"PMC_40216611","title":"Long-term effects of grazing exclosure and plateau pika disturbance on soil biochemistry in alpine meadows.","date":"2025","source":"Environmental monitoring and assessment","url":"https://pubmed.ncbi.nlm.nih.gov/40216611","citation_count":0,"is_preprint":false},{"pmid":"41845197","id":"PMC_41845197","title":"Genetic recovery in an alpine climate-sensitive pika species during upward treeline shift.","date":"2026","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41845197","citation_count":0,"is_preprint":false},{"pmid":"41545957","id":"PMC_41545957","title":"Genome assembly of Helan Shan pika (Ochotona argentata): a key resource for endangered species conservation.","date":"2026","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41545957","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":52617,"output_tokens":875,"usd":0.085488,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6619,"output_tokens":852,"usd":0.027197,"stage2_stop_reason":"end_turn"},"total_usd":0.112685,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the 100 papers, I need to identify which ones are actually about the human/mammalian gene EGFLAM (also known as FLJ39155, AGRINL, AGRNL, PIKA).\n\nThe vast majority of papers are about the animal \"pika\" (Ochotona species) — these are symbol collisions. The HGNC alias \"PIKA\" for EGFLAM refers to the protein, not the animal.\n\nPapers about PIKA adjuvant (a dsRNA/polyI:C analog used in vaccines) — these are also not about the EGFLAM protein.\n\nPaper [4] about \"PIKA antigens\" in nuclear domains — this refers to a nuclear antigen called PIKA (Polymorphic Interphase Karyosomal Association), not the EGFLAM protein.\n\nPaper [29] (PMID:28339009) — This is an EWAS study identifying EGFLAM as a susceptibility locus for aortic aneurysm. This is a genetic association study, not a mechanistic finding. EXCLUDE.\n\nPaper [87] (PMID:41343198) — This describes EGFLAM pathogenic variants causing congenital stationary night blindness (cCSNB). It mentions that \"The corresponding protein is localized in the outer plexiform layer and important for ON-bipolar cell signaling in the retina.\" This is a clinical genetics paper that includes localization information and functional context for EGFLAM in the retina, established through patient phenotyping and genetic analysis. The localization in the outer plexiform layer and role in ON-bipolar cell signaling appears to be referenced as established prior knowledge rather than a new experiment in this paper. This paper identifies pathogenic variants and their clinical consequence but the mechanistic statement about localization is cited as background knowledge.\n\nGiven the extremely sparse mechanistic data in this corpus specifically about EGFLAM protein function, only paper [87] is truly about the canonical EGFLAM gene, and it provides clinical genetic evidence linking EGFLAM variants to cCSNB with reference to its retinal localization and ON-bipolar cell signaling role.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2026,\n      \"finding\": \"Homozygous loss-of-function variants in EGFLAM (frameshift c.1563_1566del and nonsense c.1795C>T) cause complete congenital stationary night blindness (cCSNB) with ON-bipolar cell dysfunction, as demonstrated by electronegative Schubert-Bornschein ffERG pattern in affected patients; the EGFLAM protein localizes to the outer plexiform layer of the retina and is required for ON-bipolar cell signaling.\",\n      \"method\": \"Exome sequencing, genome sequencing, Sanger sequencing, cosegregation analysis, full-field electroretinography (ffERG) in human patients\",\n      \"journal\": \"JAMA ophthalmology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — human genetic evidence with cosegregation in two unrelated families, ffERG functional readout; single study, no in vitro reconstitution or model organism validation in this paper\",\n      \"pmids\": [\"41343198\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"EGFLAM encodes a protein that localizes to the outer plexiform layer of the retina, where it is required for ON-bipolar cell signaling; biallelic loss-of-function variants cause complete congenital stationary night blindness, establishing EGFLAM as a component of the retinal ON-pathway synaptic machinery.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EGFLAM encodes a protein localized to the outer plexiform layer of the retina that is required for ON-bipolar cell signaling [#0]. Biallelic loss-of-function variants (frameshift and nonsense) cause complete congenital stationary night blindness (cCSNB), with affected patients showing an electronegative Schubert-Bornschein full-field electroretinogram pattern indicative of ON-bipolar cell dysfunction [#0]. Beyond this genetic and localization evidence, no further molecular mechanism, binding partners, or biochemical activity for EGFLAM has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2026,\n      \"claim\": \"Establishing the genetic and physiological role of EGFLAM in vision, this work showed that biallelic loss of EGFLAM disrupts the retinal ON-pathway and causes a defined inherited disorder.\",\n      \"evidence\": \"Exome/genome/Sanger sequencing with cosegregation in two unrelated families and ffERG functional readout in human patients, plus retinal localization to the outer plexiform layer\",\n      \"pmids\": [\"41343198\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Single human genetic study without in vitro reconstitution or model-organism validation\",\n      \"gaps\": [\n        \"No in vitro reconstitution or model-organism validation in this study\",\n        \"Molecular partners and biochemical activity of EGFLAM at the photoreceptor-to-bipolar synapse are undefined\",\n        \"Mechanism by which EGFLAM supports ON-bipolar signal transmission is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How EGFLAM functions at the outer plexiform layer synapse — its direct binding partners, biochemical activity, and the molecular step it contributes to ON-bipolar signaling — remains unresolved.\",\n      \"evidence\": \"No timeline discovery addresses EGFLAM molecular activity or interactions\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct physical partners identified\",\n        \"No biochemical or structural characterization\",\n        \"No animal model phenotype reported in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":2,"faith_pct":100.0}}