{"gene":"EEIG2","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2025,"finding":"FAM102B (EEIG2) acts as an adaptor protein that mediates binding of the bridge-like lipid transfer protein BLTP2 to the plasma membrane at ER-PM contact sites, alongside phosphoinositides and N-BAR domain proteins.","method":"Interaction mapping / localization studies identifying FAM102B as a binding partner of BLTP2 at ER-PM contacts; loss-of-function showing accumulation of intracellular vacuoles connected to the PM.","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, interaction identified but abstract does not detail orthogonal methods (e.g., mutagenesis or reconstitution) for FAM102B specifically; functional consequence (vacuole accumulation) is attributed to BLTP2 loss, not FAM102B loss directly.","pmids":["40899996"],"is_preprint":false},{"year":2025,"finding":"FAM102B (EEIG2) acts as an adaptor protein that mediates binding of BLTP2 to the plasma membrane at ER-PM contact sites, contributing to ER tethering at tubular endosomes that become continuous with the PM and at macropinosomes fusing with the PM.","method":"Interaction mapping and localization studies in cell-based systems identifying FAM102B as a BLTP2 binding partner at membrane contact sites (preprint version of the peer-reviewed paper).","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, preprint; interaction identified but abstract lacks detail on orthogonal validation methods for FAM102B specifically; consistent with the peer-reviewed publication.","pmids":["39974967"],"is_preprint":true}],"current_model":"FAM102B (EEIG2) functions as an adaptor protein at ER-plasma membrane contact sites, where it interacts with the bridge-like lipid transfer protein BLTP2 to mediate ER tethering to the plasma membrane and support bulk lipid transport, thereby contributing to plasma membrane dynamics."},"narrative":{"mechanistic_narrative":"EEIG2 (FAM102B) functions as an adaptor protein at ER–plasma membrane contact sites, where it mediates recruitment of the bridge-like lipid transfer protein BLTP2 to the plasma membrane alongside phosphoinositides and N-BAR domain proteins [PMID:40899996]. Through this interaction, EEIG2 contributes to ER tethering to the plasma membrane, supporting membrane contact at sites of bulk lipid transport [PMID:40899996]. Beyond its role as a BLTP2 adaptor at these contact sites, no further mechanistic detail for EEIG2 has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Whether FAM102B/EEIG2 had a defined molecular role was unknown; identifying it as a BLTP2 binding partner at ER-PM contacts established it as an adaptor coupling a bridge-like lipid transfer protein to the plasma membrane.","evidence":"Interaction mapping and localization in cell-based systems, with loss-of-function showing PM-connected intracellular vacuole accumulation (peer-reviewed)","pmids":["40899996"],"confidence":"Medium","gaps":["No orthogonal validation (mutagenesis or reconstitution) for the FAM102B-BLTP2 interaction specifically","Vacuole accumulation phenotype attributed to BLTP2 loss, not directly to FAM102B loss","Mechanism by which FAM102B engages the PM (lipid vs protein determinants) not defined"]},{"year":2025,"claim":"The preprint extended the adaptor model by placing FAM102B-mediated BLTP2 tethering at tubular endosomes continuous with the PM and at macropinosomes fusing with the PM, broadening the membrane contexts where it operates.","evidence":"Interaction mapping and localization in cell-based systems (preprint)","pmids":["39974967"],"confidence":"Medium","gaps":["Preprint without detailed orthogonal validation for FAM102B","Direct demonstration of lipid transport dependence on FAM102B not shown","Stoichiometry and structural basis of the BLTP2 interaction unresolved"]},{"year":null,"claim":"How FAM102B selects and stabilizes specific contact-site geometries, and whether its adaptor function is required for bulk lipid transport itself, remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct loss-of-function phenotype attributed specifically to FAM102B","No structural or biochemical reconstitution of the FAM102B-BLTP2-PM assembly","Physiological consequences of FAM102B loss at the organism level uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0]}],"complexes":[],"partners":["BLTP2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5T8I3","full_name":"EEIG family member 2","aliases":[],"length_aa":360,"mass_kda":39.3,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q5T8I3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EEIG2","classification":"Not Classified","n_dependent_lines":26,"n_total_lines":1208,"dependency_fraction":0.02152317880794702},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/EEIG2","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"FAM102B","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FAM102B"},"hgnc":{"alias_symbol":["DKFZp779B126","SYM-3B"],"prev_symbol":["FAM102B"]},"alphafold":{"accession":"Q5T8I3","domains":[{"cath_id":"2.60.40.150","chopping":"3-143","consensus_level":"high","plddt":91.9708,"start":3,"end":143},{"cath_id":"-","chopping":"328-360","consensus_level":"medium","plddt":73.2818,"start":328,"end":360}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T8I3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T8I3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q5T8I3-F1-predicted_aligned_error_v6.png","plddt_mean":70.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EEIG2","jax_strain_url":"https://www.jax.org/strain/search?query=EEIG2"},"sequence":{"accession":"Q5T8I3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5T8I3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5T8I3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5T8I3"}},"corpus_meta":[{"pmid":"31280933","id":"PMC_31280933","title":"Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study.","date":"2019","source":"Journal of autoimmunity","url":"https://pubmed.ncbi.nlm.nih.gov/31280933","citation_count":45,"is_preprint":false},{"pmid":"40899996","id":"PMC_40899996","title":"Multiple interactions recruit BLTP2 to ER-PM contacts to control plasma membrane dynamics.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/40899996","citation_count":6,"is_preprint":false},{"pmid":"40711007","id":"PMC_40711007","title":"Population Cohort-Validated PM2.5-Induced Gene Signatures: A Machine Learning Approach to Individual Exposure Prediction.","date":"2025","source":"Toxics","url":"https://pubmed.ncbi.nlm.nih.gov/40711007","citation_count":1,"is_preprint":false},{"pmid":"39974967","id":"PMC_39974967","title":"Multiple interactions mediate the localization of BLTP2 at ER-PM contacts to control plasma membrane dynamics.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39974967","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3982,"output_tokens":585,"usd":0.01036,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6947,"output_tokens":1285,"usd":0.03343,"stage2_stop_reason":"end_turn"},"total_usd":0.04379,"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\": 2025,\n      \"finding\": \"FAM102B (EEIG2) acts as an adaptor protein that mediates binding of the bridge-like lipid transfer protein BLTP2 to the plasma membrane at ER-PM contact sites, alongside phosphoinositides and N-BAR domain proteins.\",\n      \"method\": \"Interaction mapping / localization studies identifying FAM102B as a binding partner of BLTP2 at ER-PM contacts; loss-of-function showing accumulation of intracellular vacuoles connected to the PM.\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, interaction identified but abstract does not detail orthogonal methods (e.g., mutagenesis or reconstitution) for FAM102B specifically; functional consequence (vacuole accumulation) is attributed to BLTP2 loss, not FAM102B loss directly.\",\n      \"pmids\": [\"40899996\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FAM102B (EEIG2) acts as an adaptor protein that mediates binding of BLTP2 to the plasma membrane at ER-PM contact sites, contributing to ER tethering at tubular endosomes that become continuous with the PM and at macropinosomes fusing with the PM.\",\n      \"method\": \"Interaction mapping and localization studies in cell-based systems identifying FAM102B as a BLTP2 binding partner at membrane contact sites (preprint version of the peer-reviewed paper).\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, preprint; interaction identified but abstract lacks detail on orthogonal validation methods for FAM102B specifically; consistent with the peer-reviewed publication.\",\n      \"pmids\": [\"39974967\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"FAM102B (EEIG2) functions as an adaptor protein at ER-plasma membrane contact sites, where it interacts with the bridge-like lipid transfer protein BLTP2 to mediate ER tethering to the plasma membrane and support bulk lipid transport, thereby contributing to plasma membrane dynamics.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EEIG2 (FAM102B) functions as an adaptor protein at ER–plasma membrane contact sites, where it mediates recruitment of the bridge-like lipid transfer protein BLTP2 to the plasma membrane alongside phosphoinositides and N-BAR domain proteins [#0]. Through this interaction, EEIG2 contributes to ER tethering to the plasma membrane, supporting membrane contact at sites of bulk lipid transport [#0]. Beyond its role as a BLTP2 adaptor at these contact sites, no further mechanistic detail for EEIG2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether FAM102B/EEIG2 had a defined molecular role was unknown; identifying it as a BLTP2 binding partner at ER-PM contacts established it as an adaptor coupling a bridge-like lipid transfer protein to the plasma membrane.\",\n      \"evidence\": \"Interaction mapping and localization in cell-based systems, with loss-of-function showing PM-connected intracellular vacuole accumulation (peer-reviewed)\",\n      \"pmids\": [\"40899996\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No orthogonal validation (mutagenesis or reconstitution) for the FAM102B-BLTP2 interaction specifically\",\n        \"Vacuole accumulation phenotype attributed to BLTP2 loss, not directly to FAM102B loss\",\n        \"Mechanism by which FAM102B engages the PM (lipid vs protein determinants) not defined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The preprint extended the adaptor model by placing FAM102B-mediated BLTP2 tethering at tubular endosomes continuous with the PM and at macropinosomes fusing with the PM, broadening the membrane contexts where it operates.\",\n      \"evidence\": \"Interaction mapping and localization in cell-based systems (preprint)\",\n      \"pmids\": [\"39974967\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Preprint without detailed orthogonal validation for FAM102B\",\n        \"Direct demonstration of lipid transport dependence on FAM102B not shown\",\n        \"Stoichiometry and structural basis of the BLTP2 interaction unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How FAM102B selects and stabilizes specific contact-site geometries, and whether its adaptor function is required for bulk lipid transport itself, remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct loss-of-function phenotype attributed specifically to FAM102B\",\n        \"No structural or biochemical reconstitution of the FAM102B-BLTP2-PM assembly\",\n        \"Physiological consequences of FAM102B loss at the organism level uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"BLTP2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":2,"faith_pct":100.0}}