{"gene":"MLEC","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2025,"finding":"Malectin (MLEC) promotes coronavirus replication by supporting viral protein biogenesis through its glycoprotein quality control activity. Knockdown of MLEC significantly reduces infectious titers of murine hepatitis virus (a model betacoronavirus). During infection, viral nsp2 interacts with MLEC-associated proteins, and the MLEC interactome is drastically altered but retains association with the Oligosaccharyltransferase (OST) complex. MLEC promotes viral glycoprotein production and genome replication through its quality control function, and also promotes SARS-CoV-2 replication.","method":"Quantitative proteomics, functional genetic screening (siRNA knockdown), infectious titer assays, co-immunoprecipitation/interactome analysis","journal":"bioRxiv (preprint)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interactome mapping, siRNA knockdown with defined phenotypic readout (infectious titer), multiple orthogonal methods in single preprint lab study; not yet peer-reviewed","pmids":["38895409"],"is_preprint":true},{"year":2018,"finding":"MLEC gene polymorphisms (rs10431386 and rs7964786, C alleles) reduce MLEC expression in blood cells and macrophage cell lines. In vitro experiments demonstrated that MLEC promotes M1-to-M2 macrophage polarization; reduced MLEC expression inhibits this polarization, linking MLEC to immune regulation.","method":"SNP genotyping, in vitro macrophage polarization assays, gene expression analysis in macrophage cell line","journal":"Clinical genetics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single in vitro functional assay for macrophage polarization with limited mechanistic detail in abstract","pmids":["28972276"],"is_preprint":false}],"current_model":"Malectin (MLEC) is an endoplasmic reticulum glycoprotein quality control factor that associates with the Oligosaccharyltransferase (OST) complex and promotes viral glycoprotein biogenesis and genome replication during coronavirus infection; it also appears to influence macrophage M1-to-M2 polarization, though the mechanistic basis of the latter remains poorly characterized."},"narrative":{"mechanistic_narrative":"Malectin (MLEC) is an endoplasmic reticulum glycoprotein quality control factor that supports the biogenesis of nascent glycoproteins through its association with the Oligosaccharyltransferase (OST) complex [PMID:38895409]. During coronavirus infection it is co-opted to promote viral glycoprotein production and genome replication: knockdown of MLEC reduces infectious titers of murine hepatitis virus and impairs SARS-CoV-2 replication, while viral nsp2 engages MLEC-associated proteins and the MLEC interactome is remodeled yet retains its OST association [PMID:38895409]. Beyond this quality-control role, MLEC has been linked to immune regulation, where it promotes M1-to-M2 macrophage polarization [PMID:28972276]. The molecular basis of the macrophage polarization activity has not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Established a candidate immune-regulatory role for MLEC by tying expression-lowering polymorphisms to a defined cellular phenotype, raising the question of how an ER quality-control factor influences immune cell behavior.","evidence":"SNP genotyping with in vitro macrophage polarization and expression assays in macrophage cell lines","pmids":["28972276"],"confidence":"Low","gaps":["Single in vitro functional assay with limited mechanistic detail; not independently confirmed","No molecular pathway linking MLEC to polarization defined","No connection to its ER glycoprotein quality-control function established"]},{"year":2025,"claim":"Defined MLEC's molecular activity as ER glycoprotein quality control acting through the OST complex and showed this function is exploited during coronavirus infection to support viral glycoprotein biogenesis and replication.","evidence":"Quantitative proteomics, siRNA knockdown with infectious-titer readout, and interactome/co-IP analysis in coronavirus-infected cells (preprint)","pmids":["38895409"],"confidence":"Medium","gaps":["Not yet peer-reviewed","Specific glycoprotein substrates handled by MLEC during infection not identified","Mechanism by which nsp2 reshapes the MLEC interactome unresolved"]},{"year":null,"claim":"How MLEC's ER glycoprotein quality-control activity mechanistically connects to its reported role in macrophage polarization remains unknown.","evidence":"No discovery bridges the two functional contexts","pmids":[],"confidence":"Low","gaps":["No unifying mechanism linking glycoprotein handling to immune cell phenotype","Substrate repertoire of MLEC in either context undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0]}],"complexes":[],"partners":["OST"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q14165","full_name":"Malectin","aliases":[],"length_aa":292,"mass_kda":32.2,"function":"Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation (By similarity)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/Q14165/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MLEC","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DAD1","stoichiometry":10.0},{"gene":"DDOST","stoichiometry":10.0},{"gene":"OSTC","stoichiometry":10.0},{"gene":"RPN1","stoichiometry":10.0},{"gene":"RPN2","stoichiometry":10.0},{"gene":"STT3A","stoichiometry":10.0},{"gene":"STT3B","stoichiometry":10.0},{"gene":"KRTCAP2","stoichiometry":4.0},{"gene":"CANX","stoichiometry":0.2},{"gene":"CEP78","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MLEC","total_profiled":1310},"omim":[{"mim_id":"613802","title":"MALECTIN; MLEC","url":"https://www.omim.org/entry/613802"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MLEC"},"hgnc":{"alias_symbol":[],"prev_symbol":["KIAA0152"]},"alphafold":{"accession":"Q14165","domains":[{"cath_id":"2.60.120.430","chopping":"43-215","consensus_level":"high","plddt":97.1465,"start":43,"end":215}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14165","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14165-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14165-F1-predicted_aligned_error_v6.png","plddt_mean":80.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MLEC","jax_strain_url":"https://www.jax.org/strain/search?query=MLEC"},"sequence":{"accession":"Q14165","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14165.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14165/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14165"}},"corpus_meta":[{"pmid":"8179182","id":"PMC_8179182","title":"An assay for transforming growth 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chaperones","url":"https://pubmed.ncbi.nlm.nih.gov/39938773","citation_count":4,"is_preprint":false},{"pmid":"35883582","id":"PMC_35883582","title":"Hypertensive Stimuli Indirectly Stimulate Lymphangiogenesis through Immune Cell Secreted Factors.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35883582","citation_count":3,"is_preprint":false},{"pmid":"39386830","id":"PMC_39386830","title":"Targeted metabolomics of muscle amino acid profles and hepatic transcriptomics analyses in grass carp (Ctenopharyngodon idellus) fed with broad beans.","date":"2024","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/39386830","citation_count":3,"is_preprint":false},{"pmid":"41323652","id":"PMC_41323652","title":"Integrated analysis of N-glycosylation and Alzheimer's disease: identifying key biomarkers and mechanisms.","date":"2025","source":"Frontiers in aging neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/41323652","citation_count":1,"is_preprint":false},{"pmid":"34626412","id":"PMC_34626412","title":"Application of a Mutant Cell Library to Determine the Structure-Function Relationship of Heparan Sulfate in Facilitating FGF2-FGFR1 Signaling.","date":"2022","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/34626412","citation_count":1,"is_preprint":false},{"pmid":"20478381","id":"PMC_20478381","title":"Kynurenine inhibits fibroblast growth factor 2-mediated expression of crystallins and MIP26 in lens epithelial cells.","date":"2010","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/20478381","citation_count":1,"is_preprint":false},{"pmid":"24513006","id":"PMC_24513006","title":"[Establishment of mouse lens epithelial cell lines with the genotype of Hsf4-/-].","date":"2013","source":"[Zhonghua yan ke za zhi] Chinese journal of ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/24513006","citation_count":1,"is_preprint":false},{"pmid":"41042795","id":"PMC_41042795","title":"A multi-layer encoder prediction model for individual sample specific gene combination effect (MLEC-iGeneCombo).","date":"2025","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/41042795","citation_count":0,"is_preprint":false},{"pmid":"41016239","id":"PMC_41016239","title":"Glypican 1 mechanosensing mediates eNOS uncoupling during hydrostatic pulmonary edema.","date":"2025","source":"Redox biology","url":"https://pubmed.ncbi.nlm.nih.gov/41016239","citation_count":0,"is_preprint":false},{"pmid":"38895409","id":"PMC_38895409","title":"The glycoprotein quality control factor Malectin promotes coronavirus replication and viral protein biogenesis.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38895409","citation_count":0,"is_preprint":false},{"pmid":"38645867","id":"PMC_38645867","title":"[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning].","date":"2024","source":"Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition","url":"https://pubmed.ncbi.nlm.nih.gov/38645867","citation_count":0,"is_preprint":false},{"pmid":"42187511","id":"PMC_42187511","title":"The Role of NAT10-Mediated ac4C Modification in Osteoblast Function and Bone Formation: Insights from Integrative Bioinformatics and Experimental Validation.","date":"2026","source":"Physiological research","url":"https://pubmed.ncbi.nlm.nih.gov/42187511","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.11.26.690852","title":"Discovery of miRNA–RNA Biomarkers for Risk Stratification in Acute Myeloid Leukemia with Multi-Cohort Validation","date":"2025-12-01","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.26.690852","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":46314,"output_tokens":999,"usd":0.076964,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7014,"output_tokens":1194,"usd":0.03246,"stage2_stop_reason":"end_turn"},"total_usd":0.109424,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical MLEC protein (Malectin, KIAA0152) — an endoplasmic reticulum glycoprotein quality control factor — versus papers where \"MLEC\" is an acronym for \"mink lung epithelial cells,\" \"mouse lung endothelial cells,\" \"mouse lens epithelial cells,\" or other abbreviations.\n\nThe canonical MLEC/Malectin protein papers are:\n- Paper [76]: Direct mechanistic study of Malectin (MLEC) in coronavirus replication\n- Paper [65]: MLEC gene polymorphisms and macrophage polarization (mentions in vitro experiments)\n- Paper [39]: Proteomic identification of MLEC in thyroid carcinoma (expression study, not mechanistic)\n- Paper [20]: KIAA0152 mentioned in heart failure bioinformatics (no mechanism)\n- Paper [67]: MLEC listed as chaperone upregulated in atopic dermatitis (expression)\n- Paper [69]: MLEC as hub gene in grass carp liver transcriptomics (not mammalian mechanism)\n- Paper [70]: MLEC as N-glycosylation biomarker in AD (bioinformatics)\n\nPapers [1]-[19], [21]-[38], [40]-[48], [50]-[64], [66], [68], [71]-[75], [77]-[79] use MLEC as an abbreviation for other cell types, not the Malectin protein.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"Malectin (MLEC) promotes coronavirus replication by supporting viral protein biogenesis through its glycoprotein quality control activity. Knockdown of MLEC significantly reduces infectious titers of murine hepatitis virus (a model betacoronavirus). During infection, viral nsp2 interacts with MLEC-associated proteins, and the MLEC interactome is drastically altered but retains association with the Oligosaccharyltransferase (OST) complex. MLEC promotes viral glycoprotein production and genome replication through its quality control function, and also promotes SARS-CoV-2 replication.\",\n      \"method\": \"Quantitative proteomics, functional genetic screening (siRNA knockdown), infectious titer assays, co-immunoprecipitation/interactome analysis\",\n      \"journal\": \"bioRxiv (preprint)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interactome mapping, siRNA knockdown with defined phenotypic readout (infectious titer), multiple orthogonal methods in single preprint lab study; not yet peer-reviewed\",\n      \"pmids\": [\"38895409\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MLEC gene polymorphisms (rs10431386 and rs7964786, C alleles) reduce MLEC expression in blood cells and macrophage cell lines. In vitro experiments demonstrated that MLEC promotes M1-to-M2 macrophage polarization; reduced MLEC expression inhibits this polarization, linking MLEC to immune regulation.\",\n      \"method\": \"SNP genotyping, in vitro macrophage polarization assays, gene expression analysis in macrophage cell line\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single in vitro functional assay for macrophage polarization with limited mechanistic detail in abstract\",\n      \"pmids\": [\"28972276\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Malectin (MLEC) is an endoplasmic reticulum glycoprotein quality control factor that associates with the Oligosaccharyltransferase (OST) complex and promotes viral glycoprotein biogenesis and genome replication during coronavirus infection; it also appears to influence macrophage M1-to-M2 polarization, though the mechanistic basis of the latter remains poorly characterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Malectin (MLEC) is an endoplasmic reticulum glycoprotein quality control factor that supports the biogenesis of nascent glycoproteins through its association with the Oligosaccharyltransferase (OST) complex [#0]. During coronavirus infection it is co-opted to promote viral glycoprotein production and genome replication: knockdown of MLEC reduces infectious titers of murine hepatitis virus and impairs SARS-CoV-2 replication, while viral nsp2 engages MLEC-associated proteins and the MLEC interactome is remodeled yet retains its OST association [#0]. Beyond this quality-control role, MLEC has been linked to immune regulation, where it promotes M1-to-M2 macrophage polarization [#1]. The molecular basis of the macrophage polarization activity has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Established a candidate immune-regulatory role for MLEC by tying expression-lowering polymorphisms to a defined cellular phenotype, raising the question of how an ER quality-control factor influences immune cell behavior.\",\n      \"evidence\": \"SNP genotyping with in vitro macrophage polarization and expression assays in macrophage cell lines\",\n      \"pmids\": [\"28972276\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single in vitro functional assay with limited mechanistic detail; not independently confirmed\",\n        \"No molecular pathway linking MLEC to polarization defined\",\n        \"No connection to its ER glycoprotein quality-control function established\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defined MLEC's molecular activity as ER glycoprotein quality control acting through the OST complex and showed this function is exploited during coronavirus infection to support viral glycoprotein biogenesis and replication.\",\n      \"evidence\": \"Quantitative proteomics, siRNA knockdown with infectious-titer readout, and interactome/co-IP analysis in coronavirus-infected cells (preprint)\",\n      \"pmids\": [\"38895409\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Not yet peer-reviewed\",\n        \"Specific glycoprotein substrates handled by MLEC during infection not identified\",\n        \"Mechanism by which nsp2 reshapes the MLEC interactome unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MLEC's ER glycoprotein quality-control activity mechanistically connects to its reported role in macrophage polarization remains unknown.\",\n      \"evidence\": \"No discovery bridges the two functional contexts\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unifying mechanism linking glycoprotein handling to immune cell phenotype\",\n        \"Substrate repertoire of MLEC in either context undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"OST\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}