{"gene":"ERMAP","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2000,"finding":"ERMAP (erythroid membrane-associated protein) is a transmembrane protein with two extracellular immunoglobulin folds, a conserved B30.2 domain and phosphorylation consensus sequences in the cytoplasmic region. A GFP-ERMAP fusion protein localizes to the plasma membrane and cytoplasmic vesicles in transiently transfected 293T cells. Expression is restricted to fetal and adult erythroid tissues.","method":"cDNA cloning, sequence analysis, GFP fusion protein localization by fluorescence microscopy, Northern blot, in situ hybridization","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct subcellular localization via GFP fusion protein combined with sequence-based domain identification and tissue expression; single lab, multiple orthogonal methods","pmids":["10721728"],"is_preprint":false},{"year":2001,"finding":"Human ERMAP protein is predicted to contain one extracellular IgV fold (not two as in mouse), a cytoplasmic B30.2 domain, multiple kinase consensus sequences, and post-Golgi sorting signals. The protein localizes to the cell surface, particularly at sites of cell contact, and to cytoplasmic bodies, as demonstrated by an antibody specific for the IgV fold-derived peptide.","method":"Subtractive hybridization cloning, sequence analysis, immunofluorescence with peptide-specific antibody, in situ hybridization","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-surface localization confirmed by antibody-based detection; single lab, two orthogonal methods (antibody staining and sequence analysis)","pmids":["11549310"],"is_preprint":false},{"year":2001,"finding":"Human ERMAP protein (475 amino acids) shares high homology with butyrophilin and localizes to the plasma membrane and cytoplasmic bodies in erythroid cells. The extracellular IgV fold shares homology with butyrophilin family proteins, autoantigens, and avian blood group antigens. The cytoplasmic B30.2 domain is encoded by a single exon and is homologous with butyrophilin, pyrin, and MID1. The human ERMAP gene spans 19 kb on chromosome 1p34 and comprises 11 exons.","method":"cDNA and genomic sequencing, fluorescence microscopy, chromosomal mapping","journal":"Blood cells, molecules & diseases","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein localization and genomic structure established; single lab, multiple methods","pmids":["11783959"],"is_preprint":false},{"year":2002,"finding":"ERMAP encodes the Scianna blood group antigens including Rd. Sc2 antigen is caused by an ERMAP Gly57Arg substitution, the Rd antigen by an ERMAP Pro60Ala substitution, and the null Sc:-1,-2 phenotype by a 2-bp deletion in exon 3 causing a frameshift. PCR-SSP genotyping for these alleles was validated against serology.","method":"Gene sequencing of ERMAP in Scianna/Radin phenotype probands, PCR-SSP genotyping, serology validation","journal":"Blood","confidence":"High","confidence_rationale":"Tier 1 / Strong — mutation identification directly linked to blood group antigen expression, validated by both genotyping and serology; multiple alleles and phenotypes corroborated","pmids":["12393480"],"is_preprint":false},{"year":2016,"finding":"Full-length nucleotide sequences of ERMAP alleles encoding Scianna antigens were determined across 100 chromosomes from five population groups. Forty-eight distinct ERMAP alleles were resolved without ambiguity; 80 SNPs were identified, with 75 in noncoding sequences and 5 in coding regions. No SNP indicative of a nonfunctional allele was detected in the studied populations.","method":"Allele-specific PCR spanning 21.4 kb (exons 2–12 and introns), Sanger sequencing, population sampling","journal":"Transfusion","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic full-length allele sequencing across multiple populations; single study, robust allele resolution methodology","pmids":["27612015"],"is_preprint":false},{"year":2020,"finding":"ERMAP is a B7 family-related immunomodulatory protein expressed on the surface of antigen-presenting cells and some tumor tissues. ERMAP-Ig fusion protein inhibits CD4+ and CD8+ T cell functions in vitro. A putative ERMAP receptor is expressed on activated T cells and macrophages. Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro and inhibits tumor growth in mice. ERMAP-Ig administration ameliorates experimental autoimmune encephalomyelitis and type 1 diabetes in mouse models.","method":"ERMAP-Ig fusion protein in vitro T cell inhibition assays, antibody-mediated phagocytosis assay, in vivo mouse autoimmune disease models, tumor growth inhibition experiments","journal":"Cellular & molecular immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional readouts (T cell inhibition, phagocytosis, in vivo disease models); single lab with several orthogonal assays","pmids":["32620788"],"is_preprint":false},{"year":2023,"finding":"ERMAP expressed on cancer cell surfaces acts as a pro-phagocytic 'eat me' signal for Kupffer cells by interacting with galectin-9 on Kupffer cells in a glycosylation-dependent manner. Galectin-9 forms a bridging complex with ERMAP and the transmembrane receptor dectin-2 on Kupffer cells to induce detection and phagocytosis of cancer cells. In vivo CRISPR-Cas9 knockout screening identified ERMAP as required for Kupffer cell-mediated phagocytosis and control of liver metastasis.","method":"In vivo genome-wide CRISPR-Cas9 knockout screening, co-immunoprecipitation, glycosylation-dependent binding assays, Kupffer cell phagocytosis assays, liver metastasis mouse models","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 1 / Strong — CRISPR screen plus Co-IP binding partner identification plus mechanistic in vivo validation; multiple orthogonal methods in a single rigorous study","pmids":["37813965"],"is_preprint":false}],"current_model":"ERMAP is an erythroid and tumor cell-surface transmembrane glycoprotein carrying the Scianna blood group antigens (with Sc2 and Rd determined by specific missense mutations at residues 57 and 60, respectively); it contains an extracellular IgV fold homologous to the butyrophilin/B7 family and a cytoplasmic B30.2 domain, and functions as an immunomodulatory molecule that (1) inhibits T cell and macrophage activity through a receptor on activated immune cells, and (2) acts as a pro-phagocytic 'eat me' signal on cancer cells by forming a glycosylation-dependent bridging complex with galectin-9 and dectin-2 on Kupffer cells to promote phagocytosis and suppress liver metastasis."},"narrative":{"mechanistic_narrative":"ERMAP is an erythroid and immune-cell-surface transmembrane glycoprotein of the butyrophilin/B7 family that functions both as a blood group antigen carrier and as an immunomodulatory molecule [PMID:10721728, PMID:11783959, PMID:32620788]. The protein presents an extracellular immunoglobulin (IgV) fold homologous to butyrophilin, autoantigens, and avian blood group antigens, and a cytoplasmic B30.2 domain homologous to butyrophilin, pyrin, and MID1, with kinase consensus sequences and post-Golgi sorting signals in its cytoplasmic region [PMID:11549310, PMID:11783959]. It localizes to the plasma membrane—particularly at sites of cell contact—and to cytoplasmic vesicles/bodies [PMID:10721728, PMID:11549310]. ERMAP carries the Scianna blood group antigens: the Sc2 antigen arises from a Gly57Arg substitution and the Rd antigen from a Pro60Ala substitution, while a 2-bp frameshift deletion in exon 3 produces the null Sc:-1,-2 phenotype [PMID:12393480]. Functionally, ERMAP acts as a B7-related inhibitory ligand: as an Fc fusion it suppresses CD4+ and CD8+ T cell function through a receptor expressed on activated T cells and macrophages, and ERMAP-Ig ameliorates experimental autoimmune encephalomyelitis and type 1 diabetes in mice [PMID:32620788]. On cancer cells, ERMAP serves as a pro-phagocytic 'eat me' signal: it binds galectin-9 on Kupffer cells in a glycosylation-dependent manner, forming a bridging complex with the transmembrane receptor dectin-2 that drives Kupffer cell phagocytosis of cancer cells and suppresses liver metastasis [PMID:37813965].","teleology":[{"year":2000,"claim":"Established ERMAP as an erythroid-restricted transmembrane protein with a defined domain architecture and subcellular distribution, framing it as a candidate membrane receptor.","evidence":"cDNA cloning, sequence/domain analysis, GFP-fusion localization in 293T cells, Northern blot and in situ hybridization","pmids":["10721728"],"confidence":"Medium","gaps":["No binding partner or ligand identified","Function of the cytoplasmic B30.2 domain and phosphorylation sites untested","Mouse architecture (two Ig folds) not reconciled with later human single-IgV model"]},{"year":2001,"claim":"Refined the human ERMAP structure to a single extracellular IgV fold and confirmed cell-surface localization enriched at cell-cell contacts, hinting at an adhesion/signaling role.","evidence":"Subtractive hybridization cloning, sequence analysis, immunofluorescence with IgV peptide-specific antibody, in situ hybridization","pmids":["11549310","11783959"],"confidence":"Medium","gaps":["Functional consequence of localization at cell contacts not tested","No interacting partner at contact sites identified","Butyrophilin homology not functionally validated"]},{"year":2002,"claim":"Connected ERMAP genotype to phenotype by demonstrating it encodes the Scianna blood group antigens, mapping specific residues to antigenic determinants.","evidence":"Gene sequencing of Scianna/Radin probands, PCR-SSP genotyping, serology validation","pmids":["12393480"],"confidence":"High","gaps":["Does not address the molecular/physiological function of ERMAP beyond antigenicity","Phenotype of null individuals not mechanistically characterized"]},{"year":2016,"claim":"Catalogued ERMAP allelic diversity across populations, establishing the coding/noncoding variation landscape and confirming the rarity of nonfunctional alleles.","evidence":"Allele-specific PCR across exons 2–12, Sanger sequencing, multi-population sampling","pmids":["27612015"],"confidence":"Medium","gaps":["No functional consequence assigned to identified SNPs","Restricted to studied populations"]},{"year":2020,"claim":"Reframed ERMAP as a B7-family immunomodulator that inhibits T cells via a receptor on activated immune cells and whose blockade promotes anti-tumor phagocytosis.","evidence":"ERMAP-Ig in vitro T cell inhibition assays, antibody-mediated phagocytosis assays, mouse autoimmune (EAE, T1D) and tumor models","pmids":["32620788"],"confidence":"Medium","gaps":["The ERMAP receptor on activated T cells/macrophages was not molecularly identified","Mechanism linking inhibitory ligand activity to phagocytosis unresolved","Single-lab functional study"]},{"year":2023,"claim":"Defined the molecular basis of ERMAP's pro-phagocytic 'eat me' activity by identifying a glycosylation-dependent galectin-9/dectin-2 bridging complex controlling liver metastasis.","evidence":"In vivo genome-wide CRISPR-Cas9 screen, co-immunoprecipitation, glycosylation-dependent binding assays, Kupffer cell phagocytosis and liver metastasis mouse models","pmids":["37813965"],"confidence":"High","gaps":["Glycan structures mediating galectin-9 binding not fully defined","Relationship between this bridging complex and the T-cell-inhibitory receptor activity unclear","Role of the cytoplasmic B30.2 domain in signaling not addressed"]},{"year":null,"claim":"The identity of the inhibitory ERMAP receptor on activated T cells and the signaling function of its cytoplasmic B30.2 domain remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Cognate inhibitory receptor not molecularly identified","No structural model of ERMAP complexes","Function of cytoplasmic B30.2/phosphorylation sites uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0048018","term_label":"receptor ligand activity","supporting_discovery_ids":[5,6]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[5]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[5,6]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[3]}],"complexes":[],"partners":["LGALS9","CLEC6A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96PL5","full_name":"Erythroid membrane-associated protein","aliases":["Radin blood group antigen","Scianna blood group antigen"],"length_aa":475,"mass_kda":52.6,"function":"Possible role as a cell-adhesion or receptor molecule of erythroid cells","subcellular_location":"Cell membrane; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q96PL5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ERMAP","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/ERMAP","total_profiled":1310},"omim":[{"mim_id":"609017","title":"ERYTHROBLAST MEMBRANE-ASSOCIATED PROTEIN; ERMAP","url":"https://www.omim.org/entry/609017"},{"mim_id":"111750","title":"BLOOD GROUP--SCIANNA SYSTEM; SC","url":"https://www.omim.org/entry/111750"},{"mim_id":"111620","title":"RADIN BLOOD GROUP ANTIGEN; RD","url":"https://www.omim.org/entry/111620"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ERMAP"},"hgnc":{"alias_symbol":["BTN5"],"prev_symbol":["RD","SC"]},"alphafold":{"accession":"Q96PL5","domains":[{"cath_id":"2.60.40.10","chopping":"38-145","consensus_level":"high","plddt":86.3965,"start":38,"end":145},{"cath_id":"2.60.120.920","chopping":"235-413","consensus_level":"high","plddt":95.7322,"start":235,"end":413}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96PL5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96PL5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96PL5-F1-predicted_aligned_error_v6.png","plddt_mean":81.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ERMAP","jax_strain_url":"https://www.jax.org/strain/search?query=ERMAP"},"sequence":{"accession":"Q96PL5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96PL5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96PL5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96PL5"}},"corpus_meta":[{"pmid":"9771749","id":"PMC_9771749","title":"Eight 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A GFP-ERMAP fusion protein localizes to the plasma membrane and cytoplasmic vesicles in transiently transfected 293T cells. Expression is restricted to fetal and adult erythroid tissues.\",\n      \"method\": \"cDNA cloning, sequence analysis, GFP fusion protein localization by fluorescence microscopy, Northern blot, in situ hybridization\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct subcellular localization via GFP fusion protein combined with sequence-based domain identification and tissue expression; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"10721728\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Human ERMAP protein is predicted to contain one extracellular IgV fold (not two as in mouse), a cytoplasmic B30.2 domain, multiple kinase consensus sequences, and post-Golgi sorting signals. The protein localizes to the cell surface, particularly at sites of cell contact, and to cytoplasmic bodies, as demonstrated by an antibody specific for the IgV fold-derived peptide.\",\n      \"method\": \"Subtractive hybridization cloning, sequence analysis, immunofluorescence with peptide-specific antibody, in situ hybridization\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-surface localization confirmed by antibody-based detection; single lab, two orthogonal methods (antibody staining and sequence analysis)\",\n      \"pmids\": [\"11549310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Human ERMAP protein (475 amino acids) shares high homology with butyrophilin and localizes to the plasma membrane and cytoplasmic bodies in erythroid cells. The extracellular IgV fold shares homology with butyrophilin family proteins, autoantigens, and avian blood group antigens. The cytoplasmic B30.2 domain is encoded by a single exon and is homologous with butyrophilin, pyrin, and MID1. The human ERMAP gene spans 19 kb on chromosome 1p34 and comprises 11 exons.\",\n      \"method\": \"cDNA and genomic sequencing, fluorescence microscopy, chromosomal mapping\",\n      \"journal\": \"Blood cells, molecules & diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein localization and genomic structure established; single lab, multiple methods\",\n      \"pmids\": [\"11783959\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"ERMAP encodes the Scianna blood group antigens including Rd. Sc2 antigen is caused by an ERMAP Gly57Arg substitution, the Rd antigen by an ERMAP Pro60Ala substitution, and the null Sc:-1,-2 phenotype by a 2-bp deletion in exon 3 causing a frameshift. PCR-SSP genotyping for these alleles was validated against serology.\",\n      \"method\": \"Gene sequencing of ERMAP in Scianna/Radin phenotype probands, PCR-SSP genotyping, serology validation\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — mutation identification directly linked to blood group antigen expression, validated by both genotyping and serology; multiple alleles and phenotypes corroborated\",\n      \"pmids\": [\"12393480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Full-length nucleotide sequences of ERMAP alleles encoding Scianna antigens were determined across 100 chromosomes from five population groups. Forty-eight distinct ERMAP alleles were resolved without ambiguity; 80 SNPs were identified, with 75 in noncoding sequences and 5 in coding regions. No SNP indicative of a nonfunctional allele was detected in the studied populations.\",\n      \"method\": \"Allele-specific PCR spanning 21.4 kb (exons 2–12 and introns), Sanger sequencing, population sampling\",\n      \"journal\": \"Transfusion\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic full-length allele sequencing across multiple populations; single study, robust allele resolution methodology\",\n      \"pmids\": [\"27612015\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ERMAP is a B7 family-related immunomodulatory protein expressed on the surface of antigen-presenting cells and some tumor tissues. ERMAP-Ig fusion protein inhibits CD4+ and CD8+ T cell functions in vitro. A putative ERMAP receptor is expressed on activated T cells and macrophages. Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro and inhibits tumor growth in mice. ERMAP-Ig administration ameliorates experimental autoimmune encephalomyelitis and type 1 diabetes in mouse models.\",\n      \"method\": \"ERMAP-Ig fusion protein in vitro T cell inhibition assays, antibody-mediated phagocytosis assay, in vivo mouse autoimmune disease models, tumor growth inhibition experiments\",\n      \"journal\": \"Cellular & molecular immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional readouts (T cell inhibition, phagocytosis, in vivo disease models); single lab with several orthogonal assays\",\n      \"pmids\": [\"32620788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ERMAP expressed on cancer cell surfaces acts as a pro-phagocytic 'eat me' signal for Kupffer cells by interacting with galectin-9 on Kupffer cells in a glycosylation-dependent manner. Galectin-9 forms a bridging complex with ERMAP and the transmembrane receptor dectin-2 on Kupffer cells to induce detection and phagocytosis of cancer cells. In vivo CRISPR-Cas9 knockout screening identified ERMAP as required for Kupffer cell-mediated phagocytosis and control of liver metastasis.\",\n      \"method\": \"In vivo genome-wide CRISPR-Cas9 knockout screening, co-immunoprecipitation, glycosylation-dependent binding assays, Kupffer cell phagocytosis assays, liver metastasis mouse models\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — CRISPR screen plus Co-IP binding partner identification plus mechanistic in vivo validation; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"37813965\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ERMAP is an erythroid and tumor cell-surface transmembrane glycoprotein carrying the Scianna blood group antigens (with Sc2 and Rd determined by specific missense mutations at residues 57 and 60, respectively); it contains an extracellular IgV fold homologous to the butyrophilin/B7 family and a cytoplasmic B30.2 domain, and functions as an immunomodulatory molecule that (1) inhibits T cell and macrophage activity through a receptor on activated immune cells, and (2) acts as a pro-phagocytic 'eat me' signal on cancer cells by forming a glycosylation-dependent bridging complex with galectin-9 and dectin-2 on Kupffer cells to promote phagocytosis and suppress liver metastasis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ERMAP is an erythroid and immune-cell-surface transmembrane glycoprotein of the butyrophilin/B7 family that functions both as a blood group antigen carrier and as an immunomodulatory molecule [#0, #2, #5]. The protein presents an extracellular immunoglobulin (IgV) fold homologous to butyrophilin, autoantigens, and avian blood group antigens, and a cytoplasmic B30.2 domain homologous to butyrophilin, pyrin, and MID1, with kinase consensus sequences and post-Golgi sorting signals in its cytoplasmic region [#1, #2]. It localizes to the plasma membrane—particularly at sites of cell contact—and to cytoplasmic vesicles/bodies [#0, #1]. ERMAP carries the Scianna blood group antigens: the Sc2 antigen arises from a Gly57Arg substitution and the Rd antigen from a Pro60Ala substitution, while a 2-bp frameshift deletion in exon 3 produces the null Sc:-1,-2 phenotype [#3]. Functionally, ERMAP acts as a B7-related inhibitory ligand: as an Fc fusion it suppresses CD4+ and CD8+ T cell function through a receptor expressed on activated T cells and macrophages, and ERMAP-Ig ameliorates experimental autoimmune encephalomyelitis and type 1 diabetes in mice [#5]. On cancer cells, ERMAP serves as a pro-phagocytic 'eat me' signal: it binds galectin-9 on Kupffer cells in a glycosylation-dependent manner, forming a bridging complex with the transmembrane receptor dectin-2 that drives Kupffer cell phagocytosis of cancer cells and suppresses liver metastasis [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Established ERMAP as an erythroid-restricted transmembrane protein with a defined domain architecture and subcellular distribution, framing it as a candidate membrane receptor.\",\n      \"evidence\": \"cDNA cloning, sequence/domain analysis, GFP-fusion localization in 293T cells, Northern blot and in situ hybridization\",\n      \"pmids\": [\"10721728\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No binding partner or ligand identified\", \"Function of the cytoplasmic B30.2 domain and phosphorylation sites untested\", \"Mouse architecture (two Ig folds) not reconciled with later human single-IgV model\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Refined the human ERMAP structure to a single extracellular IgV fold and confirmed cell-surface localization enriched at cell-cell contacts, hinting at an adhesion/signaling role.\",\n      \"evidence\": \"Subtractive hybridization cloning, sequence analysis, immunofluorescence with IgV peptide-specific antibody, in situ hybridization\",\n      \"pmids\": [\"11549310\", \"11783959\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of localization at cell contacts not tested\", \"No interacting partner at contact sites identified\", \"Butyrophilin homology not functionally validated\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Connected ERMAP genotype to phenotype by demonstrating it encodes the Scianna blood group antigens, mapping specific residues to antigenic determinants.\",\n      \"evidence\": \"Gene sequencing of Scianna/Radin probands, PCR-SSP genotyping, serology validation\",\n      \"pmids\": [\"12393480\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address the molecular/physiological function of ERMAP beyond antigenicity\", \"Phenotype of null individuals not mechanistically characterized\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Catalogued ERMAP allelic diversity across populations, establishing the coding/noncoding variation landscape and confirming the rarity of nonfunctional alleles.\",\n      \"evidence\": \"Allele-specific PCR across exons 2–12, Sanger sequencing, multi-population sampling\",\n      \"pmids\": [\"27612015\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional consequence assigned to identified SNPs\", \"Restricted to studied populations\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Reframed ERMAP as a B7-family immunomodulator that inhibits T cells via a receptor on activated immune cells and whose blockade promotes anti-tumor phagocytosis.\",\n      \"evidence\": \"ERMAP-Ig in vitro T cell inhibition assays, antibody-mediated phagocytosis assays, mouse autoimmune (EAE, T1D) and tumor models\",\n      \"pmids\": [\"32620788\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The ERMAP receptor on activated T cells/macrophages was not molecularly identified\", \"Mechanism linking inhibitory ligand activity to phagocytosis unresolved\", \"Single-lab functional study\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined the molecular basis of ERMAP's pro-phagocytic 'eat me' activity by identifying a glycosylation-dependent galectin-9/dectin-2 bridging complex controlling liver metastasis.\",\n      \"evidence\": \"In vivo genome-wide CRISPR-Cas9 screen, co-immunoprecipitation, glycosylation-dependent binding assays, Kupffer cell phagocytosis and liver metastasis mouse models\",\n      \"pmids\": [\"37813965\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Glycan structures mediating galectin-9 binding not fully defined\", \"Relationship between this bridging complex and the T-cell-inhibitory receptor activity unclear\", \"Role of the cytoplasmic B30.2 domain in signaling not addressed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The identity of the inhibitory ERMAP receptor on activated T cells and the signaling function of its cytoplasmic B30.2 domain remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cognate inhibitory receptor not molecularly identified\", \"No structural model of ERMAP complexes\", \"Function of cytoplasmic B30.2/phosphorylation sites uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"LGALS9\", \"CLEC6A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}