{"gene":"DPM2","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":1998,"finding":"DPM2 is an 84 amino acid membrane protein localized to the endoplasmic reticulum that forms a complex with DPM1, is essential for correct ER localization and stable expression of DPM1, and enhances DPM1's binding of dolichol phosphate (a substrate of DPM synthase). DPM1 is catalytic (a DPM1 fusion protein stably expressed in the ER synthesized DPM without DPM2), while DPM2 plays a regulatory role.","method":"Expression cloning in Lec15 (DPM2-null) CHO cells; subcellular fractionation/ER localization; co-immunoprecipitation of DPM1-DPM2 complex; in vitro DPM synthase assay; dolichol phosphate binding assay; rescue by DPM1 fusion protein","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (expression cloning, Co-IP, localization, binding assay, enzymatic assay) in a single rigorous study, foundational paper replicated by subsequent work","pmids":["9724629"],"is_preprint":false},{"year":2000,"finding":"Human DPM synthase is a three-subunit complex: catalytic DPM1, regulatory DPM2, and DPM3. DPM3 associates with DPM1 via its C-terminal domain and with DPM2 via its N-terminal portion. DPM2 stabilizes DPM3, and DPM3 stabilizes DPM1. DPM2 also contributes to enzymatic activity (10-fold higher DPM synthase activity in the presence of DPM2). Overexpression of DPM3 in Lec15 (DPM2-null) cells restored DPM biosynthesis by directly stabilizing DPM1.","method":"Co-immunoprecipitation of subunit interactions; complementation assay in Lec15 cells; DPM synthase activity assay; domain mapping of DPM3 interactions","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, enzymatic activity assay, genetic complementation, multiple orthogonal methods, replicated across labs","pmids":["10835346"],"is_preprint":false},{"year":2000,"finding":"DPM2 associates with GPI-N-acetylglucosaminyltransferase (GPI-GnT) through interactions with subunits PIG-A, PIG-C, and GPI1, and enhances GPI-GnT activity 3-fold. However, DPM2 is not essential for GPI-GnT, as Lec15 (DPM2-null) cells still synthesize early GPI intermediates. DPM2 thus co-regulates both DPM synthase and GPI-GnT.","method":"Co-immunoprecipitation of DPM2 with GPI-GnT subunits; GPI-GnT enzymatic activity assay in Lec15 vs. wild-type cells; analysis of GPI biosynthesis intermediates","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP of multiple subunit interactions, enzymatic activity assay, null-mutant analysis with biochemical readout, single rigorous study with multiple orthogonal methods","pmids":["10944123"],"is_preprint":false},{"year":2003,"finding":"A single point mutation G29A in the DPM2 coding region (resulting in Gly10Glu amino acid change) in Lec15.1 CHO cells causes drastically reduced DPM2 protein expression and poorly corrects the Lec15.1 phenotype (DPM synthase deficiency), whereas wild-type DPM2 restores activity. DPM1 sequence is identical in wild-type and Lec15.1 cells and DPM1 transfection does not rescue the phenotype.","method":"Sequencing of DPM2 gene; transfection/complementation assay; western blot of DPM2 protein levels; DPM synthase activity assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complementation assay with protein quantification and activity measurement, single lab, two orthogonal methods","pmids":["14680801"],"is_preprint":false}],"current_model":"DPM2 is an 84-amino acid ER-resident membrane protein that forms an obligate regulatory subunit of the trimeric human DPM (dolichol-phosphate-mannose) synthase complex (DPM1–DPM2–DPM3): it stabilizes DPM3, which in turn stabilizes the catalytic subunit DPM1 in the ER, enhances DPM1's dolichol phosphate binding, and boosts DPM synthase enzymatic activity ~10-fold; additionally, DPM2 associates with GPI-N-acetylglucosaminyltransferase (via PIG-A, PIG-C, and GPI1) and enhances its activity ~3-fold, thereby co-regulating two key glycosylation pathways."},"narrative":{"mechanistic_narrative":"DPM2 is an ER-resident membrane protein that functions as an obligate regulatory subunit of the human dolichol-phosphate-mannose (DPM) synthase complex, coordinating two distinct glycosylation pathways [PMID:9724629, PMID:10944123]. Within the trimeric DPM synthase, DPM2 stabilizes DPM3, which in turn stabilizes the catalytic subunit DPM1 in the ER; DPM3 bridges the complex by binding DPM1 through its C-terminal domain and DPM2 through its N-terminal portion [PMID:10835346]. DPM2 is required for correct ER localization and stable expression of DPM1 and enhances DPM1's binding of its dolichol phosphate substrate, raising overall DPM synthase activity roughly 10-fold, while DPM1 itself carries the catalytic function [PMID:9724629, PMID:10835346]. Beyond DPM synthase, DPM2 associates with GPI-N-acetylglucosaminyltransferase via the PIG-A, PIG-C, and GPI1 subunits and enhances its activity ~3-fold, though it is dispensable for early GPI intermediate synthesis, marking DPM2 as a shared co-regulator of DPM synthesis and GPI anchor biosynthesis [PMID:10944123]. A G29A point mutation producing a Gly10Glu substitution sharply reduces DPM2 protein levels and fails to restore DPM synthase activity, demonstrating that DPM2 abundance is rate-limiting for complex function [PMID:14680801].","teleology":[{"year":1998,"claim":"Established that DPM synthase is not a single enzyme but requires a second ER protein, defining DPM2 as a regulatory partner that controls the localization, stability, and substrate binding of the catalytic DPM1.","evidence":"Expression cloning in DPM2-null Lec15 CHO cells with Co-IP, ER fractionation, dolichol phosphate binding and DPM synthase assays, plus rescue by an ER-anchored DPM1 fusion protein","pmids":["9724629"],"confidence":"High","gaps":["Did not resolve the full subunit composition of the complex","Mechanism by which DPM2 enhances dolichol phosphate binding not structurally defined"]},{"year":2000,"claim":"Resolved the DPM synthase as a three-subunit complex and ordered the stabilization hierarchy, showing DPM2 acts upstream of DPM3, which directly stabilizes catalytic DPM1.","evidence":"Reciprocal Co-IP and domain mapping of DPM3 interactions, genetic complementation in Lec15 cells, and DPM synthase activity assays","pmids":["10835346"],"confidence":"High","gaps":["No structural model of the DPM1-DPM2-DPM3 assembly","Stoichiometry of the trimeric complex not determined"]},{"year":2000,"claim":"Extended DPM2's role beyond mannose donor synthesis by showing it physically associates with and enhances GPI-N-acetylglucosaminyltransferase, positioning DPM2 as a shared regulator across two glycosylation pathways.","evidence":"Co-IP of DPM2 with PIG-A, PIG-C and GPI1, GPI-GnT activity assays in Lec15 versus wild-type cells, and analysis of GPI biosynthesis intermediates","pmids":["10944123"],"confidence":"High","gaps":["DPM2 is non-essential for GPI-GnT, so its precise contribution to GPI anchor output is unclear","Whether DPM2 simultaneously engages both complexes or partitions between them is unknown"]},{"year":2003,"claim":"Demonstrated that DPM2 protein abundance is rate-limiting by linking a coding point mutation to loss of DPM2 expression and failure to restore DPM synthase activity.","evidence":"Sequencing of the DPM2 gene in Lec15.1 cells, complementation transfection, western blot quantification, and DPM synthase activity assay","pmids":["14680801"],"confidence":"Medium","gaps":["Single lab with two orthogonal methods","Whether the Gly10Glu change disrupts folding, membrane insertion, or partner binding was not dissected"]},{"year":null,"claim":"The structural basis of how DPM2 stabilizes its partners and enhances substrate binding, and its potential role in human congenital disorders of glycosylation, remains unaddressed in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of the DPM synthase complex","No human disease mutation directly characterized in the timeline","Regulation of DPM2 expression and turnover not studied"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1,2]}],"complexes":["DPM synthase (DPM1-DPM2-DPM3)","GPI-N-acetylglucosaminyltransferase"],"partners":["DPM1","DPM3","PIGA","PIGC","GPI1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O94777","full_name":"Dolichol phosphate-mannose biosynthesis regulatory protein","aliases":["Dolichol-phosphate mannose synthase subunit 2","DPM synthase subunit 2"],"length_aa":84,"mass_kda":9.3,"function":"Regulates the biosynthesis of dolichol phosphate-mannose (PubMed:10835346). Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization and stable expression of DPM1 (PubMed:10835346). Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis (PubMed:16162815). May act by regulating the GPI-GNT complex (PubMed:10944123)","subcellular_location":"Endoplasmic reticulum membrane","url":"https://www.uniprot.org/uniprotkb/O94777/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DPM2","classification":"Common Essential","n_dependent_lines":421,"n_total_lines":1208,"dependency_fraction":0.3485099337748344},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DPM2","total_profiled":1310},"omim":[{"mim_id":"615042","title":"CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Iu; CDG1U","url":"https://www.omim.org/entry/615042"},{"mim_id":"609837","title":"SMALL NUCLEOLAR RNA, C/D BOX, 115-1; SNORD115-1","url":"https://www.omim.org/entry/609837"},{"mim_id":"605951","title":"DOLICHYL-PHOSPHATE MANNOSYLTRANSFERASE 3; DPM3","url":"https://www.omim.org/entry/605951"},{"mim_id":"604041","title":"MANNOSE-P-DOLICHOL UTILIZATION DEFECT 1; MPDU1","url":"https://www.omim.org/entry/604041"},{"mim_id":"603564","title":"DOLICHYL-PHOSPHATE MANNOSYLTRANSFERASE 2, REGULATORY SUBUNIT; DPM2","url":"https://www.omim.org/entry/603564"}],"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/DPM2"},"hgnc":{"alias_symbol":["MGC21559","MGC111193"],"prev_symbol":[]},"alphafold":{"accession":"O94777","domains":[{"cath_id":"-","chopping":"2-45","consensus_level":"medium","plddt":94.0348,"start":2,"end":45},{"cath_id":"1.20.5","chopping":"47-84","consensus_level":"medium","plddt":89.8937,"start":47,"end":84}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O94777","model_url":"https://alphafold.ebi.ac.uk/files/AF-O94777-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O94777-F1-predicted_aligned_error_v6.png","plddt_mean":92.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DPM2","jax_strain_url":"https://www.jax.org/strain/search?query=DPM2"},"sequence":{"accession":"O94777","fasta_url":"https://rest.uniprot.org/uniprotkb/O94777.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O94777/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O94777"}},"corpus_meta":[{"pmid":"10835346","id":"PMC_10835346","title":"Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.","date":"2000","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/10835346","citation_count":117,"is_preprint":false},{"pmid":"23109149","id":"PMC_23109149","title":"DPM2-CDG: a muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy.","date":"2012","source":"Annals of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/23109149","citation_count":112,"is_preprint":false},{"pmid":"10944123","id":"PMC_10944123","title":"Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2.","date":"2000","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/10944123","citation_count":110,"is_preprint":false},{"pmid":"9724629","id":"PMC_9724629","title":"DPM2 regulates biosynthesis of dolichol phosphate-mannose in mammalian cells: correct subcellular localization and stabilization of DPM1, and binding of dolichol phosphate.","date":"1998","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/9724629","citation_count":96,"is_preprint":false},{"pmid":"33129689","id":"PMC_33129689","title":"Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation.","date":"2020","source":"Molecular genetics and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/33129689","citation_count":20,"is_preprint":false},{"pmid":"14680801","id":"PMC_14680801","title":"A single point mutation resulting in an adversely reduced expression of DPM2 in the Lec15.1 cells.","date":"2003","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/14680801","citation_count":7,"is_preprint":false},{"pmid":"21521073","id":"PMC_21521073","title":"Cloning and functional analysis of the dpm2 and dpm3 genes from Trichoderma reesei expressed in a Saccharomyces cerevisiae dpm1Δ mutant strain.","date":"2011","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21521073","citation_count":5,"is_preprint":false},{"pmid":"37152991","id":"PMC_37152991","title":"Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment.","date":"2023","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37152991","citation_count":3,"is_preprint":false},{"pmid":"14680839","id":"PMC_14680839","title":"The divergent 5' ends of DPM2 mRNAs originate from the alternative splicing of two adjacent introns: characterization of the hamster DPM2 gene.","date":"2003","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/14680839","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6345,"output_tokens":1456,"usd":0.020438,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8038,"output_tokens":1999,"usd":0.045082,"stage2_stop_reason":"end_turn"},"total_usd":0.06552,"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\": 1998,\n      \"finding\": \"DPM2 is an 84 amino acid membrane protein localized to the endoplasmic reticulum that forms a complex with DPM1, is essential for correct ER localization and stable expression of DPM1, and enhances DPM1's binding of dolichol phosphate (a substrate of DPM synthase). DPM1 is catalytic (a DPM1 fusion protein stably expressed in the ER synthesized DPM without DPM2), while DPM2 plays a regulatory role.\",\n      \"method\": \"Expression cloning in Lec15 (DPM2-null) CHO cells; subcellular fractionation/ER localization; co-immunoprecipitation of DPM1-DPM2 complex; in vitro DPM synthase assay; dolichol phosphate binding assay; rescue by DPM1 fusion protein\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (expression cloning, Co-IP, localization, binding assay, enzymatic assay) in a single rigorous study, foundational paper replicated by subsequent work\",\n      \"pmids\": [\"9724629\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Human DPM synthase is a three-subunit complex: catalytic DPM1, regulatory DPM2, and DPM3. DPM3 associates with DPM1 via its C-terminal domain and with DPM2 via its N-terminal portion. DPM2 stabilizes DPM3, and DPM3 stabilizes DPM1. DPM2 also contributes to enzymatic activity (10-fold higher DPM synthase activity in the presence of DPM2). Overexpression of DPM3 in Lec15 (DPM2-null) cells restored DPM biosynthesis by directly stabilizing DPM1.\",\n      \"method\": \"Co-immunoprecipitation of subunit interactions; complementation assay in Lec15 cells; DPM synthase activity assay; domain mapping of DPM3 interactions\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, enzymatic activity assay, genetic complementation, multiple orthogonal methods, replicated across labs\",\n      \"pmids\": [\"10835346\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"DPM2 associates with GPI-N-acetylglucosaminyltransferase (GPI-GnT) through interactions with subunits PIG-A, PIG-C, and GPI1, and enhances GPI-GnT activity 3-fold. However, DPM2 is not essential for GPI-GnT, as Lec15 (DPM2-null) cells still synthesize early GPI intermediates. DPM2 thus co-regulates both DPM synthase and GPI-GnT.\",\n      \"method\": \"Co-immunoprecipitation of DPM2 with GPI-GnT subunits; GPI-GnT enzymatic activity assay in Lec15 vs. wild-type cells; analysis of GPI biosynthesis intermediates\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP of multiple subunit interactions, enzymatic activity assay, null-mutant analysis with biochemical readout, single rigorous study with multiple orthogonal methods\",\n      \"pmids\": [\"10944123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"A single point mutation G29A in the DPM2 coding region (resulting in Gly10Glu amino acid change) in Lec15.1 CHO cells causes drastically reduced DPM2 protein expression and poorly corrects the Lec15.1 phenotype (DPM synthase deficiency), whereas wild-type DPM2 restores activity. DPM1 sequence is identical in wild-type and Lec15.1 cells and DPM1 transfection does not rescue the phenotype.\",\n      \"method\": \"Sequencing of DPM2 gene; transfection/complementation assay; western blot of DPM2 protein levels; DPM synthase activity assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complementation assay with protein quantification and activity measurement, single lab, two orthogonal methods\",\n      \"pmids\": [\"14680801\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DPM2 is an 84-amino acid ER-resident membrane protein that forms an obligate regulatory subunit of the trimeric human DPM (dolichol-phosphate-mannose) synthase complex (DPM1–DPM2–DPM3): it stabilizes DPM3, which in turn stabilizes the catalytic subunit DPM1 in the ER, enhances DPM1's dolichol phosphate binding, and boosts DPM synthase enzymatic activity ~10-fold; additionally, DPM2 associates with GPI-N-acetylglucosaminyltransferase (via PIG-A, PIG-C, and GPI1) and enhances its activity ~3-fold, thereby co-regulating two key glycosylation pathways.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DPM2 is an ER-resident membrane protein that functions as an obligate regulatory subunit of the human dolichol-phosphate-mannose (DPM) synthase complex, coordinating two distinct glycosylation pathways [#0, #2]. Within the trimeric DPM synthase, DPM2 stabilizes DPM3, which in turn stabilizes the catalytic subunit DPM1 in the ER; DPM3 bridges the complex by binding DPM1 through its C-terminal domain and DPM2 through its N-terminal portion [#1]. DPM2 is required for correct ER localization and stable expression of DPM1 and enhances DPM1's binding of its dolichol phosphate substrate, raising overall DPM synthase activity roughly 10-fold, while DPM1 itself carries the catalytic function [#0, #1]. Beyond DPM synthase, DPM2 associates with GPI-N-acetylglucosaminyltransferase via the PIG-A, PIG-C, and GPI1 subunits and enhances its activity ~3-fold, though it is dispensable for early GPI intermediate synthesis, marking DPM2 as a shared co-regulator of DPM synthesis and GPI anchor biosynthesis [#2]. A G29A point mutation producing a Gly10Glu substitution sharply reduces DPM2 protein levels and fails to restore DPM synthase activity, demonstrating that DPM2 abundance is rate-limiting for complex function [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established that DPM synthase is not a single enzyme but requires a second ER protein, defining DPM2 as a regulatory partner that controls the localization, stability, and substrate binding of the catalytic DPM1.\",\n      \"evidence\": \"Expression cloning in DPM2-null Lec15 CHO cells with Co-IP, ER fractionation, dolichol phosphate binding and DPM synthase assays, plus rescue by an ER-anchored DPM1 fusion protein\",\n      \"pmids\": [\"9724629\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the full subunit composition of the complex\", \"Mechanism by which DPM2 enhances dolichol phosphate binding not structurally defined\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Resolved the DPM synthase as a three-subunit complex and ordered the stabilization hierarchy, showing DPM2 acts upstream of DPM3, which directly stabilizes catalytic DPM1.\",\n      \"evidence\": \"Reciprocal Co-IP and domain mapping of DPM3 interactions, genetic complementation in Lec15 cells, and DPM synthase activity assays\",\n      \"pmids\": [\"10835346\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the DPM1-DPM2-DPM3 assembly\", \"Stoichiometry of the trimeric complex not determined\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Extended DPM2's role beyond mannose donor synthesis by showing it physically associates with and enhances GPI-N-acetylglucosaminyltransferase, positioning DPM2 as a shared regulator across two glycosylation pathways.\",\n      \"evidence\": \"Co-IP of DPM2 with PIG-A, PIG-C and GPI1, GPI-GnT activity assays in Lec15 versus wild-type cells, and analysis of GPI biosynthesis intermediates\",\n      \"pmids\": [\"10944123\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"DPM2 is non-essential for GPI-GnT, so its precise contribution to GPI anchor output is unclear\", \"Whether DPM2 simultaneously engages both complexes or partitions between them is unknown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrated that DPM2 protein abundance is rate-limiting by linking a coding point mutation to loss of DPM2 expression and failure to restore DPM synthase activity.\",\n      \"evidence\": \"Sequencing of the DPM2 gene in Lec15.1 cells, complementation transfection, western blot quantification, and DPM synthase activity assay\",\n      \"pmids\": [\"14680801\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab with two orthogonal methods\", \"Whether the Gly10Glu change disrupts folding, membrane insertion, or partner binding was not dissected\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of how DPM2 stabilizes its partners and enhances substrate binding, and its potential role in human congenital disorders of glycosylation, remains unaddressed in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of the DPM synthase complex\", \"No human disease mutation directly characterized in the timeline\", \"Regulation of DPM2 expression and turnover not studied\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\"DPM synthase (DPM1-DPM2-DPM3)\", \"GPI-N-acetylglucosaminyltransferase\"],\n    \"partners\": [\"DPM1\", \"DPM3\", \"PIGA\", \"PIGC\", \"GPI1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}