{"gene":"SRGAP2B","run_date":"2026-06-10T07:46:41","timeline":{"discoveries":[{"year":2012,"finding":"SRGAP2B is a partial, truncated duplication of SRGAP2A encoding only a truncated F-BAR domain; it arose ~3.4 million years ago by incomplete segmental duplication of the promoter and first nine exons of SRGAP2A from 1q32.1 to 1q21.1.","method":"Sequence and comparative genomic analysis using haploid hydatidiform mole to identify duplicated sequences","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — independently reported in two concurrent Cell papers (PMID:22559943, PMID:22559944) using orthogonal genomic and expression methods","pmids":["22559943","22559944"],"is_preprint":false},{"year":2012,"finding":"SRGAP2C (derived from SRGAP2B) dimerizes with ancestral SRGAP2A to inhibit its function; expression of SRGAP2C phenocopies SRGAP2A deficiency in the mouse neocortex, leading to sustained radial migration, neoteny during spine maturation, and increased density of longer spines.","method":"Co-immunoprecipitation (dimerization), in utero electroporation/mouse neocortex expression with morphological readouts","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP for dimerization plus in vivo loss-of-function and gain-of-function with defined morphological phenotypes, replicated across two concurrent papers","pmids":["22559944","22559943"],"is_preprint":false},{"year":2019,"finding":"SRGAP2B protein is intrinsically unstable in neurons and, upon heterodimerization with SRGAP2A, reduces SRGAP2A protein levels in a proteasome-dependent manner; however, unlike SRGAP2C, SRGAP2B lacks non-synonymous mutations targeting arginine residues and cannot induce long-lasting changes in synaptic density, making it functionally distinct from SRGAP2C.","method":"Co-immunoprecipitation (heterodimerization), proteasome inhibitor treatment, live-cell imaging of protein stability, synaptic density assays in cortical neurons","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, proteasome inhibition, synaptic phenotype) from single lab","pmids":["31822692"],"is_preprint":false},{"year":2024,"finding":"SRGAP2B/C are required for synaptic neoteny in human cortical pyramidal neurons: downregulation of SRGAP2B/C accelerated synaptic development; mechanistically, SRGAP2B/C reduce synaptic levels of SRGAP2A, thereby increasing postsynaptic accumulation of SYNGAP1; the tempo of synaptogenesis is set by reciprocal antagonism between SRGAP2A and SYNGAP1, tipped toward neoteny by SRGAP2B/C.","method":"shRNA knockdown of SRGAP2B/C in human cortical neurons xenotransplanted in mouse cortex, combinatorial loss-of-function in vivo, synaptic protein quantification","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo epistasis via combinatorial loss-of-function, direct protein-level quantification, xenotransplantation model with defined molecular readouts","pmids":["39406239"],"is_preprint":false},{"year":2024,"finding":"SRGAP2B/C are expressed in human microglia (not only cortical neurons) and are necessary and sufficient, in a cell-autonomous manner, to induce neotenic features of microglia structural and functional maturation; additionally, SRGAP2B/C-dependent neotenic changes in microglia non-cell-autonomously impact synaptic development in cortical pyramidal neurons.","method":"Xenotransplantation of hiPSC-derived microglia into mouse brain, mouse genetic models, loss-of-function and gain-of-function experiments with structural and functional readouts","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo xenotransplantation plus mouse genetic models, multiple readouts, single lab, preprint not yet peer-reviewed","pmids":["38979266"],"is_preprint":true}],"current_model":"SRGAP2B is a human-specific truncated paralog of SRGAP2A encoding only a partial F-BAR domain; it heterodimerizes with SRGAP2A to destabilize it via the proteasome, thereby reducing SRGAP2A synaptic levels, increasing postsynaptic SYNGAP1 accumulation, and—together with SRGAP2C—inducing neoteny of both cortical neuron and microglial maturation, though SRGAP2B lacks specific arginine-targeting mutations present in SRGAP2C and cannot alone sustain long-lasting changes in synaptic density."},"narrative":{"mechanistic_narrative":"SRGAP2B is a human-specific, partially truncated segmental duplication of the ancestral SRGAP2A gene that arose ~3.4 million years ago and encodes only a truncated F-BAR domain [PMID:22559943, PMID:22559944]. It acts as an antagonist of its ancestral paralog: SRGAP2B protein is intrinsically unstable in neurons and, upon heterodimerization with SRGAP2A, drives proteasome-dependent reduction of SRGAP2A protein levels [PMID:31822692]. Through this lowering of synaptic SRGAP2A, SRGAP2B together with SRGAP2C increases postsynaptic accumulation of SYNGAP1, and the resulting shift in the reciprocal SRGAP2A–SYNGAP1 antagonism sets a slowed (neotenic) tempo of human cortical synaptogenesis [PMID:39406239]. SRGAP2B/C also act in human microglia to induce neotenic structural and functional maturation that non-cell-autonomously influences cortical synaptic development [PMID:38979266]. SRGAP2B is functionally distinct from the closely related SRGAP2C: it lacks the arginine-targeting non-synonymous substitutions present in SRGAP2C and cannot by itself sustain long-lasting changes in synaptic density [PMID:31822692].","teleology":[{"year":2012,"claim":"Established the origin and structure of SRGAP2B, explaining how a human-specific paralog encoding only a partial F-BAR domain could exist as a candidate modifier of SRGAP2A function.","evidence":"Comparative genomic and sequence analysis using a haploid hydatidiform mole to resolve duplicated segments","pmids":["22559943","22559944"],"confidence":"High","gaps":["Did not establish whether the truncated SRGAP2B protein itself is functional or merely a dominant-negative fragment","Did not directly test SRGAP2B-SRGAP2A interaction biochemically"]},{"year":2012,"claim":"Showed that the SRGAP2B-derived paralog SRGAP2C dimerizes with and inhibits ancestral SRGAP2A, linking the duplication to neuronal phenotypes of migration and spine neoteny.","evidence":"Co-immunoprecipitation for dimerization plus in utero electroporation in mouse neocortex with morphological readouts","pmids":["22559944","22559943"],"confidence":"High","gaps":["Focused on SRGAP2C; did not resolve the distinct contribution of SRGAP2B","Mechanism by which dimerization inhibits SRGAP2A activity not defined at this stage"]},{"year":2019,"claim":"Defined the molecular mechanism of SRGAP2B antagonism and distinguished it from SRGAP2C, answering how a truncated paralog lowers ancestral protein activity.","evidence":"Co-IP heterodimerization, proteasome inhibitor treatment, live-cell protein stability imaging and synaptic density assays in cortical neurons","pmids":["31822692"],"confidence":"Medium","gaps":["From a single lab; reciprocal in vivo validation of the proteasome-dependent destabilization limited","Did not identify the E3 ligase or degron mediating SRGAP2A turnover","Did not resolve why SRGAP2B alone cannot sustain synaptic density changes at the molecular level"]},{"year":2024,"claim":"Placed SRGAP2B/C within a defined synaptic signaling axis, showing that lowering SRGAP2A raises postsynaptic SYNGAP1 and that this antagonism sets the tempo of human synaptogenesis.","evidence":"shRNA knockdown and combinatorial loss-of-function of SRGAP2B/C in human cortical neurons xenotransplanted into mouse cortex, with synaptic protein quantification and in vivo epistasis","pmids":["39406239"],"confidence":"High","gaps":["SRGAP2B and SRGAP2C contributions assayed jointly, not separated","Direct biochemical link between SRGAP2A reduction and SYNGAP1 accumulation not fully resolved"]},{"year":2024,"claim":"Extended SRGAP2B/C function beyond neurons, showing a cell-autonomous role in microglial neoteny that feeds back onto cortical synaptic development.","evidence":"Xenotransplantation of hiPSC-derived microglia into mouse brain plus mouse genetic loss- and gain-of-function with structural and functional readouts (preprint)","pmids":["38979266"],"confidence":"Medium","gaps":["Preprint, not yet peer-reviewed","Distinct role of SRGAP2B versus SRGAP2C in microglia not separated","Molecular mediators of the non-cell-autonomous effect on synapses unknown"]},{"year":null,"claim":"How SRGAP2B's heterodimerization is converted into SRGAP2A proteasomal degradation, and what distinguishes its transient effects from the durable effects of SRGAP2C at the molecular level, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No E3 ligase or degron identified for SRGAP2A turnover","No structural model of the SRGAP2B-SRGAP2A heterodimer","SRGAP2B-specific (versus SRGAP2C) contributions to neuronal and microglial neoteny not isolated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[3]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[3,4]}],"complexes":[],"partners":["SRGAP2A"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P0DMP2","full_name":"SLIT-ROBO Rho GTPase-activating protein 2B","aliases":["SLIT-ROBO Rho GTPase activating protein 2 pseudogene 2"],"length_aa":458,"mass_kda":53.4,"function":"May regulate cell migration and differentiation through interaction with and inhibition of SRGAP2 (PubMed:31822692). In contrast to SRGAP2C, it is not able to induce long-lasting changes in synaptic density throughout adulthood (PubMed:31822692)","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/P0DMP2/entry"},"depmap":{"release":"DepMap","has_data":false,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SRGAP2B"},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SRGAP2B","total_profiled":1310},"omim":[{"mim_id":"614705","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 2D; SRGAP2D","url":"https://www.omim.org/entry/614705"},{"mim_id":"614704","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 2C; SRGAP2C","url":"https://www.omim.org/entry/614704"},{"mim_id":"614703","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 2B; SRGAP2B","url":"https://www.omim.org/entry/614703"},{"mim_id":"606524","title":"SLIT-ROBO RHO GTPase-ACTIVATING PROTEIN 2; SRGAP2","url":"https://www.omim.org/entry/606524"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Centrosome","reliability":"Approved"},{"location":"Basal body","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"brain","ntpm":55.9},{"tissue":"skin 1","ntpm":15.1}],"url":"https://www.proteinatlas.org/search/SRGAP2B"},"hgnc":{"alias_symbol":[],"prev_symbol":["SRGAP2P2"]},"alphafold":{"accession":"P0DMP2","domains":[{"cath_id":"1.20.1270.60","chopping":"11-82_90-197_223-311","consensus_level":"high","plddt":93.8586,"start":11,"end":311},{"cath_id":"-","chopping":"361-404_427-458","consensus_level":"medium","plddt":90.5443,"start":361,"end":458}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P0DMP2","model_url":"https://alphafold.ebi.ac.uk/files/AF-P0DMP2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P0DMP2-F1-predicted_aligned_error_v6.png","plddt_mean":88.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SRGAP2B","jax_strain_url":"https://www.jax.org/strain/search?query=SRGAP2B"},"sequence":{"accession":"P0DMP2","fasta_url":"https://rest.uniprot.org/uniprotkb/P0DMP2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P0DMP2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P0DMP2"}},"corpus_meta":[{"pmid":"22559944","id":"PMC_22559944","title":"Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22559944","citation_count":328,"is_preprint":false},{"pmid":"22559943","id":"PMC_22559943","title":"Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22559943","citation_count":296,"is_preprint":false},{"pmid":"31822692","id":"PMC_31822692","title":"The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31822692","citation_count":50,"is_preprint":false},{"pmid":"31096545","id":"PMC_31096545","title":"Identification and Characterization of Novel Fusion Genes with Potential Clinical Applications in Mexican Children with Acute Lymphoblastic Leukemia.","date":"2019","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31096545","citation_count":16,"is_preprint":false},{"pmid":"39406239","id":"PMC_39406239","title":"Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition.","date":"2024","source":"Neuron","url":"https://pubmed.ncbi.nlm.nih.gov/39406239","citation_count":14,"is_preprint":false},{"pmid":"38979266","id":"PMC_38979266","title":"Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38979266","citation_count":4,"is_preprint":false},{"pmid":"41273738","id":"PMC_41273738","title":"Descriptive transcriptomic profiling differentiates oral leukoplakia from proliferative verrucous leukoplakia and reveals distinct molecular signatures.","date":"2026","source":"Medicina oral, patologia oral y cirugia bucal","url":"https://pubmed.ncbi.nlm.nih.gov/41273738","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5399,"output_tokens":1427,"usd":0.018801,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8103,"output_tokens":2250,"usd":0.048383,"stage2_stop_reason":"end_turn"},"total_usd":0.067184,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2012,\n      \"finding\": \"SRGAP2B is a partial, truncated duplication of SRGAP2A encoding only a truncated F-BAR domain; it arose ~3.4 million years ago by incomplete segmental duplication of the promoter and first nine exons of SRGAP2A from 1q32.1 to 1q21.1.\",\n      \"method\": \"Sequence and comparative genomic analysis using haploid hydatidiform mole to identify duplicated sequences\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — independently reported in two concurrent Cell papers (PMID:22559943, PMID:22559944) using orthogonal genomic and expression methods\",\n      \"pmids\": [\"22559943\", \"22559944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"SRGAP2C (derived from SRGAP2B) dimerizes with ancestral SRGAP2A to inhibit its function; expression of SRGAP2C phenocopies SRGAP2A deficiency in the mouse neocortex, leading to sustained radial migration, neoteny during spine maturation, and increased density of longer spines.\",\n      \"method\": \"Co-immunoprecipitation (dimerization), in utero electroporation/mouse neocortex expression with morphological readouts\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP for dimerization plus in vivo loss-of-function and gain-of-function with defined morphological phenotypes, replicated across two concurrent papers\",\n      \"pmids\": [\"22559944\", \"22559943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SRGAP2B protein is intrinsically unstable in neurons and, upon heterodimerization with SRGAP2A, reduces SRGAP2A protein levels in a proteasome-dependent manner; however, unlike SRGAP2C, SRGAP2B lacks non-synonymous mutations targeting arginine residues and cannot induce long-lasting changes in synaptic density, making it functionally distinct from SRGAP2C.\",\n      \"method\": \"Co-immunoprecipitation (heterodimerization), proteasome inhibitor treatment, live-cell imaging of protein stability, synaptic density assays in cortical neurons\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (Co-IP, proteasome inhibition, synaptic phenotype) from single lab\",\n      \"pmids\": [\"31822692\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SRGAP2B/C are required for synaptic neoteny in human cortical pyramidal neurons: downregulation of SRGAP2B/C accelerated synaptic development; mechanistically, SRGAP2B/C reduce synaptic levels of SRGAP2A, thereby increasing postsynaptic accumulation of SYNGAP1; the tempo of synaptogenesis is set by reciprocal antagonism between SRGAP2A and SYNGAP1, tipped toward neoteny by SRGAP2B/C.\",\n      \"method\": \"shRNA knockdown of SRGAP2B/C in human cortical neurons xenotransplanted in mouse cortex, combinatorial loss-of-function in vivo, synaptic protein quantification\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo epistasis via combinatorial loss-of-function, direct protein-level quantification, xenotransplantation model with defined molecular readouts\",\n      \"pmids\": [\"39406239\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SRGAP2B/C are expressed in human microglia (not only cortical neurons) and are necessary and sufficient, in a cell-autonomous manner, to induce neotenic features of microglia structural and functional maturation; additionally, SRGAP2B/C-dependent neotenic changes in microglia non-cell-autonomously impact synaptic development in cortical pyramidal neurons.\",\n      \"method\": \"Xenotransplantation of hiPSC-derived microglia into mouse brain, mouse genetic models, loss-of-function and gain-of-function experiments with structural and functional readouts\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo xenotransplantation plus mouse genetic models, multiple readouts, single lab, preprint not yet peer-reviewed\",\n      \"pmids\": [\"38979266\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SRGAP2B is a human-specific truncated paralog of SRGAP2A encoding only a partial F-BAR domain; it heterodimerizes with SRGAP2A to destabilize it via the proteasome, thereby reducing SRGAP2A synaptic levels, increasing postsynaptic SYNGAP1 accumulation, and—together with SRGAP2C—inducing neoteny of both cortical neuron and microglial maturation, though SRGAP2B lacks specific arginine-targeting mutations present in SRGAP2C and cannot alone sustain long-lasting changes in synaptic density.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRGAP2B is a human-specific, partially truncated segmental duplication of the ancestral SRGAP2A gene that arose ~3.4 million years ago and encodes only a truncated F-BAR domain [#0]. It acts as an antagonist of its ancestral paralog: SRGAP2B protein is intrinsically unstable in neurons and, upon heterodimerization with SRGAP2A, drives proteasome-dependent reduction of SRGAP2A protein levels [#2]. Through this lowering of synaptic SRGAP2A, SRGAP2B together with SRGAP2C increases postsynaptic accumulation of SYNGAP1, and the resulting shift in the reciprocal SRGAP2A–SYNGAP1 antagonism sets a slowed (neotenic) tempo of human cortical synaptogenesis [#3]. SRGAP2B/C also act in human microglia to induce neotenic structural and functional maturation that non-cell-autonomously influences cortical synaptic development [#4]. SRGAP2B is functionally distinct from the closely related SRGAP2C: it lacks the arginine-targeting non-synonymous substitutions present in SRGAP2C and cannot by itself sustain long-lasting changes in synaptic density [#2].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Established the origin and structure of SRGAP2B, explaining how a human-specific paralog encoding only a partial F-BAR domain could exist as a candidate modifier of SRGAP2A function.\",\n      \"evidence\": \"Comparative genomic and sequence analysis using a haploid hydatidiform mole to resolve duplicated segments\",\n      \"pmids\": [\"22559943\", \"22559944\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Did not establish whether the truncated SRGAP2B protein itself is functional or merely a dominant-negative fragment\",\n        \"Did not directly test SRGAP2B-SRGAP2A interaction biochemically\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed that the SRGAP2B-derived paralog SRGAP2C dimerizes with and inhibits ancestral SRGAP2A, linking the duplication to neuronal phenotypes of migration and spine neoteny.\",\n      \"evidence\": \"Co-immunoprecipitation for dimerization plus in utero electroporation in mouse neocortex with morphological readouts\",\n      \"pmids\": [\"22559944\", \"22559943\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Focused on SRGAP2C; did not resolve the distinct contribution of SRGAP2B\",\n        \"Mechanism by which dimerization inhibits SRGAP2A activity not defined at this stage\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined the molecular mechanism of SRGAP2B antagonism and distinguished it from SRGAP2C, answering how a truncated paralog lowers ancestral protein activity.\",\n      \"evidence\": \"Co-IP heterodimerization, proteasome inhibitor treatment, live-cell protein stability imaging and synaptic density assays in cortical neurons\",\n      \"pmids\": [\"31822692\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"From a single lab; reciprocal in vivo validation of the proteasome-dependent destabilization limited\",\n        \"Did not identify the E3 ligase or degron mediating SRGAP2A turnover\",\n        \"Did not resolve why SRGAP2B alone cannot sustain synaptic density changes at the molecular level\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placed SRGAP2B/C within a defined synaptic signaling axis, showing that lowering SRGAP2A raises postsynaptic SYNGAP1 and that this antagonism sets the tempo of human synaptogenesis.\",\n      \"evidence\": \"shRNA knockdown and combinatorial loss-of-function of SRGAP2B/C in human cortical neurons xenotransplanted into mouse cortex, with synaptic protein quantification and in vivo epistasis\",\n      \"pmids\": [\"39406239\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"SRGAP2B and SRGAP2C contributions assayed jointly, not separated\",\n        \"Direct biochemical link between SRGAP2A reduction and SYNGAP1 accumulation not fully resolved\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended SRGAP2B/C function beyond neurons, showing a cell-autonomous role in microglial neoteny that feeds back onto cortical synaptic development.\",\n      \"evidence\": \"Xenotransplantation of hiPSC-derived microglia into mouse brain plus mouse genetic loss- and gain-of-function with structural and functional readouts (preprint)\",\n      \"pmids\": [\"38979266\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint, not yet peer-reviewed\",\n        \"Distinct role of SRGAP2B versus SRGAP2C in microglia not separated\",\n        \"Molecular mediators of the non-cell-autonomous effect on synapses unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SRGAP2B's heterodimerization is converted into SRGAP2A proteasomal degradation, and what distinguishes its transient effects from the durable effects of SRGAP2C at the molecular level, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No E3 ligase or degron identified for SRGAP2A turnover\",\n        \"No structural model of the SRGAP2B-SRGAP2A heterodimer\",\n        \"SRGAP2B-specific (versus SRGAP2C) contributions to neuronal and microglial neoteny not isolated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"SRGAP2A\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}