{"gene":"FRA10AC1","run_date":"2026-06-09T23:54:44","timeline":{"discoveries":[{"year":2004,"finding":"FRA10AC1 encodes a nuclear protein that localizes exclusively to the nucleoplasm, as demonstrated by immunofluorescence of full-length recombinant EGFP-tagged FRA10AC1. The FRA10A fragile site is caused by expansion and subsequent methylation of a CGG trinucleotide repeat in the 5'UTR of FRA10AC1, silencing transcription of the affected allele.","method":"Immunofluorescence of EGFP-tagged FRA10AC1; sequence analysis; methylation analysis; cSNP allele-specific expression assay","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with EGFP fusion and allele-specific expression confirmed by cSNPs; single lab but multiple orthogonal methods","pmids":["15203205"],"is_preprint":false},{"year":2022,"finding":"FRA10AC1 is a peripheral protein of the spliceosomal C complex. Co-immunoprecipitation of ectopically expressed HA-FRA10AC1 pulled down endogenous DGCR14 (another spliceosomal C complex component), but not CHERP, NKAP, RED, or SF3B2. The p.Glu165del variant impairs intrinsic protein stability but does not affect nuclear localization. Loss-of-function variants result in drastically reduced or absent FRA10AC1 transcript and protein in patient fibroblasts.","method":"Co-immunoprecipitation; in vitro splicing reporter assay; heterologous expression with stability assessment; immunofluorescence for localization; western blot/RT-PCR in patient fibroblasts","journal":"Brain : a journal of neurology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP identifying specific binding partner (DGCR14) with negative controls for non-interactors, combined with functional stability assay and patient-derived fibroblast validation; multiple orthogonal methods in a single rigorous study","pmids":["34694367"],"is_preprint":false},{"year":2022,"finding":"In vitro splicing reporter assay in patient-derived fibroblasts lacking FRA10AC1 did not provide evidence that FRA10AC1 deficiency suppresses missplicing caused by mutations in highly conserved dinucleotides of 5' and 3' splice sites, indicating FRA10AC1 is not required for this specific aspect of splice-site recognition.","method":"In vitro splicing reporter assay in patient-derived FRA10AC1-deficient fibroblasts","journal":"Brain : a journal of neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — controlled functional assay with loss-of-function patient cells; single lab, negative result mechanistically informative","pmids":["34694367"],"is_preprint":false},{"year":2023,"finding":"FRA10AC1 directly interacts with ESS2 (DGCR14), a non-core spliceosomal protein; their interacting domains were mapped and their physical interaction confirmed at the level of intracellular protein stoichiometries by co-immunoprecipitation. Endogenous FRA10AC1 and SF3B2 (a core spliceosomal protein) failed to co-immunoprecipitate, despite an earlier in vitro interaction report.","method":"Co-immunoprecipitation of endogenous proteins; domain-mapping experiments; tissue co-localization analysis","journal":"Genes","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with domain mapping confirming FRA10AC1–ESS2 interaction and a clear negative result for SF3B2; single lab","pmids":["36980839"],"is_preprint":false},{"year":2026,"finding":"A homozygous splice-site variant in FRA10AC1 (c.465+1G>A) was confirmed by mRNA analysis to cause exon 7 skipping and early protein truncation (p.Trp127CysfsTer8), establishing a loss-of-function mechanism for this variant.","method":"mRNA analysis (RT-PCR with exon skipping confirmation); exome sequencing","journal":"Journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct mRNA-level confirmation of splice defect; single case/single lab","pmids":["41571908"],"is_preprint":false}],"current_model":"FRA10AC1 encodes a conserved nuclear protein that is a peripheral component of the spliceosomal C complex, where it directly binds DGCR14/ESS2 (but not SF3B2 under endogenous conditions); its expression is silenced by CGG-repeat expansion and methylation at the FRA10A fragile site, and biallelic loss-of-function variants cause a neurodevelopmental syndrome with growth retardation, though its precise catalytic or regulatory role within the spliceosome remains incompletely defined."},"narrative":{"mechanistic_narrative":"FRA10AC1 encodes a conserved nucleoplasmic protein that functions as a peripheral component of the spliceosomal C complex [PMID:15203205, PMID:34694367]. Within the spliceosome it directly engages the non-core component DGCR14/ESS2, an interaction confirmed by reciprocal co-immunoprecipitation at endogenous protein stoichiometries and refined by domain mapping; under endogenous conditions it does not associate with the core component SF3B2 or with CHERP, NKAP, or RED [PMID:34694367, PMID:36980839]. Loss of FRA10AC1 does not rescue missplicing caused by mutations at conserved 5' and 3' splice-site dinucleotides, indicating it is not required for this aspect of splice-site recognition and that its specific catalytic or regulatory role in splicing remains undefined [PMID:34694367]. Transcription of FRA10AC1 is silenced by expansion and methylation of a CGG repeat in its 5'UTR at the FRA10A fragile site [PMID:15203205], and biallelic loss-of-function variants—including a stability-impairing in-frame deletion and splice-site variants that truncate the protein—cause a neurodevelopmental syndrome with growth retardation through reduced or absent transcript and protein [PMID:34694367, PMID:41571908].","teleology":[{"year":2004,"claim":"Establishing where FRA10AC1 acts and how the FRA10A fragile site disrupts it answered whether this gene product is nuclear and how repeat expansion silences it.","evidence":"Immunofluorescence of EGFP-tagged FRA10AC1, methylation analysis, and allele-specific expression assays","pmids":["15203205"],"confidence":"Medium","gaps":["Localization shown only for an overexpressed EGFP fusion, not endogenous protein","No molecular function or interaction partner identified at this stage"]},{"year":2022,"claim":"Placing FRA10AC1 in the spliceosomal C complex and identifying DGCR14 as a specific partner answered what macromolecular machine the protein belongs to and which component it contacts.","evidence":"Co-immunoprecipitation of HA-FRA10AC1 with negative controls, stability assessment of the p.Glu165del variant, and patient-fibroblast western blot/RT-PCR","pmids":["34694367"],"confidence":"High","gaps":["The catalytic or regulatory contribution of FRA10AC1 to splicing not defined","DGCR14 interaction not yet domain-mapped at this stage"]},{"year":2022,"claim":"Testing whether FRA10AC1 loss alters splice-site recognition addressed its functional requirement in core splicing, returning a negative that narrows its role.","evidence":"In vitro splicing reporter assay in FRA10AC1-deficient patient fibroblasts","pmids":["34694367"],"confidence":"Medium","gaps":["Does not identify which splicing events, if any, depend on FRA10AC1","Negative result for one assay does not exclude other splicing roles"]},{"year":2023,"claim":"Mapping the FRA10AC1–ESS2 interaction domains and re-testing the SF3B2 association resolved the direct binding partner and excluded a previously reported core-spliceosome contact under endogenous conditions.","evidence":"Co-immunoprecipitation of endogenous proteins, domain mapping, and tissue co-localization analysis","pmids":["36980839"],"confidence":"Medium","gaps":["Functional consequence of the FRA10AC1–ESS2 interaction unknown","Single-lab study without structural confirmation of mapped domains"]},{"year":2026,"claim":"Confirming that a homozygous splice-site variant produces exon skipping and truncation extended the loss-of-function disease mechanism to an additional allele.","evidence":"mRNA RT-PCR confirmation of exon 7 skipping and exome sequencing of a single case","pmids":["41571908"],"confidence":"Medium","gaps":["Single case without functional rescue","Does not connect the molecular splicing role of FRA10AC1 to the disease phenotype"]},{"year":null,"claim":"The precise catalytic or regulatory function of FRA10AC1 within the spliceosomal C complex, and the mechanism linking its loss to neurodevelopmental and growth phenotypes, remain unresolved.","evidence":"No timeline discovery defines a substrate, enzymatic activity, or mechanistic link to phenotype","pmids":[],"confidence":"Low","gaps":["No defined molecular activity within the spliceosome","No structural model of FRA10AC1 or its DGCR14/ESS2 contact","Mechanism connecting splicing role to disease phenotype unestablished"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[1,3]}],"complexes":["spliceosomal C complex"],"partners":["DGCR14"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q70Z53","full_name":"Protein FRA10AC1","aliases":[],"length_aa":315,"mass_kda":37.5,"function":"May be involved in pre-mRNA splicing","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q70Z53/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FRA10AC1","classification":"Not Classified","n_dependent_lines":8,"n_total_lines":1208,"dependency_fraction":0.006622516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"UBA1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/FRA10AC1","total_profiled":1310},"omim":[{"mim_id":"620113","title":"NEURODEVELOPMENTAL DISORDER WITH GROWTH RETARDATION, DYSMORPHIC FACIES, AND CORPUS CALLOSUM ABNORMALITIES; NEDGFC","url":"https://www.omim.org/entry/620113"},{"mim_id":"608866","title":"FRA10A-ASSOCIATED CGG REPEAT 1; FRA10AC1","url":"https://www.omim.org/entry/608866"}],"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/FRA10AC1"},"hgnc":{"alias_symbol":[],"prev_symbol":["C10orf4"]},"alphafold":{"accession":"Q70Z53","domains":[{"cath_id":"-","chopping":"103-139","consensus_level":"medium","plddt":85.3062,"start":103,"end":139},{"cath_id":"-","chopping":"140-228","consensus_level":"medium","plddt":88.673,"start":140,"end":228},{"cath_id":"1.10.287","chopping":"51-94","consensus_level":"medium","plddt":86.79,"start":51,"end":94}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q70Z53","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q70Z53-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q70Z53-F1-predicted_aligned_error_v6.png","plddt_mean":72.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FRA10AC1","jax_strain_url":"https://www.jax.org/strain/search?query=FRA10AC1"},"sequence":{"accession":"Q70Z53","fasta_url":"https://rest.uniprot.org/uniprotkb/Q70Z53.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q70Z53/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q70Z53"}},"corpus_meta":[{"pmid":"15203205","id":"PMC_15203205","title":"Folate-sensitive fragile site FRA10A is due to an expansion of a CGG repeat in a novel gene, FRA10AC1, encoding a nuclear protein.","date":"2004","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/15203205","citation_count":52,"is_preprint":false},{"pmid":"26252872","id":"PMC_26252872","title":"Variations in the FRA10AC1 Fragile Site and 15q21 Are Associated with Cerebrospinal Fluid Aβ1-42 Level.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26252872","citation_count":36,"is_preprint":false},{"pmid":"34694367","id":"PMC_34694367","title":"Biallelic FRA10AC1 variants cause a neurodevelopmental disorder with growth retardation.","date":"2022","source":"Brain : a journal of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/34694367","citation_count":16,"is_preprint":false},{"pmid":"37768318","id":"PMC_37768318","title":"Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions.","date":"2023","source":"Emerging topics in life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37768318","citation_count":10,"is_preprint":false},{"pmid":"35821753","id":"PMC_35821753","title":"A Biallelic Variant in FRA10AC1 Is Associated With Neurodevelopmental Disorder and Growth Retardation.","date":"2022","source":"Neurology. Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/35821753","citation_count":5,"is_preprint":false},{"pmid":"23900196","id":"PMC_23900196","title":"Unraveling microalgal molecular interactions using evolutionary and structural bioinformatics.","date":"2013","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/23900196","citation_count":5,"is_preprint":false},{"pmid":"36980839","id":"PMC_36980839","title":"Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease.","date":"2023","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/36980839","citation_count":3,"is_preprint":false},{"pmid":"39528289","id":"PMC_39528289","title":"[Clinical phenotype and genetic analysis of a child with partial duplication of 10q and a literature review].","date":"2024","source":"Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39528289","citation_count":1,"is_preprint":false},{"pmid":"41571908","id":"PMC_41571908","title":"A novel homozygous splicing variant in FRA10AC1: further delineation of the phenotype.","date":"2026","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/41571908","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7007,"output_tokens":1396,"usd":0.02098,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8076,"output_tokens":2006,"usd":0.045265,"stage2_stop_reason":"end_turn"},"total_usd":0.066245,"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\": 2004,\n      \"finding\": \"FRA10AC1 encodes a nuclear protein that localizes exclusively to the nucleoplasm, as demonstrated by immunofluorescence of full-length recombinant EGFP-tagged FRA10AC1. The FRA10A fragile site is caused by expansion and subsequent methylation of a CGG trinucleotide repeat in the 5'UTR of FRA10AC1, silencing transcription of the affected allele.\",\n      \"method\": \"Immunofluorescence of EGFP-tagged FRA10AC1; sequence analysis; methylation analysis; cSNP allele-specific expression assay\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with EGFP fusion and allele-specific expression confirmed by cSNPs; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"15203205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"FRA10AC1 is a peripheral protein of the spliceosomal C complex. Co-immunoprecipitation of ectopically expressed HA-FRA10AC1 pulled down endogenous DGCR14 (another spliceosomal C complex component), but not CHERP, NKAP, RED, or SF3B2. The p.Glu165del variant impairs intrinsic protein stability but does not affect nuclear localization. Loss-of-function variants result in drastically reduced or absent FRA10AC1 transcript and protein in patient fibroblasts.\",\n      \"method\": \"Co-immunoprecipitation; in vitro splicing reporter assay; heterologous expression with stability assessment; immunofluorescence for localization; western blot/RT-PCR in patient fibroblasts\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP identifying specific binding partner (DGCR14) with negative controls for non-interactors, combined with functional stability assay and patient-derived fibroblast validation; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"34694367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In vitro splicing reporter assay in patient-derived fibroblasts lacking FRA10AC1 did not provide evidence that FRA10AC1 deficiency suppresses missplicing caused by mutations in highly conserved dinucleotides of 5' and 3' splice sites, indicating FRA10AC1 is not required for this specific aspect of splice-site recognition.\",\n      \"method\": \"In vitro splicing reporter assay in patient-derived FRA10AC1-deficient fibroblasts\",\n      \"journal\": \"Brain : a journal of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — controlled functional assay with loss-of-function patient cells; single lab, negative result mechanistically informative\",\n      \"pmids\": [\"34694367\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FRA10AC1 directly interacts with ESS2 (DGCR14), a non-core spliceosomal protein; their interacting domains were mapped and their physical interaction confirmed at the level of intracellular protein stoichiometries by co-immunoprecipitation. Endogenous FRA10AC1 and SF3B2 (a core spliceosomal protein) failed to co-immunoprecipitate, despite an earlier in vitro interaction report.\",\n      \"method\": \"Co-immunoprecipitation of endogenous proteins; domain-mapping experiments; tissue co-localization analysis\",\n      \"journal\": \"Genes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with domain mapping confirming FRA10AC1–ESS2 interaction and a clear negative result for SF3B2; single lab\",\n      \"pmids\": [\"36980839\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"A homozygous splice-site variant in FRA10AC1 (c.465+1G>A) was confirmed by mRNA analysis to cause exon 7 skipping and early protein truncation (p.Trp127CysfsTer8), establishing a loss-of-function mechanism for this variant.\",\n      \"method\": \"mRNA analysis (RT-PCR with exon skipping confirmation); exome sequencing\",\n      \"journal\": \"Journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct mRNA-level confirmation of splice defect; single case/single lab\",\n      \"pmids\": [\"41571908\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FRA10AC1 encodes a conserved nuclear protein that is a peripheral component of the spliceosomal C complex, where it directly binds DGCR14/ESS2 (but not SF3B2 under endogenous conditions); its expression is silenced by CGG-repeat expansion and methylation at the FRA10A fragile site, and biallelic loss-of-function variants cause a neurodevelopmental syndrome with growth retardation, though its precise catalytic or regulatory role within the spliceosome remains incompletely defined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FRA10AC1 encodes a conserved nucleoplasmic protein that functions as a peripheral component of the spliceosomal C complex [#0, #1]. Within the spliceosome it directly engages the non-core component DGCR14/ESS2, an interaction confirmed by reciprocal co-immunoprecipitation at endogenous protein stoichiometries and refined by domain mapping; under endogenous conditions it does not associate with the core component SF3B2 or with CHERP, NKAP, or RED [#1, #3]. Loss of FRA10AC1 does not rescue missplicing caused by mutations at conserved 5' and 3' splice-site dinucleotides, indicating it is not required for this aspect of splice-site recognition and that its specific catalytic or regulatory role in splicing remains undefined [#2]. Transcription of FRA10AC1 is silenced by expansion and methylation of a CGG repeat in its 5'UTR at the FRA10A fragile site [#0], and biallelic loss-of-function variants—including a stability-impairing in-frame deletion and splice-site variants that truncate the protein—cause a neurodevelopmental syndrome with growth retardation through reduced or absent transcript and protein [#1, #4].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing where FRA10AC1 acts and how the FRA10A fragile site disrupts it answered whether this gene product is nuclear and how repeat expansion silences it.\",\n      \"evidence\": \"Immunofluorescence of EGFP-tagged FRA10AC1, methylation analysis, and allele-specific expression assays\",\n      \"pmids\": [\"15203205\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization shown only for an overexpressed EGFP fusion, not endogenous protein\",\n        \"No molecular function or interaction partner identified at this stage\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placing FRA10AC1 in the spliceosomal C complex and identifying DGCR14 as a specific partner answered what macromolecular machine the protein belongs to and which component it contacts.\",\n      \"evidence\": \"Co-immunoprecipitation of HA-FRA10AC1 with negative controls, stability assessment of the p.Glu165del variant, and patient-fibroblast western blot/RT-PCR\",\n      \"pmids\": [\"34694367\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The catalytic or regulatory contribution of FRA10AC1 to splicing not defined\",\n        \"DGCR14 interaction not yet domain-mapped at this stage\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Testing whether FRA10AC1 loss alters splice-site recognition addressed its functional requirement in core splicing, returning a negative that narrows its role.\",\n      \"evidence\": \"In vitro splicing reporter assay in FRA10AC1-deficient patient fibroblasts\",\n      \"pmids\": [\"34694367\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not identify which splicing events, if any, depend on FRA10AC1\",\n        \"Negative result for one assay does not exclude other splicing roles\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapping the FRA10AC1–ESS2 interaction domains and re-testing the SF3B2 association resolved the direct binding partner and excluded a previously reported core-spliceosome contact under endogenous conditions.\",\n      \"evidence\": \"Co-immunoprecipitation of endogenous proteins, domain mapping, and tissue co-localization analysis\",\n      \"pmids\": [\"36980839\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the FRA10AC1–ESS2 interaction unknown\",\n        \"Single-lab study without structural confirmation of mapped domains\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Confirming that a homozygous splice-site variant produces exon skipping and truncation extended the loss-of-function disease mechanism to an additional allele.\",\n      \"evidence\": \"mRNA RT-PCR confirmation of exon 7 skipping and exome sequencing of a single case\",\n      \"pmids\": [\"41571908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single case without functional rescue\",\n        \"Does not connect the molecular splicing role of FRA10AC1 to the disease phenotype\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise catalytic or regulatory function of FRA10AC1 within the spliceosomal C complex, and the mechanism linking its loss to neurodevelopmental and growth phenotypes, remain unresolved.\",\n      \"evidence\": \"No timeline discovery defines a substrate, enzymatic activity, or mechanistic link to phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No defined molecular activity within the spliceosome\",\n        \"No structural model of FRA10AC1 or its DGCR14/ESS2 contact\",\n        \"Mechanism connecting splicing role to disease phenotype unestablished\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [\"spliceosomal C complex\"],\n    \"partners\": [\"DGCR14\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}