{"gene":"FAM124B","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":2012,"finding":"FAM124B was identified as a novel component of a CHD7- and CHD8-containing chromatin remodeling complex; direct binding to the CHD8 subunit was demonstrated by yeast two-hybrid, and association with the full CHD7/CHD8 complex was confirmed by co-immunoprecipitation. FAM124B localizes predominantly to the nucleus and is expressed broadly in embryonic and adult mouse tissues.","method":"SILAC mass spectrometry, co-immunoprecipitation, direct yeast two-hybrid, immunofluorescence/subcellular fractionation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus direct yeast two-hybrid establishing direct CHD8 binding, multiple orthogonal methods in a single lab study","pmids":["23285124"],"is_preprint":false},{"year":2024,"finding":"Inhibition of FAM124B in human umbilical vein endothelial cells (HUVECs) decreased vascular endothelial cell proliferation, suggesting FAM124B plays a functional role in endothelial cell proliferation.","method":"In vitro loss-of-function experiment in HUVECs (proliferation assay)","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single in vitro knockdown experiment, single lab, no mechanistic pathway placement beyond proliferation phenotype","pmids":["39384883"],"is_preprint":false}],"current_model":"FAM124B is a predominantly nuclear protein that directly binds CHD8 and associates with a CHD7/CHD8 chromatin remodeling complex (identified by SILAC-MS, Co-IP, and yeast two-hybrid), and separately has been shown to support vascular endothelial cell proliferation in vitro, but its precise molecular function within the CHD7/CHD8 complex remains uncharacterized."},"narrative":{"mechanistic_narrative":"FAM124B is a predominantly nuclear protein that functions as a component of a CHD7- and CHD8-containing chromatin remodeling complex [PMID:23285124]. It binds directly to the CHD8 subunit and co-immunoprecipitates with the assembled CHD7/CHD8 complex, and it is expressed broadly across embryonic and adult tissues [PMID:23285124]. Beyond this complex association, its precise molecular activity within the chromatin remodeling machinery has not been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing whether FAM124B has any defined molecular context, this work identified it as a direct binding partner of CHD8 and a member of a CHD7/CHD8 chromatin remodeling complex, placing an uncharacterized protein into a defined nuclear assembly.","evidence":"SILAC mass spectrometry, reciprocal co-immunoprecipitation, direct yeast two-hybrid, and immunofluorescence/subcellular fractionation","pmids":["23285124"],"confidence":"Medium","gaps":["The functional contribution of FAM124B to the CHD7/CHD8 complex's remodeling activity is undefined","No catalytic or structural role assigned within the complex","Target loci or chromatin states regulated by the complex via FAM124B are unknown"]},{"year":2024,"claim":"Probing a cellular phenotype for FAM124B, loss-of-function in endothelial cells reduced proliferation, providing the first functional readout tied to the gene.","evidence":"In vitro knockdown/inhibition proliferation assay in HUVECs","pmids":["39384883"],"confidence":"Low","gaps":["Single in vitro knockdown without mechanistic pathway placement","No link established between the endothelial proliferation phenotype and the CHD7/CHD8 complex role","Not independently confirmed"]},{"year":null,"claim":"The molecular function FAM124B performs within the CHD7/CHD8 complex and how this connects to its cellular roles remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No defined biochemical activity for FAM124B","No connection drawn between chromatin complex membership and the endothelial proliferation phenotype"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0]}],"complexes":["CHD7/CHD8 chromatin remodeling complex"],"partners":["CHD8","CHD7"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9H5Z6","full_name":"Protein FAM124B","aliases":[],"length_aa":455,"mass_kda":51.0,"function":"","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9H5Z6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/FAM124B","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/FAM124B","total_profiled":1310},"omim":[{"mim_id":"618403","title":"FAMILY WITH SEQUENCE SIMILARITY 124, MEMBER B; FAM124B","url":"https://www.omim.org/entry/618403"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"placenta","ntpm":8.0}],"url":"https://www.proteinatlas.org/search/FAM124B"},"hgnc":{"alias_symbol":["FLJ22746"],"prev_symbol":[]},"alphafold":{"accession":"Q9H5Z6","domains":[{"cath_id":"3.10.180.10","chopping":"11-53_64-98_113-246","consensus_level":"medium","plddt":89.9485,"start":11,"end":246}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H5Z6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H5Z6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9H5Z6-F1-predicted_aligned_error_v6.png","plddt_mean":63.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FAM124B","jax_strain_url":"https://www.jax.org/strain/search?query=FAM124B"},"sequence":{"accession":"Q9H5Z6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9H5Z6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9H5Z6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9H5Z6"}},"corpus_meta":[{"pmid":"24514567","id":"PMC_24514567","title":"A genome-wide association study of anorexia nervosa.","date":"2014","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/24514567","citation_count":217,"is_preprint":false},{"pmid":"20724461","id":"PMC_20724461","title":"Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.","date":"2010","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/20724461","citation_count":76,"is_preprint":false},{"pmid":"23285124","id":"PMC_23285124","title":"Identification and characterization of FAM124B as a novel component of a CHD7 and CHD8 containing complex.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23285124","citation_count":22,"is_preprint":false},{"pmid":"34433169","id":"PMC_34433169","title":"Analysis of Genetic Alterations Related to DNA Methylation in Testicular Germ Cell Tumors Based on Data Mining.","date":"2021","source":"Cytogenetic and genome research","url":"https://pubmed.ncbi.nlm.nih.gov/34433169","citation_count":4,"is_preprint":false},{"pmid":"39384883","id":"PMC_39384883","title":"Genome-wide association study of subfoveal choroidal thickness in a longitudinal cohort of older adults.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39384883","citation_count":1,"is_preprint":false},{"pmid":"41603298","id":"PMC_41603298","title":"High-throughput single-cell DNA methylation and chromatin accessibility co-profiling with SpliCOOL-seq.","date":"2026","source":"Clinical and translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41603298","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5717,"output_tokens":553,"usd":0.012723,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6891,"output_tokens":1062,"usd":0.030502,"stage2_stop_reason":"end_turn"},"total_usd":0.043225,"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\": 2012,\n      \"finding\": \"FAM124B was identified as a novel component of a CHD7- and CHD8-containing chromatin remodeling complex; direct binding to the CHD8 subunit was demonstrated by yeast two-hybrid, and association with the full CHD7/CHD8 complex was confirmed by co-immunoprecipitation. FAM124B localizes predominantly to the nucleus and is expressed broadly in embryonic and adult mouse tissues.\",\n      \"method\": \"SILAC mass spectrometry, co-immunoprecipitation, direct yeast two-hybrid, immunofluorescence/subcellular fractionation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus direct yeast two-hybrid establishing direct CHD8 binding, multiple orthogonal methods in a single lab study\",\n      \"pmids\": [\"23285124\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Inhibition of FAM124B in human umbilical vein endothelial cells (HUVECs) decreased vascular endothelial cell proliferation, suggesting FAM124B plays a functional role in endothelial cell proliferation.\",\n      \"method\": \"In vitro loss-of-function experiment in HUVECs (proliferation assay)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single in vitro knockdown experiment, single lab, no mechanistic pathway placement beyond proliferation phenotype\",\n      \"pmids\": [\"39384883\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FAM124B is a predominantly nuclear protein that directly binds CHD8 and associates with a CHD7/CHD8 chromatin remodeling complex (identified by SILAC-MS, Co-IP, and yeast two-hybrid), and separately has been shown to support vascular endothelial cell proliferation in vitro, but its precise molecular function within the CHD7/CHD8 complex remains uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FAM124B is a predominantly nuclear protein that functions as a component of a CHD7- and CHD8-containing chromatin remodeling complex [#0]. It binds directly to the CHD8 subunit and co-immunoprecipitates with the assembled CHD7/CHD8 complex, and it is expressed broadly across embryonic and adult tissues [#0]. Beyond this complex association, its precise molecular activity within the chromatin remodeling machinery has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing whether FAM124B has any defined molecular context, this work identified it as a direct binding partner of CHD8 and a member of a CHD7/CHD8 chromatin remodeling complex, placing an uncharacterized protein into a defined nuclear assembly.\",\n      \"evidence\": \"SILAC mass spectrometry, reciprocal co-immunoprecipitation, direct yeast two-hybrid, and immunofluorescence/subcellular fractionation\",\n      \"pmids\": [\"23285124\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The functional contribution of FAM124B to the CHD7/CHD8 complex's remodeling activity is undefined\",\n        \"No catalytic or structural role assigned within the complex\",\n        \"Target loci or chromatin states regulated by the complex via FAM124B are unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Probing a cellular phenotype for FAM124B, loss-of-function in endothelial cells reduced proliferation, providing the first functional readout tied to the gene.\",\n      \"evidence\": \"In vitro knockdown/inhibition proliferation assay in HUVECs\",\n      \"pmids\": [\"39384883\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single in vitro knockdown without mechanistic pathway placement\",\n        \"No link established between the endothelial proliferation phenotype and the CHD7/CHD8 complex role\",\n        \"Not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function FAM124B performs within the CHD7/CHD8 complex and how this connects to its cellular roles remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No defined biochemical activity for FAM124B\",\n        \"No connection drawn between chromatin complex membership and the endothelial proliferation phenotype\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"CHD7/CHD8 chromatin remodeling complex\"],\n    \"partners\": [\"CHD8\", \"CHD7\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":2,"faith_total":2,"faith_pct":100.0}}