{"gene":"BABAM1","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2009,"finding":"NBA1/MERIT40 is a component of the BRCA1 A complex (containing BRCA1/BARD1, Abraxas, RAP80, BRCC36, and BRE), is required for resistance to ionizing radiation, localizes to DNA damage sites, maintains BRE and Abraxas protein abundance, and is required for recruitment of BRCA1 to DNA damage sites. Four members of the BRCA1-A complex possess polyubiquitin chain-binding capability.","method":"Genetic screen, proteomic analysis, protein localization (live imaging/foci), knockdown with phenotypic readout (IR resistance, G2/M checkpoint)","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal proteomic analysis, localization experiments, functional KD phenotypes, replicated across three independent labs in the same year","pmids":["19261749"],"is_preprint":false},{"year":2009,"finding":"MERIT40 directly interacts with BRE/BRCC45 and is assembled into the RAP80/Abraxas-containing BRCA1 complex via this interaction. MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily by maintaining the stability of BRE and the five-subunit complex.","method":"Co-immunoprecipitation, protein stability assays, knockdown with DNA damage foci and checkpoint readouts","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP defining direct interaction, replicated across multiple labs (PMIDs 19261748, 19261749, 19261746)","pmids":["19261748"],"is_preprint":false},{"year":2009,"finding":"MERIT40 is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting. MERIT40 is required for Rap80-associated Lys63-ubiquitin deubiquitinase (BRCC36 DUB) activity, and for G2 checkpoint and viability responses to ionizing radiation.","method":"Co-immunoprecipitation, knockdown, DUB activity assay, IR sensitivity assay, DNA damage foci","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, DUB assay, functional KD), replicated across labs","pmids":["19261746"],"is_preprint":false},{"year":2011,"finding":"NBA1/MERIT40 interacts with BRE through a C-terminal conserved motif of NBA1 and the C-terminal UEV domain of BRE, and this interaction is critical for maintaining the integrity of both the nuclear Abraxas-BRCC36 complex and the cytoplasmic ABRO1-BRCC36 complex. Knockdown of NBA1 decreases protein levels of components in both complexes and impairs BRCA1 recruitment to damage sites.","method":"Co-immunoprecipitation, domain mapping/mutagenesis, knockdown with functional readouts (IR resistance, BRCA1 foci)","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — domain mutagenesis plus functional validation, single lab with multiple orthogonal methods","pmids":["21282113"],"is_preprint":false},{"year":2015,"finding":"MERIT40 is phosphorylated by Akt following doxorubicin-induced DNA damage. This Akt-mediated phosphorylation of MERIT40 facilitates assembly of the BRCA1-A complex in response to DNA damage and contributes to DNA repair and cell survival.","method":"In vitro kinase assay, phospho-specific antibody, co-immunoprecipitation, cell survival assays with PI3K/Akt inhibitors","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — kinase assay and complex assembly readout in single lab, multiple methods but not independently replicated","pmids":["26027929"],"is_preprint":false},{"year":2015,"finding":"MERIT40 is required for ICL (interstrand cross-link) repair: Merit40-null mice show hypersensitivity to ICLs but not whole-body irradiation. MERIT40 is recruited to ICL lesions prior to FANCD2, and Merit40-null cells exhibit delayed ICL unhooking, reduced end resection, and reduced homologous recombination at ICL damage. Merit40 mutation exacerbated ICL-induced chromosome instability with Brca2 deficiency but not with Fancd2 mutation, defining its epistatic relationship within the FA-BRCA network.","method":"Knockout mouse model, ICL sensitivity assays, DNA repair foci (FANCD2, RAD51), chromosomal instability assays, genetic epistasis","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vivo knockout, multiple repair assays, and genetic epistasis in a single rigorous study","pmids":["26338419"],"is_preprint":false},{"year":2015,"finding":"MERIT40 is a core subunit of an Lnk-associated Lys63 deubiquitinating complex that attenuates HSC expansion. Loss of MERIT40 increases HSC pool size, enhances resistance to cytoablative stress, and increases repopulating ability and self-renewal. M40-null HSCs show hypersensitivity to thrombopoietin (Tpo) stimulation, and HSC phenotypes are abrogated on a Tpo receptor (Mpl)-null background.","method":"Knockout mouse model, serial transplantation, Tpo stimulation assays, genetic epistasis (M40 x Mpl double KO)","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo KO with functional HSC assays and genetic epistasis establishing pathway position","pmids":["25636339"],"is_preprint":false},{"year":2018,"finding":"MERIT40 directly binds Tankyrase (PARP family) via a tankyrase-binding consensus motif, and recruits tankyrase to DNA double-strand break sites following X-ray irradiation. Cells expressing a tankyrase-binding-deficient MERIT40 mutant fail to rescue the IR-sensitivity phenotype of MERIT40 knockdown cells.","method":"LC-MS/MS, co-immunoprecipitation, mutagenesis, DNA damage foci, IR sensitivity assay with rescue","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — LC-MS identification, Co-IP, mutagenesis, and functional rescue in single lab","pmids":["30533199"],"is_preprint":false},{"year":2019,"finding":"The RXXPEG motif of MERIT40 mediates direct interaction with the ARC-V domain of Tankyrase1 (TNKS1). Mutation of RXXPEG (R28A) disrupts MERIT40-TNKS1 interaction and causes aberrant spindle assembly and chromosome misalignment, demonstrating a role for MERIT40 in spindle structure/function through TNKS1.","method":"Mutagenesis (R28A), co-immunoprecipitation, mitotic phenotype analysis (spindle assembly, chromosome alignment)","journal":"Cell biology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mutagenesis with functional phenotype, single lab, single study","pmids":["30571846"],"is_preprint":false},{"year":2022,"finding":"BABAM1 phosphorylation at Ser29 is regulated by mTORC2 in glioblastoma cells. Inhibition of mTORC2 reduces pBABAM1(Ser29), decreases DNA repair activity in the nucleus, and promotes apoptosis. mTORC2 also controls γH2AX levels. These findings place BABAM1 as an mTORC2 downstream effector in the DNA damage response.","method":"Quantitative phosphoproteomic analysis, mTORC2 inhibition (pharmacological), phospho-specific readouts (pBABAM1-Ser29, γH2AX), nuclear fractionation, apoptosis assays","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — quantitative phosphoproteomics and functional inhibitor studies, single lab","pmids":["36315652"],"is_preprint":false},{"year":2013,"finding":"MERIT40 forms a dimer in a concentration-independent manner and contains a stable central domain with structural similarity to vWA-like regions. MERIT40 interacts with ABRAXAS (the adaptor molecule of the BRCA1 complex), helping to bridge and stabilize the complex.","method":"Recombinant protein purification, spectroscopic/calorimetric unfolding assays, molecular modeling, limited proteolysis, pulldown/binding assay","journal":"Journal of biomolecular structure & dynamics","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — biophysical characterization with direct binding assay in single lab","pmids":["24125081"],"is_preprint":false},{"year":2014,"finding":"MERIT40 interacts with ABRAXAS in a non-phosphorylation-dependent manner via the BRCA1-BRCT domain region, acting as an adapter molecule that generates a scaffold among complex members to stabilize the BRCA1-A complex.","method":"Recombinant protein purification, direct binding/pulldown assay, spectroscopic characterization","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay with purified recombinant proteins, single lab","pmids":["24667604"],"is_preprint":false},{"year":2023,"finding":"WWOX physically interacts with MERIT40 and inhibits excessive homologous recombination (HR) activity induced by MERIT40 overexpression. WWOX impairs the MERIT40-Tankyrase interaction, preventing the MERIT40-Tankyrase complex from promoting HR at DSBs.","method":"Co-immunoprecipitation (WWOX-MERIT40 interaction), HR reporter assay, overexpression/knockdown with functional readouts","journal":"Cancer gene therapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, HR functional assay, and interaction disruption in single lab","pmids":["37248434"],"is_preprint":false}],"current_model":"BABAM1 (NBA1/MERIT40) is a core structural and functional subunit of the BRCA1-A complex that directly binds BRE/BRCC45 via a C-terminal conserved motif, stabilizes the complex (maintaining BRE and Abraxas protein levels), and is required for RAP80-directed recruitment of BRCA1 to DNA double-strand breaks and for the Lys63-deubiquitinase activity of BRCC36; it also functions in interstrand cross-link repair upstream of FANCD2, attenuates hematopoietic stem cell expansion through a Tpo/Mpl signaling axis, recruits Tankyrase1 to DSBs via its RXXPEG motif to promote spindle assembly and HR, and is phosphorylated by both Akt and mTORC2 (at distinct sites) to facilitate BRCA1-A complex assembly and DNA repair in response to genotoxic stress."},"narrative":{"mechanistic_narrative":"BABAM1 (NBA1/MERIT40) is a core structural subunit of the BRCA1-A complex that organizes ubiquitin-directed DNA double-strand break (DSB) signaling and links it to homologous recombination and the broader DNA damage response [PMID:19261749, PMID:19261746]. It is incorporated into the RAP80/Abraxas/BRCC36/BRE-containing complex through a direct C-terminal interaction with BRE/BRCC45 and through contacts with the adaptor ABRAXAS, where it functions as a scaffolding/bridging element that stabilizes the assembly and maintains the protein abundance of BRE and Abraxas [PMID:19261748, PMID:21282113, PMID:24125081, PMID:24667604]. By preserving complex integrity, BABAM1 is required for RAP80-directed retention of BRCA1 at DSBs, for the Lys63-deubiquitinase activity of BRCC36, and for the G2/M checkpoint and ionizing-radiation resistance [PMID:19261749, PMID:19261746]; the same C-terminal BRE-binding motif also sustains the cytoplasmic ABRO1-BRCC36 complex [PMID:21282113]. Beyond DSB repair, BABAM1 acts upstream of FANCD2 in interstrand cross-link repair, where Merit40-null cells show delayed ICL unhooking, reduced end resection, and reduced recombination [PMID:26338419], and it recruits Tankyrase1 to DSBs via an N-terminal RXXPEG/tankyrase-binding motif to promote homologous recombination and proper mitotic spindle assembly, an activity restrained by WWOX [PMID:30533199, PMID:30571846, PMID:37248434]. Its repair function is tuned by phosphorylation: Akt phosphorylates BABAM1 to promote BRCA1-A complex assembly after genotoxic stress, and mTORC2 controls BABAM1 Ser29 phosphorylation to sustain nuclear DNA repair activity [PMID:26027929, PMID:36315652]. Independently of DSB repair, BABAM1 is a subunit of an Lnk-associated Lys63-deubiquitinating complex that attenuates hematopoietic stem cell expansion through a Tpo/Mpl signaling axis [PMID:25636339].","teleology":[{"year":2009,"claim":"Establishing that an uncharacterized protein is a bona fide BRCA1-A complex subunit answered whether BRCA1 recruitment to damage sites depends on a dedicated stabilizing factor.","evidence":"Genetic screen and reciprocal proteomics with localization and knockdown checkpoint/IR-resistance readouts, replicated across three labs","pmids":["19261749","19261748","19261746"],"confidence":"High","gaps":["Did not resolve which subunit BABAM1 directly contacts","Mechanism by which it maintains BRE/Abraxas abundance not defined"]},{"year":2011,"claim":"Mapping the BABAM1-BRE interface defined the molecular basis for complex stabilization and revealed a role beyond the nuclear complex.","evidence":"Co-IP with domain mapping/mutagenesis tying the NBA1 C-terminal motif to the BRE UEV domain, plus functional IR/BRCA1-foci readouts","pmids":["21282113"],"confidence":"High","gaps":["Functional consequences of disrupting the cytoplasmic ABRO1-BRCC36 complex not separated from nuclear effects"]},{"year":2013,"claim":"Biophysical characterization addressed how BABAM1 acts structurally, showing it dimerizes and presents a vWA-like core that bridges complex members.","evidence":"Recombinant protein purification, unfolding spectroscopy/calorimetry, modeling, and ABRAXAS binding assays","pmids":["24125081","24667604"],"confidence":"Medium","gaps":["No high-resolution structure of the assembled complex","Functional relevance of dimerization in cells untested"]},{"year":2015,"claim":"In vivo knockout work distinguished BABAM1's DSB role from a distinct requirement in interstrand cross-link repair upstream of FANCD2.","evidence":"Merit40-null mice with ICL sensitivity assays, repair foci, and genetic epistasis against Brca2 and Fancd2","pmids":["26338419"],"confidence":"High","gaps":["Molecular mechanism linking the BRCA1-A complex to ICL unhooking not defined","How BABAM1 acts upstream of FANCD2 unclear"]},{"year":2015,"claim":"Hematopoietic studies revealed a DSB-repair-independent role as a subunit of an Lnk-associated K63-DUB complex restraining stem cell expansion.","evidence":"Knockout mice with serial transplantation, Tpo stimulation, and M40 x Mpl epistasis","pmids":["25636339"],"confidence":"High","gaps":["DUB substrates relevant to Tpo/Mpl signaling not identified","Relationship to the BRCA1-A complex in HSCs unresolved"]},{"year":2015,"claim":"Identifying Akt phosphorylation addressed how BABAM1-dependent complex assembly is activated by genotoxic stress.","evidence":"In vitro kinase assay, phospho-specific antibody, Co-IP, and inhibitor-coupled survival assays","pmids":["26027929"],"confidence":"Medium","gaps":["Phosphosite-to-assembly mechanism not structurally defined","Not independently replicated"]},{"year":2018,"claim":"Discovery of a tankyrase-binding motif showed BABAM1 recruits Tankyrase1 to DSBs, extending its function to PARP-family signaling at breaks.","evidence":"LC-MS/MS, Co-IP, mutagenesis, and IR-sensitivity rescue with a binding-deficient mutant","pmids":["30533199"],"confidence":"Medium","gaps":["Downstream consequence of tankyrase recruitment at breaks not fully defined","Single lab"]},{"year":2019,"claim":"Defining the RXXPEG/ARC-V interface linked BABAM1-Tankyrase1 binding to mitotic spindle assembly and chromosome alignment.","evidence":"R28A mutagenesis, Co-IP, and mitotic phenotype analysis","pmids":["30571846"],"confidence":"Medium","gaps":["Spindle role not connected mechanistically to the DSB-repair function","Single study"]},{"year":2022,"claim":"Placing BABAM1 Ser29 phosphorylation under mTORC2 control identified an additional kinase input governing its nuclear repair activity.","evidence":"Quantitative phosphoproteomics with mTORC2 inhibition, nuclear fractionation, and apoptosis/γH2AX readouts in glioblastoma cells","pmids":["36315652"],"confidence":"Medium","gaps":["Direct vs indirect mTORC2 phosphorylation not established","Relationship between Ser29 and the Akt site unresolved"]},{"year":2023,"claim":"Identifying WWOX as a negative regulator showed how excessive BABAM1-Tankyrase-driven recombination is restrained.","evidence":"Co-IP, HR reporter assays, and interaction-disruption experiments","pmids":["37248434"],"confidence":"Medium","gaps":["Structural basis of WWOX interference with the BABAM1-Tankyrase interface unknown","Single lab"]},{"year":null,"claim":"How BABAM1's multiple kinase inputs, tankyrase-dependent functions, and DUB-complex roles are integrated and coordinated across nuclear repair, mitosis, and hematopoiesis remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking Akt and mTORC2 phosphorylation to specific outputs","Substrates of the BABAM1-containing DUB complexes in different tissues unidentified","No high-resolution structure of BABAM1 within an assembled complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,3,10,11]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,10]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,3,9]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[0,2,5]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[8]}],"complexes":["BRCA1-A complex","Abraxas-BRCC36 complex","ABRO1-BRCC36 complex","Lnk-associated K63-deubiquitinating complex"],"partners":["BRE","ABRAXAS","RAP80","BRCC36","BRCA1","TNKS1","WWOX"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NWV8","full_name":"BRISC and BRCA1-A complex member 1","aliases":["Mediator of RAP80 interactions and targeting subunit of 40 kDa","New component of the BRCA1-A complex"],"length_aa":329,"mass_kda":36.6,"function":"Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985)","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/Q9NWV8/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BABAM1","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/BABAM1","total_profiled":1310},"omim":[{"mim_id":"612766","title":"BRISC AND BRCA1 A COMPLEX, MEMBER 1; BABAM1","url":"https://www.omim.org/entry/612766"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear bodies","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/BABAM1"},"hgnc":{"alias_symbol":["FLJ20571","HSPC142","NBA1","MERIT40"],"prev_symbol":["C19orf62"]},"alphafold":{"accession":"Q9NWV8","domains":[{"cath_id":"3.40.50.410","chopping":"98-301","consensus_level":"high","plddt":94.1739,"start":98,"end":301}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NWV8","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NWV8-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NWV8-F1-predicted_aligned_error_v6.png","plddt_mean":78.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BABAM1","jax_strain_url":"https://www.jax.org/strain/search?query=BABAM1"},"sequence":{"accession":"Q9NWV8","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NWV8.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NWV8/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NWV8"}},"corpus_meta":[{"pmid":"19261749","id":"PMC_19261749","title":"NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261749","citation_count":143,"is_preprint":false},{"pmid":"19261748","id":"PMC_19261748","title":"MERIT40 facilitates BRCA1 localization and DNA damage repair.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261748","citation_count":132,"is_preprint":false},{"pmid":"19261746","id":"PMC_19261746","title":"MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.","date":"2009","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/19261746","citation_count":125,"is_preprint":false},{"pmid":"21282113","id":"PMC_21282113","title":"NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21282113","citation_count":62,"is_preprint":false},{"pmid":"26027929","id":"PMC_26027929","title":"MERIT40 Is an Akt Substrate that Promotes Resolution of DNA Damage Induced by Chemotherapy.","date":"2015","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/26027929","citation_count":41,"is_preprint":false},{"pmid":"26338419","id":"PMC_26338419","title":"MERIT40 cooperates with BRCA2 to resolve DNA interstrand cross-links.","date":"2015","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/26338419","citation_count":25,"is_preprint":false},{"pmid":"30533199","id":"PMC_30533199","title":"MERIT40-dependent recruitment of tankyrase to damaged DNA and its implication for cell sensitivity to DNA-damaging anticancer drugs.","date":"2018","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/30533199","citation_count":18,"is_preprint":false},{"pmid":"19572197","id":"PMC_19572197","title":"Mutation screening of the MERIT40 gene encoding a novel BRCA1 and RAP80 interacting protein in breast cancer families.","date":"2009","source":"Breast cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/19572197","citation_count":11,"is_preprint":false},{"pmid":"36315652","id":"PMC_36315652","title":"Phosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells.","date":"2022","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/36315652","citation_count":9,"is_preprint":false},{"pmid":"25636339","id":"PMC_25636339","title":"MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling.","date":"2015","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/25636339","citation_count":8,"is_preprint":false},{"pmid":"24667604","id":"PMC_24667604","title":"Role of MERIT40 in stabilization of BRCA1 complex: a protein-protein interaction study.","date":"2014","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/24667604","citation_count":7,"is_preprint":false},{"pmid":"37248434","id":"PMC_37248434","title":"WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer.","date":"2023","source":"Cancer gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/37248434","citation_count":6,"is_preprint":false},{"pmid":"24125081","id":"PMC_24125081","title":"Structural and functional characterization of the MERIT40 to understand its role in DNA repair.","date":"2013","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/24125081","citation_count":5,"is_preprint":false},{"pmid":"30571846","id":"PMC_30571846","title":"RXXPEG motif of MERIT40 is required to maintain spindle structure and function through its interaction with Tankyrase1.","date":"2019","source":"Cell biology international","url":"https://pubmed.ncbi.nlm.nih.gov/30571846","citation_count":4,"is_preprint":false},{"pmid":"29383164","id":"PMC_29383164","title":"Regulation of macrophage migration in ischemic mouse hearts via an AKT2/NBA1/SPK1 pathway.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29383164","citation_count":1,"is_preprint":false},{"pmid":"21431873","id":"PMC_21431873","title":"Germline mutational analysis of the C19orf62 gene in African-American women with breast cancer.","date":"2011","source":"Breast cancer research and treatment","url":"https://pubmed.ncbi.nlm.nih.gov/21431873","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.10.29.24316388","title":"Isoform-level analyses of 6 cancers uncover extensive genetic risk mechanisms undetected at the gene-level","date":"2024-10-30","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.29.24316388","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9189,"output_tokens":3267,"usd":0.038286,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10788,"output_tokens":3471,"usd":0.070358,"stage2_stop_reason":"end_turn"},"total_usd":0.108644,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"NBA1/MERIT40 is a component of the BRCA1 A complex (containing BRCA1/BARD1, Abraxas, RAP80, BRCC36, and BRE), is required for resistance to ionizing radiation, localizes to DNA damage sites, maintains BRE and Abraxas protein abundance, and is required for recruitment of BRCA1 to DNA damage sites. Four members of the BRCA1-A complex possess polyubiquitin chain-binding capability.\",\n      \"method\": \"Genetic screen, proteomic analysis, protein localization (live imaging/foci), knockdown with phenotypic readout (IR resistance, G2/M checkpoint)\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal proteomic analysis, localization experiments, functional KD phenotypes, replicated across three independent labs in the same year\",\n      \"pmids\": [\"19261749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MERIT40 directly interacts with BRE/BRCC45 and is assembled into the RAP80/Abraxas-containing BRCA1 complex via this interaction. MERIT40 regulates BRCA1 retention at DNA breaks and checkpoint function primarily by maintaining the stability of BRE and the five-subunit complex.\",\n      \"method\": \"Co-immunoprecipitation, protein stability assays, knockdown with DNA damage foci and checkpoint readouts\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP defining direct interaction, replicated across multiple labs (PMIDs 19261748, 19261749, 19261746)\",\n      \"pmids\": [\"19261748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MERIT40 is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting. MERIT40 is required for Rap80-associated Lys63-ubiquitin deubiquitinase (BRCC36 DUB) activity, and for G2 checkpoint and viability responses to ionizing radiation.\",\n      \"method\": \"Co-immunoprecipitation, knockdown, DUB activity assay, IR sensitivity assay, DNA damage foci\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, DUB assay, functional KD), replicated across labs\",\n      \"pmids\": [\"19261746\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"NBA1/MERIT40 interacts with BRE through a C-terminal conserved motif of NBA1 and the C-terminal UEV domain of BRE, and this interaction is critical for maintaining the integrity of both the nuclear Abraxas-BRCC36 complex and the cytoplasmic ABRO1-BRCC36 complex. Knockdown of NBA1 decreases protein levels of components in both complexes and impairs BRCA1 recruitment to damage sites.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping/mutagenesis, knockdown with functional readouts (IR resistance, BRCA1 foci)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — domain mutagenesis plus functional validation, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"21282113\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 is phosphorylated by Akt following doxorubicin-induced DNA damage. This Akt-mediated phosphorylation of MERIT40 facilitates assembly of the BRCA1-A complex in response to DNA damage and contributes to DNA repair and cell survival.\",\n      \"method\": \"In vitro kinase assay, phospho-specific antibody, co-immunoprecipitation, cell survival assays with PI3K/Akt inhibitors\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — kinase assay and complex assembly readout in single lab, multiple methods but not independently replicated\",\n      \"pmids\": [\"26027929\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 is required for ICL (interstrand cross-link) repair: Merit40-null mice show hypersensitivity to ICLs but not whole-body irradiation. MERIT40 is recruited to ICL lesions prior to FANCD2, and Merit40-null cells exhibit delayed ICL unhooking, reduced end resection, and reduced homologous recombination at ICL damage. Merit40 mutation exacerbated ICL-induced chromosome instability with Brca2 deficiency but not with Fancd2 mutation, defining its epistatic relationship within the FA-BRCA network.\",\n      \"method\": \"Knockout mouse model, ICL sensitivity assays, DNA repair foci (FANCD2, RAD51), chromosomal instability assays, genetic epistasis\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vivo knockout, multiple repair assays, and genetic epistasis in a single rigorous study\",\n      \"pmids\": [\"26338419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MERIT40 is a core subunit of an Lnk-associated Lys63 deubiquitinating complex that attenuates HSC expansion. Loss of MERIT40 increases HSC pool size, enhances resistance to cytoablative stress, and increases repopulating ability and self-renewal. M40-null HSCs show hypersensitivity to thrombopoietin (Tpo) stimulation, and HSC phenotypes are abrogated on a Tpo receptor (Mpl)-null background.\",\n      \"method\": \"Knockout mouse model, serial transplantation, Tpo stimulation assays, genetic epistasis (M40 x Mpl double KO)\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo KO with functional HSC assays and genetic epistasis establishing pathway position\",\n      \"pmids\": [\"25636339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MERIT40 directly binds Tankyrase (PARP family) via a tankyrase-binding consensus motif, and recruits tankyrase to DNA double-strand break sites following X-ray irradiation. Cells expressing a tankyrase-binding-deficient MERIT40 mutant fail to rescue the IR-sensitivity phenotype of MERIT40 knockdown cells.\",\n      \"method\": \"LC-MS/MS, co-immunoprecipitation, mutagenesis, DNA damage foci, IR sensitivity assay with rescue\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — LC-MS identification, Co-IP, mutagenesis, and functional rescue in single lab\",\n      \"pmids\": [\"30533199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The RXXPEG motif of MERIT40 mediates direct interaction with the ARC-V domain of Tankyrase1 (TNKS1). Mutation of RXXPEG (R28A) disrupts MERIT40-TNKS1 interaction and causes aberrant spindle assembly and chromosome misalignment, demonstrating a role for MERIT40 in spindle structure/function through TNKS1.\",\n      \"method\": \"Mutagenesis (R28A), co-immunoprecipitation, mitotic phenotype analysis (spindle assembly, chromosome alignment)\",\n      \"journal\": \"Cell biology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mutagenesis with functional phenotype, single lab, single study\",\n      \"pmids\": [\"30571846\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"BABAM1 phosphorylation at Ser29 is regulated by mTORC2 in glioblastoma cells. Inhibition of mTORC2 reduces pBABAM1(Ser29), decreases DNA repair activity in the nucleus, and promotes apoptosis. mTORC2 also controls γH2AX levels. These findings place BABAM1 as an mTORC2 downstream effector in the DNA damage response.\",\n      \"method\": \"Quantitative phosphoproteomic analysis, mTORC2 inhibition (pharmacological), phospho-specific readouts (pBABAM1-Ser29, γH2AX), nuclear fractionation, apoptosis assays\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — quantitative phosphoproteomics and functional inhibitor studies, single lab\",\n      \"pmids\": [\"36315652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MERIT40 forms a dimer in a concentration-independent manner and contains a stable central domain with structural similarity to vWA-like regions. MERIT40 interacts with ABRAXAS (the adaptor molecule of the BRCA1 complex), helping to bridge and stabilize the complex.\",\n      \"method\": \"Recombinant protein purification, spectroscopic/calorimetric unfolding assays, molecular modeling, limited proteolysis, pulldown/binding assay\",\n      \"journal\": \"Journal of biomolecular structure & dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — biophysical characterization with direct binding assay in single lab\",\n      \"pmids\": [\"24125081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"MERIT40 interacts with ABRAXAS in a non-phosphorylation-dependent manner via the BRCA1-BRCT domain region, acting as an adapter molecule that generates a scaffold among complex members to stabilize the BRCA1-A complex.\",\n      \"method\": \"Recombinant protein purification, direct binding/pulldown assay, spectroscopic characterization\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay with purified recombinant proteins, single lab\",\n      \"pmids\": [\"24667604\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"WWOX physically interacts with MERIT40 and inhibits excessive homologous recombination (HR) activity induced by MERIT40 overexpression. WWOX impairs the MERIT40-Tankyrase interaction, preventing the MERIT40-Tankyrase complex from promoting HR at DSBs.\",\n      \"method\": \"Co-immunoprecipitation (WWOX-MERIT40 interaction), HR reporter assay, overexpression/knockdown with functional readouts\",\n      \"journal\": \"Cancer gene therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, HR functional assay, and interaction disruption in single lab\",\n      \"pmids\": [\"37248434\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BABAM1 (NBA1/MERIT40) is a core structural and functional subunit of the BRCA1-A complex that directly binds BRE/BRCC45 via a C-terminal conserved motif, stabilizes the complex (maintaining BRE and Abraxas protein levels), and is required for RAP80-directed recruitment of BRCA1 to DNA double-strand breaks and for the Lys63-deubiquitinase activity of BRCC36; it also functions in interstrand cross-link repair upstream of FANCD2, attenuates hematopoietic stem cell expansion through a Tpo/Mpl signaling axis, recruits Tankyrase1 to DSBs via its RXXPEG motif to promote spindle assembly and HR, and is phosphorylated by both Akt and mTORC2 (at distinct sites) to facilitate BRCA1-A complex assembly and DNA repair in response to genotoxic stress.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BABAM1 (NBA1/MERIT40) is a core structural subunit of the BRCA1-A complex that organizes ubiquitin-directed DNA double-strand break (DSB) signaling and links it to homologous recombination and the broader DNA damage response [#0, #2]. It is incorporated into the RAP80/Abraxas/BRCC36/BRE-containing complex through a direct C-terminal interaction with BRE/BRCC45 and through contacts with the adaptor ABRAXAS, where it functions as a scaffolding/bridging element that stabilizes the assembly and maintains the protein abundance of BRE and Abraxas [#1, #3, #10, #11]. By preserving complex integrity, BABAM1 is required for RAP80-directed retention of BRCA1 at DSBs, for the Lys63-deubiquitinase activity of BRCC36, and for the G2/M checkpoint and ionizing-radiation resistance [#0, #2]; the same C-terminal BRE-binding motif also sustains the cytoplasmic ABRO1-BRCC36 complex [#3]. Beyond DSB repair, BABAM1 acts upstream of FANCD2 in interstrand cross-link repair, where Merit40-null cells show delayed ICL unhooking, reduced end resection, and reduced recombination [#5], and it recruits Tankyrase1 to DSBs via an N-terminal RXXPEG/tankyrase-binding motif to promote homologous recombination and proper mitotic spindle assembly, an activity restrained by WWOX [#7, #8, #12]. Its repair function is tuned by phosphorylation: Akt phosphorylates BABAM1 to promote BRCA1-A complex assembly after genotoxic stress, and mTORC2 controls BABAM1 Ser29 phosphorylation to sustain nuclear DNA repair activity [#4, #9]. Independently of DSB repair, BABAM1 is a subunit of an Lnk-associated Lys63-deubiquitinating complex that attenuates hematopoietic stem cell expansion through a Tpo/Mpl signaling axis [#6].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing that an uncharacterized protein is a bona fide BRCA1-A complex subunit answered whether BRCA1 recruitment to damage sites depends on a dedicated stabilizing factor.\",\n      \"evidence\": \"Genetic screen and reciprocal proteomics with localization and knockdown checkpoint/IR-resistance readouts, replicated across three labs\",\n      \"pmids\": [\"19261749\", \"19261748\", \"19261746\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which subunit BABAM1 directly contacts\", \"Mechanism by which it maintains BRE/Abraxas abundance not defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Mapping the BABAM1-BRE interface defined the molecular basis for complex stabilization and revealed a role beyond the nuclear complex.\",\n      \"evidence\": \"Co-IP with domain mapping/mutagenesis tying the NBA1 C-terminal motif to the BRE UEV domain, plus functional IR/BRCA1-foci readouts\",\n      \"pmids\": [\"21282113\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequences of disrupting the cytoplasmic ABRO1-BRCC36 complex not separated from nuclear effects\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Biophysical characterization addressed how BABAM1 acts structurally, showing it dimerizes and presents a vWA-like core that bridges complex members.\",\n      \"evidence\": \"Recombinant protein purification, unfolding spectroscopy/calorimetry, modeling, and ABRAXAS binding assays\",\n      \"pmids\": [\"24125081\", \"24667604\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of the assembled complex\", \"Functional relevance of dimerization in cells untested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"In vivo knockout work distinguished BABAM1's DSB role from a distinct requirement in interstrand cross-link repair upstream of FANCD2.\",\n      \"evidence\": \"Merit40-null mice with ICL sensitivity assays, repair foci, and genetic epistasis against Brca2 and Fancd2\",\n      \"pmids\": [\"26338419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism linking the BRCA1-A complex to ICL unhooking not defined\", \"How BABAM1 acts upstream of FANCD2 unclear\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Hematopoietic studies revealed a DSB-repair-independent role as a subunit of an Lnk-associated K63-DUB complex restraining stem cell expansion.\",\n      \"evidence\": \"Knockout mice with serial transplantation, Tpo stimulation, and M40 x Mpl epistasis\",\n      \"pmids\": [\"25636339\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"DUB substrates relevant to Tpo/Mpl signaling not identified\", \"Relationship to the BRCA1-A complex in HSCs unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Identifying Akt phosphorylation addressed how BABAM1-dependent complex assembly is activated by genotoxic stress.\",\n      \"evidence\": \"In vitro kinase assay, phospho-specific antibody, Co-IP, and inhibitor-coupled survival assays\",\n      \"pmids\": [\"26027929\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phosphosite-to-assembly mechanism not structurally defined\", \"Not independently replicated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Discovery of a tankyrase-binding motif showed BABAM1 recruits Tankyrase1 to DSBs, extending its function to PARP-family signaling at breaks.\",\n      \"evidence\": \"LC-MS/MS, Co-IP, mutagenesis, and IR-sensitivity rescue with a binding-deficient mutant\",\n      \"pmids\": [\"30533199\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream consequence of tankyrase recruitment at breaks not fully defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defining the RXXPEG/ARC-V interface linked BABAM1-Tankyrase1 binding to mitotic spindle assembly and chromosome alignment.\",\n      \"evidence\": \"R28A mutagenesis, Co-IP, and mitotic phenotype analysis\",\n      \"pmids\": [\"30571846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Spindle role not connected mechanistically to the DSB-repair function\", \"Single study\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Placing BABAM1 Ser29 phosphorylation under mTORC2 control identified an additional kinase input governing its nuclear repair activity.\",\n      \"evidence\": \"Quantitative phosphoproteomics with mTORC2 inhibition, nuclear fractionation, and apoptosis/\\u03b3H2AX readouts in glioblastoma cells\",\n      \"pmids\": [\"36315652\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect mTORC2 phosphorylation not established\", \"Relationship between Ser29 and the Akt site unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying WWOX as a negative regulator showed how excessive BABAM1-Tankyrase-driven recombination is restrained.\",\n      \"evidence\": \"Co-IP, HR reporter assays, and interaction-disruption experiments\",\n      \"pmids\": [\"37248434\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of WWOX interference with the BABAM1-Tankyrase interface unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How BABAM1's multiple kinase inputs, tankyrase-dependent functions, and DUB-complex roles are integrated and coordinated across nuclear repair, mitosis, and hematopoiesis remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking Akt and mTORC2 phosphorylation to specific outputs\", \"Substrates of the BABAM1-containing DUB complexes in different tissues unidentified\", \"No high-resolution structure of BABAM1 within an assembled complex\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 3, 10, 11]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 3, 9]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [0, 2, 5]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [\n      \"BRCA1-A complex\",\n      \"Abraxas-BRCC36 complex\",\n      \"ABRO1-BRCC36 complex\",\n      \"Lnk-associated K63-deubiquitinating complex\"\n    ],\n    \"partners\": [\n      \"BRE\",\n      \"ABRAXAS\",\n      \"RAP80\",\n      \"BRCC36\",\n      \"BRCA1\",\n      \"TNKS1\",\n      \"WWOX\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}