{"gene":"BAAT","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2003,"finding":"A BAAT mutation identified in Amish individuals with familial hypercholanemia (FHC) abrogates bile acid-conjugating enzyme activity; serum of individuals homozygous for this mutation contains only unconjugated bile acids, demonstrating that BAAT is required for bile acid amino acid conjugation in vivo.","method":"Human genetic analysis of FHC patients combined with functional enzyme activity assay showing loss of BAAT activity and serum bile acid profiling demonstrating absence of conjugated bile acids in homozygous carriers","journal":"Nature genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct functional enzyme activity assay paired with serum metabolite profiling in human carriers, replicated by the knockout mouse study (PMID:36243101)","pmids":["12704386"],"is_preprint":false},{"year":2003,"finding":"BAAT genotype modifies penetrance of familial hypercholanemia in individuals homozygous for TJP2 mutations, placing BAAT in an oligogenic inheritance context where mutations in both TJP2 and BAAT disrupt bile acid transport and enterohepatic circulation.","method":"Genetic epistasis analysis in Amish FHC pedigrees; double-mutation carriers showed altered phenotypic penetrance compared to single TJP2 mutation carriers","journal":"Nature genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single-lab genetic epistasis in a defined population; pathway placement supported by mechanistic data but oligogenic model not independently replicated","pmids":["12704386"],"is_preprint":false},{"year":2022,"finding":"Baat knockout mice produce a bile acid pool highly enriched in unconjugated cholic acid but retain some glycine-conjugated bile acids at near-wild-type concentrations and show elevated microbially conjugated bile acids, indicating that BAAT is the primary but not sole route of bile acid amino acid conjugation in mice; peroxisomal acyltransferases Acnat1 and Acnat2 (mouse-specific BAAT duplications inactive in humans) likely account for residual conjugation.","method":"Baat-/- mouse knockout with LC-MS bile acid profiling of liver and feces; antibiotic treatment to distinguish microbial vs. host-derived conjugation","journal":"Journal of lipid research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean knockout with orthogonal metabolomic profiling and antibiotic controls in a single lab, multiple complementary readouts establishing enzymatic role","pmids":["36243101"],"is_preprint":false},{"year":2022,"finding":"Baat knockout causes post-natal growth deficits (underweight after weaning with subsequent catch-up growth), increased phospholipid excretion, decreased subcutaneous fat pad mass, decreased liver mass, reduced hepatic glycogen, and reduced hepatic vitamin A stores at three weeks of age, establishing BAAT-mediated bile acid conjugation as important for early post-natal lipid and fat-soluble vitamin absorption.","method":"Baat-/- mouse knockout with body weight monitoring, histological staining (glycogen), tissue mass measurements, and biochemical analysis of fat-soluble vitamin stores","journal":"Journal of lipid research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with specific phenotypic readouts in a single lab; cellular mechanism linking BAAT loss to each phenotype inferred but not directly dissected","pmids":["36243101"],"is_preprint":false},{"year":2022,"finding":"Baat knockout alters the gut microbiome composition in early life, demonstrating that BAAT-dependent bile acid conjugation shapes the intestinal microbial community.","method":"Baat-/- mouse knockout with 16S rRNA-based gut microbiome profiling at multiple developmental time points","journal":"Journal of lipid research","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single method (microbiome sequencing) with KO model; mechanism linking bile acid conjugation to specific microbiome changes not dissected beyond the association","pmids":["36243101"],"is_preprint":false}],"current_model":"BAAT (bile acid-CoA:amino acid N-acyltransferase) is the principal hepatic enzyme that conjugates bile acids with glycine or taurine in the final step of bile acid synthesis; loss-of-function mutations or knockout abolish conjugated bile acid production (leaving only unconjugated bile acids in serum/bile), impair post-natal lipid and fat-soluble vitamin absorption, reshape the gut microbiome in early life, and — in humans — modify the penetrance of familial hypercholanemia in an oligogenic interaction with TJP2."},"narrative":{"mechanistic_narrative":"BAAT is the principal hepatic enzyme that catalyzes the final step of bile acid synthesis, conjugating bile acids to glycine or taurine; loss of BAAT activity in humans homozygous for a BAAT mutation leaves only unconjugated bile acids in serum, establishing that the enzyme is required for bile acid amino acid conjugation in vivo [PMID:12704386]. Baat knockout mice confirm this enzymatic role, producing a bile acid pool dominated by unconjugated cholic acid, although residual host-derived glycine-conjugated and microbially conjugated bile acids persist, indicating BAAT is the primary but not the sole route of conjugation in mice [PMID:36243101]. Through its control of conjugated bile acid production, BAAT supports early post-natal lipid and fat-soluble vitamin absorption — its loss in mice causes post-natal growth deficits, reduced fat pad and liver mass, reduced hepatic glycogen and vitamin A stores, and increased phospholipid excretion [PMID:36243101] — and shapes the composition of the early-life gut microbiome [PMID:36243101]. In humans, BAAT genotype modifies the penetrance of familial hypercholanemia in an oligogenic interaction with TJP2 mutations [PMID:12704386].","teleology":[{"year":2003,"claim":"Established that BAAT is genetically and enzymatically required for bile acid amino acid conjugation in humans, resolving whether the conjugation step depends on this enzyme in vivo.","evidence":"Human genetic analysis of Amish familial hypercholanemia patients with functional enzyme assay and serum bile acid profiling showing only unconjugated bile acids in homozygous carriers","pmids":["12704386"],"confidence":"High","gaps":["Does not resolve the structural or kinetic basis of glycine vs. taurine selectivity","Subcellular site of conjugation not dissected in this study"]},{"year":2003,"claim":"Placed BAAT within an oligogenic disease framework by showing its genotype modifies penetrance of familial hypercholanemia in TJP2-mutant individuals, linking conjugation to enterohepatic transport phenotypes.","evidence":"Genetic epistasis analysis in Amish FHC pedigrees comparing single TJP2 versus double TJP2/BAAT mutation carriers","pmids":["12704386"],"confidence":"Medium","gaps":["Oligogenic model not independently replicated outside this population","Molecular mechanism connecting BAAT loss to altered TJP2-driven transport not defined"]},{"year":2022,"claim":"Defined BAAT as the primary but non-exclusive route of bile acid conjugation, showing residual host and microbial conjugation persists in its absence.","evidence":"Baat-/- mouse with LC-MS bile acid profiling of liver and feces plus antibiotic treatment to separate microbial from host conjugation","pmids":["36243101"],"confidence":"High","gaps":["Identity of the residual host conjugating enzymes (e.g. Acnat1/2) inferred but not directly demonstrated","Human relevance of mouse-specific peroxisomal duplications unaddressed"]},{"year":2022,"claim":"Connected BAAT-dependent conjugation to whole-organism physiology, establishing its importance for early post-natal lipid and fat-soluble vitamin absorption and growth.","evidence":"Baat-/- mouse phenotyping: body weight, tissue mass, glycogen histology, and fat-soluble vitamin store measurements at three weeks","pmids":["36243101"],"confidence":"Medium","gaps":["Cellular mechanism linking conjugation loss to each phenotype not directly dissected","Whether catch-up growth fully normalizes downstream metabolism unknown"]},{"year":2022,"claim":"Extended BAAT function beyond the host by showing its conjugation activity shapes early-life intestinal microbial community composition.","evidence":"16S rRNA gut microbiome profiling of Baat-/- mice at multiple developmental time points","pmids":["36243101"],"confidence":"Medium","gaps":["Mechanism linking specific bile acid species to particular microbial shifts not dissected","Single method (16S sequencing) without functional microbiome validation"]},{"year":null,"claim":"The structural basis of BAAT substrate selectivity (glycine vs. taurine), its subcellular conjugation site, and the human-specific consequences distinguishing it from mouse-specific paralogs remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or kinetic mechanism for amino acid donor selectivity in the corpus","Human enzymes accounting for any residual conjugation not identified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,2]}],"localization":[],"pathway":[{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[0,2,3]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q14032","full_name":"Bile acid-CoA:amino acid N-acyltransferase","aliases":["Bile acid-CoA thioesterase","Choloyl-CoA hydrolase","Glycine N-choloyltransferase","Long-chain fatty-acyl-CoA hydrolase"],"length_aa":418,"mass_kda":46.3,"function":"Catalyzes the amidation of bile acids (BAs) with the amino acids taurine and glycine (PubMed:12239217, PubMed:12810727, PubMed:2037576, PubMed:8034703). More than 95% of the BAs are N-acyl amidates with glycine and taurine (PubMed:8034703). Amidation of BAs in the liver with glycine or taurine prior to their excretion into bile is an important biochemical event in bile acid metabolism (PubMed:12810727). This conjugation (or amidation) plays several important biological roles in that it promotes the secretion of BAs and cholesterol into bile and increases the detergent properties of BAs in the intestine, which facilitates lipid and vitamin absorption (PubMed:12810727). May also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids (PubMed:12239217, PubMed:12810727, PubMed:8034703). In vitro, catalyzes the hydrolysis of long- and very long-chain saturated acyl-CoAs to the free fatty acid and coenzyme A (CoASH), and conjugates glycine to these acyl-CoAs (PubMed:12810727)","subcellular_location":"Cytoplasm, cytosol; Peroxisome","url":"https://www.uniprot.org/uniprotkb/Q14032/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/BAAT","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/BAAT","total_profiled":1310},"omim":[{"mim_id":"619232","title":"HYPERCHOLANEMIA, FAMILIAL 3; FHCA3","url":"https://www.omim.org/entry/619232"},{"mim_id":"611153","title":"XPA, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPA","url":"https://www.omim.org/entry/611153"},{"mim_id":"607748","title":"HYPERCHOLANEMIA, FAMILIAL 1; FHCA1","url":"https://www.omim.org/entry/607748"},{"mim_id":"607709","title":"TIGHT JUNCTION PROTEIN 2; TJP2","url":"https://www.omim.org/entry/607709"},{"mim_id":"602938","title":"BILE ACID CoA:AMINO ACID N-ACYLTRANSFERASE; BAAT","url":"https://www.omim.org/entry/602938"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"liver","ntpm":674.5}],"url":"https://www.proteinatlas.org/search/BAAT"},"hgnc":{"alias_symbol":["BAT","BACAT"],"prev_symbol":[]},"alphafold":{"accession":"Q14032","domains":[{"cath_id":"2.60.40.2240","chopping":"4-132","consensus_level":"high","plddt":96.1543,"start":4,"end":132},{"cath_id":"3.40.50.1820","chopping":"139-411","consensus_level":"high","plddt":95.5648,"start":139,"end":411}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14032","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q14032-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q14032-F1-predicted_aligned_error_v6.png","plddt_mean":95.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=BAAT","jax_strain_url":"https://www.jax.org/strain/search?query=BAAT"},"sequence":{"accession":"Q14032","fasta_url":"https://rest.uniprot.org/uniprotkb/Q14032.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q14032/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q14032"}},"corpus_meta":[{"pmid":"32015507","id":"PMC_32015507","title":"A 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in the Pteropodid bat Eonycteris spelaea.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31941952","citation_count":23,"is_preprint":false},{"pmid":"36243101","id":"PMC_36243101","title":"Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice.","date":"2022","source":"Journal of lipid research","url":"https://pubmed.ncbi.nlm.nih.gov/36243101","citation_count":22,"is_preprint":false},{"pmid":"24809961","id":"PMC_24809961","title":"Genomic landscape of human, bat, and ex vivo DNA transposon integrations.","date":"2014","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/24809961","citation_count":22,"is_preprint":false},{"pmid":"28906230","id":"PMC_28906230","title":"Novel insights into bat influenza A viruses.","date":"2017","source":"The Journal of general 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Regulatory, integrative and comparative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/12010738","citation_count":20,"is_preprint":false},{"pmid":"36378474","id":"PMC_36378474","title":"Global patterns of phylogenetic diversity and transmission of bat coronavirus.","date":"2022","source":"Science China. Life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36378474","citation_count":18,"is_preprint":false},{"pmid":"38963761","id":"PMC_38963761","title":"Lipid-associated macrophages reshape BAT cell identity in obesity.","date":"2024","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/38963761","citation_count":17,"is_preprint":false},{"pmid":"36417954","id":"PMC_36417954","title":"Isolation of Bat Sarbecoviruses, Japan.","date":"2022","source":"Emerging infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/36417954","citation_count":17,"is_preprint":false},{"pmid":"32934084","id":"PMC_32934084","title":"A Potent Postentry Restriction to Primate Lentiviruses in a Yinpterochiropteran Bat.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32934084","citation_count":17,"is_preprint":false},{"pmid":"40399606","id":"PMC_40399606","title":"Bat organoids reveal antiviral responses at epithelial surfaces.","date":"2025","source":"Nature immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40399606","citation_count":16,"is_preprint":false},{"pmid":"34579766","id":"PMC_34579766","title":"Relationship among bats, parasitic bat flies, and associated pathogens in Korea.","date":"2021","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/34579766","citation_count":16,"is_preprint":false},{"pmid":"29492770","id":"PMC_29492770","title":"Assessing bat droppings and predatory bird pellets for vector-borne bacteria: molecular evidence of bat-associated Neorickettsia sp. in Europe.","date":"2018","source":"Antonie van Leeuwenhoek","url":"https://pubmed.ncbi.nlm.nih.gov/29492770","citation_count":16,"is_preprint":false},{"pmid":"34325659","id":"PMC_34325659","title":"Cospeciation of coronavirus and paramyxovirus with their bat hosts in the same geographical areas.","date":"2021","source":"BMC ecology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/34325659","citation_count":15,"is_preprint":false},{"pmid":"9185174","id":"PMC_9185174","title":"Protein kinase C from bat brain: the enzyme from a hibernating mammal.","date":"1997","source":"Neurochemistry international","url":"https://pubmed.ncbi.nlm.nih.gov/9185174","citation_count":15,"is_preprint":false},{"pmid":"35677039","id":"PMC_35677039","title":"Bat Employs a Conserved MDA5 Gene to Trigger Antiviral Innate Immune Responses.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35677039","citation_count":15,"is_preprint":false},{"pmid":"32295912","id":"PMC_32295912","title":"Impact of Měnglà Virus Proteins on Human and Bat Innate Immune Pathways.","date":"2020","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/32295912","citation_count":15,"is_preprint":false},{"pmid":"39833544","id":"PMC_39833544","title":"A compendium of 8,176 bat RNA viral metagenomes reveals ecological drivers and circulation dynamics.","date":"2025","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/39833544","citation_count":14,"is_preprint":false},{"pmid":"37656196","id":"PMC_37656196","title":"Bartonella Infection in Fruit Bats and Bat Flies, Bangladesh.","date":"2023","source":"Microbial ecology","url":"https://pubmed.ncbi.nlm.nih.gov/37656196","citation_count":14,"is_preprint":false},{"pmid":"34387012","id":"PMC_34387012","title":"Taking flight: An ecological, evolutionary and genomic perspective on bat telomeres.","date":"2021","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/34387012","citation_count":14,"is_preprint":false},{"pmid":"34982782","id":"PMC_34982782","title":"Genetic identification of bat species for pathogen surveillance across France.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/34982782","citation_count":14,"is_preprint":false},{"pmid":"36844977","id":"PMC_36844977","title":"High prevalence and genetic diversity of hemoplasmas in bats and bat ectoparasites from China.","date":"2023","source":"One health (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/36844977","citation_count":13,"is_preprint":false},{"pmid":"30999711","id":"PMC_30999711","title":"Discovery and Characterization of Novel Bat Coronavirus Lineages from Kazakhstan.","date":"2019","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/30999711","citation_count":13,"is_preprint":false},{"pmid":"32859395","id":"PMC_32859395","title":"Bat mammalian orthoreoviruses cause severe pneumonia in mice.","date":"2020","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/32859395","citation_count":13,"is_preprint":false},{"pmid":"36467699","id":"PMC_36467699","title":"Temperature modulates systemic and central actions of thyroid hormones on BAT thermogenesis.","date":"2022","source":"Frontiers in physiology","url":"https://pubmed.ncbi.nlm.nih.gov/36467699","citation_count":13,"is_preprint":false},{"pmid":"23097437","id":"PMC_23097437","title":"Deep RNA sequencing reveals complex transcriptional landscape of a bat adenovirus.","date":"2012","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/23097437","citation_count":13,"is_preprint":false},{"pmid":"31871229","id":"PMC_31871229","title":"Bat-Borne Influenza A Viruses: An Awakening.","date":"2021","source":"Cold Spring Harbor perspectives in medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31871229","citation_count":12,"is_preprint":false},{"pmid":"34452389","id":"PMC_34452389","title":"Astrovirus in Reunion Free-Tailed Bat (Mormopterus francoismoutoui).","date":"2021","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/34452389","citation_count":12,"is_preprint":false},{"pmid":"29633182","id":"PMC_29633182","title":"BAT Exosomes: Metabolic Crosstalk with Other Organs and Biomarkers for BAT Activity.","date":"2019","source":"Handbook of experimental pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/29633182","citation_count":12,"is_preprint":false},{"pmid":"39028202","id":"PMC_39028202","title":"Structural determinants of spike infectivity in bat SARS-like coronaviruses RsSHC014 and WIV1.","date":"2024","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/39028202","citation_count":12,"is_preprint":false},{"pmid":"29925396","id":"PMC_29925396","title":"Bat Astrovirus in Mozambique.","date":"2018","source":"Virology journal","url":"https://pubmed.ncbi.nlm.nih.gov/29925396","citation_count":11,"is_preprint":false},{"pmid":"36862584","id":"PMC_36862584","title":"Substantial viral and bacterial diversity at the bat-tick interface.","date":"2023","source":"Microbial genomics","url":"https://pubmed.ncbi.nlm.nih.gov/36862584","citation_count":11,"is_preprint":false},{"pmid":"37142773","id":"PMC_37142773","title":"Metagenomics-enabled reverse-genetics assembly and characterization of myotis bat morbillivirus.","date":"2023","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/37142773","citation_count":11,"is_preprint":false},{"pmid":"36750225","id":"PMC_36750225","title":"Synchronicity of viral shedding in molossid bat maternity colonies.","date":"2023","source":"Epidemiology and infection","url":"https://pubmed.ncbi.nlm.nih.gov/36750225","citation_count":11,"is_preprint":false},{"pmid":"31676302","id":"PMC_31676302","title":"A TRIZ-inspired bat algorithm for gene selection in cancer classification.","date":"2019","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/31676302","citation_count":11,"is_preprint":false},{"pmid":"34687642","id":"PMC_34687642","title":"Trypanosoma cruzi DNA in Desmodus rotundus (common vampire bat) and Histiotus montanus (small big-eared brown bat) from Chile.","date":"2021","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/34687642","citation_count":11,"is_preprint":false},{"pmid":"33143230","id":"PMC_33143230","title":"Achimota Pararubulavirus 3: A New Bat-Derived Paramyxovirus of the Genus Pararubulavirus.","date":"2020","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/33143230","citation_count":11,"is_preprint":false},{"pmid":"31835274","id":"PMC_31835274","title":"Testicular characterization and spermatogenesis of the hematophagous bat Diphylla ecaudata.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31835274","citation_count":10,"is_preprint":false},{"pmid":"29136119","id":"PMC_29136119","title":"The Bat as a New Model of Cortical Development.","date":"2018","source":"Cerebral cortex (New York, N.Y. : 1991)","url":"https://pubmed.ncbi.nlm.nih.gov/29136119","citation_count":10,"is_preprint":false},{"pmid":"34075253","id":"PMC_34075253","title":"[From SARS, MERS to COVID-19: A journey to understand bat coronaviruses].","date":"2021","source":"Bulletin de l'Academie nationale de medecine","url":"https://pubmed.ncbi.nlm.nih.gov/34075253","citation_count":10,"is_preprint":false},{"pmid":"34842304","id":"PMC_34842304","title":"A comprehensive profiling of innate immune responses in Eptesicus bat cells.","date":"2022","source":"Microbiology and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/34842304","citation_count":10,"is_preprint":false},{"pmid":"30718752","id":"PMC_30718752","title":"Generation of bat-derived influenza viruses and their reassortants.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30718752","citation_count":9,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":45737,"output_tokens":1505,"usd":0.079893,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8059,"output_tokens":2013,"usd":0.04531,"stage2_stop_reason":"end_turn"},"total_usd":0.125203,"stage1_batch_id":"msgbatch_0179Z2pxRYBsXi2xADneafRw","stage2_batch_id":"msgbatch_01LaY9ZaVdgjWArcZo9eqQE5","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through all 100 abstracts, I need to identify papers about BAAT (bile acid-CoA:amino acid N-acyltransferase, also known as BAT or BACAT). The vast majority of papers in this corpus are about bats (the animal), bat coronaviruses, bat biology, brown adipose tissue (BAT), or basophil activation testing (BAT) — none of which are the BAAT gene.\n\nOnly two papers are clearly about the BAAT gene:\n\n1. **PMID:12704386** (Carlton et al., 2003) — directly about BAAT mutations in familial hypercholanemia\n2. **PMID:36243101** (Neugebauer et al., 2022) — Baat gene knockout study in mice\n\nLet me extract mechanistic discoveries from these two papers.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"A BAAT mutation identified in Amish individuals with familial hypercholanemia (FHC) abrogates bile acid-conjugating enzyme activity; serum of individuals homozygous for this mutation contains only unconjugated bile acids, demonstrating that BAAT is required for bile acid amino acid conjugation in vivo.\",\n      \"method\": \"Human genetic analysis of FHC patients combined with functional enzyme activity assay showing loss of BAAT activity and serum bile acid profiling demonstrating absence of conjugated bile acids in homozygous carriers\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct functional enzyme activity assay paired with serum metabolite profiling in human carriers, replicated by the knockout mouse study (PMID:36243101)\",\n      \"pmids\": [\"12704386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"BAAT genotype modifies penetrance of familial hypercholanemia in individuals homozygous for TJP2 mutations, placing BAAT in an oligogenic inheritance context where mutations in both TJP2 and BAAT disrupt bile acid transport and enterohepatic circulation.\",\n      \"method\": \"Genetic epistasis analysis in Amish FHC pedigrees; double-mutation carriers showed altered phenotypic penetrance compared to single TJP2 mutation carriers\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single-lab genetic epistasis in a defined population; pathway placement supported by mechanistic data but oligogenic model not independently replicated\",\n      \"pmids\": [\"12704386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Baat knockout mice produce a bile acid pool highly enriched in unconjugated cholic acid but retain some glycine-conjugated bile acids at near-wild-type concentrations and show elevated microbially conjugated bile acids, indicating that BAAT is the primary but not sole route of bile acid amino acid conjugation in mice; peroxisomal acyltransferases Acnat1 and Acnat2 (mouse-specific BAAT duplications inactive in humans) likely account for residual conjugation.\",\n      \"method\": \"Baat-/- mouse knockout with LC-MS bile acid profiling of liver and feces; antibiotic treatment to distinguish microbial vs. host-derived conjugation\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with orthogonal metabolomic profiling and antibiotic controls in a single lab, multiple complementary readouts establishing enzymatic role\",\n      \"pmids\": [\"36243101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Baat knockout causes post-natal growth deficits (underweight after weaning with subsequent catch-up growth), increased phospholipid excretion, decreased subcutaneous fat pad mass, decreased liver mass, reduced hepatic glycogen, and reduced hepatic vitamin A stores at three weeks of age, establishing BAAT-mediated bile acid conjugation as important for early post-natal lipid and fat-soluble vitamin absorption.\",\n      \"method\": \"Baat-/- mouse knockout with body weight monitoring, histological staining (glycogen), tissue mass measurements, and biochemical analysis of fat-soluble vitamin stores\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with specific phenotypic readouts in a single lab; cellular mechanism linking BAAT loss to each phenotype inferred but not directly dissected\",\n      \"pmids\": [\"36243101\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Baat knockout alters the gut microbiome composition in early life, demonstrating that BAAT-dependent bile acid conjugation shapes the intestinal microbial community.\",\n      \"method\": \"Baat-/- mouse knockout with 16S rRNA-based gut microbiome profiling at multiple developmental time points\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (microbiome sequencing) with KO model; mechanism linking bile acid conjugation to specific microbiome changes not dissected beyond the association\",\n      \"pmids\": [\"36243101\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"BAAT (bile acid-CoA:amino acid N-acyltransferase) is the principal hepatic enzyme that conjugates bile acids with glycine or taurine in the final step of bile acid synthesis; loss-of-function mutations or knockout abolish conjugated bile acid production (leaving only unconjugated bile acids in serum/bile), impair post-natal lipid and fat-soluble vitamin absorption, reshape the gut microbiome in early life, and — in humans — modify the penetrance of familial hypercholanemia in an oligogenic interaction with TJP2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BAAT is the principal hepatic enzyme that catalyzes the final step of bile acid synthesis, conjugating bile acids to glycine or taurine; loss of BAAT activity in humans homozygous for a BAAT mutation leaves only unconjugated bile acids in serum, establishing that the enzyme is required for bile acid amino acid conjugation in vivo [#0]. Baat knockout mice confirm this enzymatic role, producing a bile acid pool dominated by unconjugated cholic acid, although residual host-derived glycine-conjugated and microbially conjugated bile acids persist, indicating BAAT is the primary but not the sole route of conjugation in mice [#2]. Through its control of conjugated bile acid production, BAAT supports early post-natal lipid and fat-soluble vitamin absorption \\u2014 its loss in mice causes post-natal growth deficits, reduced fat pad and liver mass, reduced hepatic glycogen and vitamin A stores, and increased phospholipid excretion [#3] \\u2014 and shapes the composition of the early-life gut microbiome [#4]. In humans, BAAT genotype modifies the penetrance of familial hypercholanemia in an oligogenic interaction with TJP2 mutations [#0, #1].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established that BAAT is genetically and enzymatically required for bile acid amino acid conjugation in humans, resolving whether the conjugation step depends on this enzyme in vivo.\",\n      \"evidence\": \"Human genetic analysis of Amish familial hypercholanemia patients with functional enzyme assay and serum bile acid profiling showing only unconjugated bile acids in homozygous carriers\",\n      \"pmids\": [\"12704386\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not resolve the structural or kinetic basis of glycine vs. taurine selectivity\",\n        \"Subcellular site of conjugation not dissected in this study\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Placed BAAT within an oligogenic disease framework by showing its genotype modifies penetrance of familial hypercholanemia in TJP2-mutant individuals, linking conjugation to enterohepatic transport phenotypes.\",\n      \"evidence\": \"Genetic epistasis analysis in Amish FHC pedigrees comparing single TJP2 versus double TJP2/BAAT mutation carriers\",\n      \"pmids\": [\"12704386\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Oligogenic model not independently replicated outside this population\",\n        \"Molecular mechanism connecting BAAT loss to altered TJP2-driven transport not defined\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined BAAT as the primary but non-exclusive route of bile acid conjugation, showing residual host and microbial conjugation persists in its absence.\",\n      \"evidence\": \"Baat-/- mouse with LC-MS bile acid profiling of liver and feces plus antibiotic treatment to separate microbial from host conjugation\",\n      \"pmids\": [\"36243101\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the residual host conjugating enzymes (e.g. Acnat1/2) inferred but not directly demonstrated\",\n        \"Human relevance of mouse-specific peroxisomal duplications unaddressed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected BAAT-dependent conjugation to whole-organism physiology, establishing its importance for early post-natal lipid and fat-soluble vitamin absorption and growth.\",\n      \"evidence\": \"Baat-/- mouse phenotyping: body weight, tissue mass, glycogen histology, and fat-soluble vitamin store measurements at three weeks\",\n      \"pmids\": [\"36243101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cellular mechanism linking conjugation loss to each phenotype not directly dissected\",\n        \"Whether catch-up growth fully normalizes downstream metabolism unknown\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended BAAT function beyond the host by showing its conjugation activity shapes early-life intestinal microbial community composition.\",\n      \"evidence\": \"16S rRNA gut microbiome profiling of Baat-/- mice at multiple developmental time points\",\n      \"pmids\": [\"36243101\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking specific bile acid species to particular microbial shifts not dissected\",\n        \"Single method (16S sequencing) without functional microbiome validation\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of BAAT substrate selectivity (glycine vs. taurine), its subcellular conjugation site, and the human-specific consequences distinguishing it from mouse-specific paralogs remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or kinetic mechanism for amino acid donor selectivity in the corpus\",\n        \"Human enzymes accounting for any residual conjugation not identified\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0016746\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}