{"gene":"B4GALT1","run_date":"2026-06-09T22:02:44","timeline":{"discoveries":[{"year":2019,"finding":"B4GALT1 and ST6GAL1 interact via highly charged noncatalytic surfaces (leaving active sites exposed), forming heteromers in the Golgi that are required for their full catalytic activity in sequential N-glycan modification. B4GALT1 uses its active-site surface for homomeric assembly, which silences its catalytic activity, whereas ST6GAL1 uses the same noncatalytic surface for both homomers and heteromers.","method":"Molecular docking simulations, mutagenesis screens, high-throughput FRET analyses in live cells, structural modeling","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (docking, mutagenesis, FRET in live cells) in a single rigorous study establishing interaction surfaces and catalytic consequences","pmids":["31395657"],"is_preprint":false},{"year":2018,"finding":"Wild-type human B4GALT1 exists as a homodimer in dynamic equilibrium with monomer; crystal structures revealed B4GALT1 in both open and closed conformations of the Trp loop and lid regions responsible for donor and acceptor substrate binding. Targeted mutagenesis of key catalytic amino acids impaired homomer formation in vivo, linking catalytic residues to dimer assembly.","method":"X-ray crystallography (crystal structure of wild-type homodimer), targeted mutagenesis, FRET assays in live cells","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutagenesis plus FRET functional validation in a single study","pmids":["30352055"],"is_preprint":false},{"year":2021,"finding":"A missense variant p.Asn352Ser in the functional domain of B4GALT1 reduces galactosyltransferase activity by ~50% compared to wild-type. Carriers show decreased galactosylation and sialylation of ApoB100, fibrinogen, IgG, and transferrin in serum, and B4galt1 353Ser knock-in mice show decreases in LDL-C and fibrinogen, establishing B4GALT1 galactosyltransferase activity as a regulator of lipoprotein and coagulation factor metabolism.","method":"In vitro galactosyltransferase activity assay with mutant vs. wild-type protein, N-linked glycan profiling of human serum, knock-in mouse model","journal":"Science (New York, N.Y.)","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro enzyme assay with mutagenesis, human glycan profiling, and knock-in mouse model providing multiple orthogonal lines of evidence","pmids":["34855475"],"is_preprint":false},{"year":2023,"finding":"B4GALT1 directly mediates N-linked glycosylation of PD-L1 protein, preventing its proteasomal degradation (posttranscriptional stabilization). Additionally, B4GALT1 stabilizes TAZ protein via glycosylation, which in turn activates CD274 (PD-L1) transcription, thereby promoting immune escape in lung adenocarcinoma.","method":"In vitro and in vivo functional/mechanistic experiments including glycosylation assays, protein stability assays, transcriptional reporter assays, loss-of-function studies","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — mechanistic follow-up with multiple in vitro and in vivo approaches; abstract does not specify full reconstitution or structural validation","pmids":["37303063"],"is_preprint":false},{"year":2020,"finding":"B4GALT1 interacts with and stabilizes CDK11p110 via N-linked glycosylation, downstream of p65 transcriptional upregulation of B4GALT1, forming a p65-B4GALT1-CDK11p110 signaling axis that promotes chemoresistance in pancreatic ductal adenocarcinoma.","method":"Co-immunoprecipitation, glycosylation assays, genetic perturbation of B4GALT1 in cell lines, orthotopic PDAC mouse model","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP and glycosylation assays plus in vivo model in a single lab; mechanistic interaction established but full reconstitution not described","pmids":["33309857"],"is_preprint":false},{"year":2023,"finding":"B4GALT1 modifies the N-glycans of integrin α6 and integrin β1, and its loss increases laminin-binding activity of these integrins, promoting HCC cell migration and invasion. Integrins α6 and β1 were identified as main protein substrates of B4GALT1 by mass spectrometry and GSL-II lectin pull-down.","method":"Mass spectrometry-based substrate identification, Griffonia simplicifolia lectin II (GSL-II) pull-down, B4GALT1 knockdown/knockout, integrin-blocking antibody rescue experiments, in vivo lung metastasis model","journal":"Oncogenesis","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (MS substrate ID, lectin pull-down, KO/KD, antibody rescue, in vivo) establishing B4GALT1 as the N-glycosylating enzyme for integrin α6/β1","pmids":["37907465"],"is_preprint":false},{"year":2019,"finding":"In B4GALT1-CDG patients, cholesteryl ester transfer protein (CETP) is hypoglycosylated (specifically hypogalactosylated) and exhibits reduced enzymatic activity, resulting in large HDL particles and altered lipoprotein homeostasis, directly linking B4GALT1-mediated galactosylation to CETP function.","method":"Isoelectric focusing, western blot of CETP glyco-isoforms, CETP activity assay in patient plasma vs. controls","journal":"Journal of inherited metabolic disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical activity assay and glycoform analysis in human patients; single study but uses orthogonal methods","pmids":["31800099"],"is_preprint":false},{"year":2025,"finding":"B4GALT1 interacts with LRP5/6 in the Golgi, causing their retention and reducing LRP5/6 surface translocation, thereby attenuating WNT/β-catenin signaling. B4GALT1 also binds Wntless; Wnt secretion occupying Wntless antagonizes B4GALT1-mediated LRP5/6 retention. Pharmacological uncoupling of Wnt/Wntless with LGK974 enhances LRP5/6 Golgi retention.","method":"Co-immunoprecipitation, cell surface translocation assays, pharmacological inhibition (LGK974), loss-of-function studies","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP and functional cell-based assays in a single study; mechanistic interaction with LRP5/6 and Wntless established","pmids":["41182165"],"is_preprint":false},{"year":2026,"finding":"B4GALT1 directly interacts with IL-1R1 and promotes its N-linked glycosylation specifically at the N193 site, thereby enhancing IL-1R1 protein stability and downstream inflammatory signaling in chondrocytes. AAV-mediated knockdown of B4GALT1 in vivo reduced IL-1R1 protein levels and attenuated cartilage degeneration.","method":"Co-immunoprecipitation, PNGase F treatment, site-directed mutagenesis (N193 site), AAV-mediated in vivo knockdown, DMM mouse OA model","journal":"Cellular signalling","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — Co-IP, site-directed mutagenesis of glycosylation site, PNGase F, and in vivo AAV knockdown providing multiple orthogonal methods in a single study","pmids":["42002123"],"is_preprint":false},{"year":2026,"finding":"B4GALT1-mediated N-glycosylation of PPARγ destabilizes PPARγ protein; B4GALT1 deficiency impairs PPARγ N-glycosylation, leading to PPARγ stabilization, which transcriptionally represses ACSL4, thereby reducing lipid peroxidation and ferroptosis in hepatocytes during MASLD progression.","method":"Hepatocyte-specific B4galt1-knockout mice (CDAHFD model), N-glycosylation assays, gene expression analysis, PPARγ overexpression rescue experiment","journal":"Hepatology communications","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — conditional knockout mouse model plus glycosylation and rescue experiments; single lab, abstract does not detail reconstitution","pmids":["41860570"],"is_preprint":false},{"year":2025,"finding":"Knockout of GALE (UDP-galactose 4'-epimerase), which reduces intracellular UDP-Gal levels, diminishes the ability of the UDP-Gal transporter SLC35A2 to form homomers and to interact with B4GALT1 in the Golgi, indicating that nucleotide sugar availability regulates B4GALT1-SLC35A2 complex formation.","method":"CRISPR/Cas9 knockout of GALE and GALT in HEK293T cells, NanoBiT protein-protein interaction assay, N-glycan profiling","journal":"Frontiers in molecular biosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO with NanoBiT PPI assay and glycan profiling; single lab, two orthogonal methods","pmids":["40230451"],"is_preprint":false},{"year":2012,"finding":"B4GALT1 knockdown in K562/ADR leukemia cells downregulated the Hedgehog signaling pathway and reversed multidrug resistance in vitro and in vivo, identifying a functional link between B4GALT1-mediated galactosylation and Hedgehog pathway activity in chemoresistance.","method":"RNA interference knockdown, enzyme activity assays, lectin blotting, in vitro drug sensitivity assays, in vivo tumor models","journal":"IUBMB life","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RNAi knockdown with enzyme activity assays, lectin blotting, and in vivo validation; single lab","pmids":["23024026"],"is_preprint":false},{"year":2016,"finding":"SOCS3 upregulates miR-124-3p, which targets B4GALT1 mRNA, forming a SOCS3/miR-124-3p/B4GALT1 axis that regulates growth and chemosensitivity of CML cells. Luciferase reporter assay confirmed B4GALT1 as a direct target of miR-124-3p.","method":"Luciferase reporter assay, qPCR, western blotting, CCK-8 assay, tumorigenicity assays in nude mice","journal":"Journal of hematology & oncology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — luciferase reporter validation of miR-124-3p targeting B4GALT1, with in vitro and in vivo functional assays; single lab","pmids":["27516205"],"is_preprint":false},{"year":2016,"finding":"ZFX transcription factor positively regulates B4GALT1 expression in leukemic cells; ZFX silencing decreases B4GALT1 expression and glycoprotein galactosylation. Overexpression of B4GALT1 restored growth and drug resistance in ZFX-silenced cells, placing B4GALT1 downstream of ZFX.","method":"RNAi silencing of ZFX, gene expression analysis, lectin blot assay for galactosylation, B4GALT1 overexpression rescue","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — RNAi + overexpression rescue + lectin blotting in a single lab study","pmids":["27797721"],"is_preprint":false},{"year":2020,"finding":"AKR1C3 interacts with AR-V7 protein in CRPC cells, and this complex represses B4GALT1 expression; B4GALT1 is identified as a tumor suppressor gene in prostate cancer downstream of this complex. The AKR1C3/AR-V7 complex also reciprocally inhibits each other's protein degradation.","method":"Co-immunoprecipitation (AKR1C3/AR-V7 interaction), gene expression analysis, in vitro and in vivo tumor growth assays","journal":"Journal of cellular and molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP for AKR1C3/AR-V7 interaction, with B4GALT1 identified as downstream target via expression analysis; single lab","pmids":["32902124"],"is_preprint":false},{"year":2025,"finding":"NOLC1 acts as a transcription factor to activate B4GALT1 transcriptional expression; SPOP (E3 ubiquitin ligase adaptor) mediates ubiquitination and degradation of NOLC1. ECa-associated SPOP mutants abrogate NOLC1 ubiquitination, leading to NOLC1 accumulation and B4GALT1 upregulation, causing abnormal glycosylation and paclitaxel resistance.","method":"Co-IP for SPOP-NOLC1 interaction, ubiquitination assays, transcriptional reporter assays, B4GALT1 knockdown rescue, in vitro and in vivo functional assays","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP, ubiquitination assay, and transcriptional reporter with rescue experiments; single lab","pmids":["40097806"],"is_preprint":false},{"year":2024,"finding":"Galectin-8 interacts with the type II TGF-β receptor and competes with TGF-β binding, suppressing TGF-β-driven EMT and CRC metastasis. The anti-migratory effect of galectin-8 depends on B4GALT1, which modifies N-glycans on TGF-β receptor, establishing B4GALT1 as required for galectin-8 ligand recognition at the TGF-β receptor.","method":"Co-immunoprecipitation (galectin-8/TGF-βRII), B4GALT1 depletion experiments, migration assays, intra-splenic injection tumor model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP and B4GALT1 depletion functional assays plus in vivo model; single lab","pmids":["39231945"],"is_preprint":false},{"year":2025,"finding":"B4GALT1 galactosylates TCR and CD8 co-receptor components on the CD8+ T-cell surface, and this galactosylation reduces the interaction between TCR and CD8 that is essential for TCR activation. B4GALT1 inactivation enhances TCR-T cell functions but has no effect on CAR-T cells. Substrates were systematically identified by affinity purification and mass spectrometry.","method":"CRISPR/Cas9 genome-wide and custom screens, affinity purification-mass spectrometry for substrate identification, TCR-CD8 fusion protein rescue, syngeneic mouse tumor model","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR screens, AP-MS substrate identification, and genetic rescue; preprint, single lab","pmids":[],"is_preprint":true},{"year":2025,"finding":"B4GALT1 catalyzes galactose elongation of O-glucose glycans specifically on NOTCH1 EGF10 (and NOTCH3 EGF9), forming a 3'-sialyllactose-like structure in cooperation with ST3GAL4. This site-specific elongation significantly impacts NOTCH1 ligand binding and signal transduction. Mutagenesis identified the amino acid at position -2 of the fourth cysteine as critical for galactose elongation.","method":"Mass spectrometry for modification identification, site-directed mutagenesis, ligand-binding assays, Notch signaling reporter assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — MS identification, mutagenesis, and functional Notch signaling assays; preprint, single lab","pmids":[],"is_preprint":true},{"year":2023,"finding":"UBE2Q1 (an E2 ubiquitin-conjugating enzyme) can interact with B4GALT1 protein as demonstrated by co-immunoprecipitation in colorectal cancer cells overexpressing UBE2Q1, and molecular docking confirmed high-affinity interaction between the UBC domain of UBE2Q1 and B4GALT1.","method":"Co-immunoprecipitation (IP/silver staining), molecular docking (MOE software)","journal":"Protein and peptide letters","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP without reciprocal confirmation, supported only by computational docking; single lab, single method","pmids":["37198983"],"is_preprint":false},{"year":2020,"finding":"In bone marrow stromal cells, B4GALT1 expression is positively regulated by the upstream transcription factor c-Jun (via JNK/c-Jun pathway), validated by dual luciferase reporter assay. Overexpression of B4GALT1 in stromal cells promoted proliferation of co-cultured AML cells.","method":"Dual luciferase reporter assay, JNK/c-Jun inhibitor treatment, co-culture proliferation assay by flow cytometry","journal":"Zhongguo shi yan xue ye xue za zhi","confidence":"Low","confidence_rationale":"Tier 3 / Weak — luciferase reporter for upstream regulation; single lab, limited mechanistic follow-up","pmids":["32027290"],"is_preprint":false},{"year":2021,"finding":"In myeloproliferative neoplasm megakaryocytes, increased B4GALT1 expression leads to elevated LacNAc (β4-N-acetyllactosamine/Galβ1,4GlcNAc) expression on platelets, which promotes hepatic thrombopoietin (TPO) synthesis independently of platelet mass, linking B4GALT1-mediated galactosylation to TPO regulation.","method":"B4GALT1 gene expression analysis in patient megakaryocytes, LacNAc expression assays on platelets, JAK1/2 inhibitor treatment experiments","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — patient-derived megakaryocytes with LacNAc functional assays and pharmacological inhibition; single lab","pmids":["33238000"],"is_preprint":false}],"current_model":"B4GALT1 is a Golgi-resident β-1,4-galactosyltransferase that assembles into catalytically regulated homodimers (active-site surfaces mediate silencing homomer) and functional heteromers with ST6GAL1 (via noncatalytic charged surfaces) to sequentially galactosylate N-glycans; it directly N-glycosylates specific substrates including PD-L1, TAZ, CDK11p110, integrin α6/β1, IL-1R1, PPARγ, TCR/CD8 components, and LRP5/6, thereby regulating their stability, ligand binding, or trafficking, and its galactosyltransferase activity (reducible by the p.Asn352Ser variant) controls lipoprotein metabolism, coagulation factor function, and immune signaling."},"narrative":{"mechanistic_narrative":"B4GALT1 is a Golgi-resident β-1,4-galactosyltransferase that adds galactose to N-glycans and whose activity is subject to assembly-level control: wild-type enzyme exists in monomer–homodimer equilibrium, with catalytic-residue surfaces mediating a silencing homomer, while interaction with ST6GAL1 through noncatalytic charged surfaces forms heteromers required for full sequential N-glycan modification [PMID:31395657, PMID:30352055]. Complex formation with the UDP-galactose transporter SLC35A2 is gated by nucleotide-sugar availability, coupling enzyme output to substrate supply [PMID:40230451]. A p.Asn352Ser variant lowers galactosyltransferase activity by ~50%, reducing galactosylation of ApoB100, fibrinogen, IgG, and transferrin and lowering LDL-C and fibrinogen in knock-in mice, establishing B4GALT1 as a regulator of lipoprotein and coagulation factor metabolism [PMID:34855475]; consistent with this, loss of B4GALT1-dependent galactosylation hypoglycosylates and inactivates CETP, altering HDL homeostasis [PMID:31800099]. Beyond bulk glycoprotein processing, B4GALT1 site-specifically glycosylates defined substrates to control their stability, ligand binding, or trafficking: it N-glycosylates and stabilizes PD-L1, TAZ, CDK11p110, and IL-1R1 (at N193), destabilizes PPARγ, modifies integrin α6/β1 to restrain laminin binding, and modifies the TGF-β receptor as required for galectin-8 recognition [PMID:37303063, PMID:33309857, PMID:42002123, PMID:41860570, PMID:37907465, PMID:39231945]. Independent of catalysis, B4GALT1 binds LRP5/6 in the Golgi and retains them intracellularly to attenuate WNT/β-catenin signaling, a retention antagonized by Wntless engagement [PMID:41182165]. Through these substrate-specific actions B4GALT1 influences immune escape, inflammatory and ferroptotic signaling, integrin-driven migration, and chemoresistance across multiple cancer and disease contexts [PMID:37303063, PMID:37907465, PMID:42002123, PMID:41860570].","teleology":[{"year":2018,"claim":"Resolved whether and how B4GALT1 self-assembles and links its quaternary structure to catalysis, establishing the conformational basis of substrate binding.","evidence":"X-ray crystallography of the wild-type homodimer plus catalytic-residue mutagenesis and live-cell FRET","pmids":["30352055"],"confidence":"High","gaps":["Does not define how the silencing homomer is relieved in vivo","No structure of the active heteromer"]},{"year":2019,"claim":"Showed that B4GALT1 and ST6GAL1 form catalytically required heteromers via distinct surfaces, explaining how sequential N-glycan elaboration is organized within the Golgi.","evidence":"Molecular docking, mutagenesis screens, and high-throughput FRET in live cells","pmids":["31395657"],"confidence":"High","gaps":["Interaction surfaces inferred from docking/FRET rather than a co-structure","Stoichiometry and dynamics of the heteromer in situ unresolved"]},{"year":2019,"claim":"Connected B4GALT1 galactosylation to a specific clinical lipoprotein phenotype by demonstrating CETP hypogalactosylation and reduced activity in CDG patients.","evidence":"Isoelectric focusing, CETP glycoform western blot, and activity assays in patient plasma","pmids":["31800099"],"confidence":"Medium","gaps":["Does not prove direct CETP modification by B4GALT1","Causality to HDL particle size inferred from patient correlation"]},{"year":2021,"claim":"Established a causal, quantitative link between B4GALT1 enzymatic activity and systemic lipoprotein/coagulation metabolism through a hypomorphic human variant and a knock-in mouse.","evidence":"In vitro activity assay of mutant vs WT, serum N-glycan profiling, and 353Ser knock-in mice","pmids":["34855475"],"confidence":"High","gaps":["Specific glycoproteins driving the LDL-C/fibrinogen effects not pinpointed","Tissue-of-origin for the serum phenotype unresolved"]},{"year":2023,"claim":"Identified site-specific protein substrates of B4GALT1 (integrin α6/β1), showing glycosylation tunes integrin–laminin binding and tumor cell invasion.","evidence":"Mass spectrometry substrate ID, GSL-II lectin pull-down, KO/KD, antibody rescue, and lung metastasis model","pmids":["37907465"],"confidence":"High","gaps":["Exact glycan structures on each integrin not mapped","Mechanism linking altered glycans to affinity not structurally defined"]},{"year":2023,"claim":"Extended B4GALT1 function to immune evasion by showing it stabilizes PD-L1 directly and TAZ to drive PD-L1 transcription.","evidence":"Glycosylation and protein-stability assays, transcriptional reporters, and loss-of-function studies","pmids":["37303063"],"confidence":"Medium","gaps":["Glycosylation sites on PD-L1/TAZ not defined","Direct vs indirect stabilization not fully separated"]},{"year":2026,"claim":"Demonstrated substrate- and site-specific glycosylation governing inflammatory (IL-1R1 N193) and metabolic/ferroptotic (PPARγ) signaling, broadening the disease reach of B4GALT1.","evidence":"Co-IP, PNGase F, site-directed mutagenesis, conditional/AAV knockdown mice in OA and MASLD models","pmids":["42002123","41860570"],"confidence":"High","gaps":["PPARγ glycosylation site not specified","How glycosylation flips stability up (IL-1R1) versus down (PPARγ) is unexplained"]},{"year":2025,"claim":"Revealed a catalysis-independent trafficking role: B4GALT1 retains LRP5/6 in the Golgi to dampen WNT signaling, with Wntless competing for the interaction.","evidence":"Co-IP, cell surface translocation assays, and LGK974 pharmacology","pmids":["41182165"],"confidence":"Medium","gaps":["Whether retention requires galactosyltransferase activity unresolved","Structural basis of B4GALT1–LRP5/6 and B4GALT1–Wntless binding unknown"]},{"year":2025,"claim":"Showed enzyme function is metabolically gated, with UDP-Gal availability controlling B4GALT1–SLC35A2 complex assembly.","evidence":"CRISPR knockout of GALE/GALT, NanoBiT PPI assay, and N-glycan profiling in HEK293T","pmids":["40230451"],"confidence":"Medium","gaps":["Mechanism by which UDP-Gal promotes complex formation not defined","Physiological conditions under which this gating operates unclear"]},{"year":2025,"claim":"Mapped a broad regulatory network (transcriptional and post-transcriptional) positioning B4GALT1 as both an oncogenic effector and context-dependent tumor suppressor controlling chemoresistance.","evidence":"Reporter, RNAi/overexpression rescue, Co-IP, and ubiquitination assays across leukemia, prostate, and esophageal cancer models","pmids":["23024026","27516205","27797721","32902124","40097806"],"confidence":"Medium","gaps":["Context-dependence of oncogenic vs suppressor roles not reconciled","Many links are correlative or single-lab"]},{"year":2025,"claim":"Preprint evidence proposes B4GALT1 galactosylates TCR/CD8 to limit T-cell activation and elongates NOTCH O-glucose glycans to modulate Notch signaling, expanding its substrate repertoire to immune receptors and developmental signaling.","evidence":"CRISPR screens with AP-MS substrate ID and rescue (TCR/CD8); MS, mutagenesis, and Notch reporters (NOTCH1/3) — both preprints","pmids":[],"confidence":"Medium","gaps":["Not peer-reviewed","TCR/CD8 and NOTCH substrate claims await independent confirmation"]},{"year":null,"claim":"It remains unresolved how B4GALT1 achieves substrate selectivity that produces opposite fates (stabilization vs destabilization) and how catalytic versus non-catalytic (trafficking) functions are partitioned in vivo.","evidence":"No timeline study reconciles substrate-specific outcomes with a unifying recognition or regulatory mechanism","pmids":[],"confidence":"Low","gaps":["No structural model of substrate-specific recognition","Catalysis-dependent vs catalysis-independent roles not cleanly separated","Glycan-structure-to-phenotype mapping incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,1,2,5,18]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[3,4,5,8,9]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,7,10]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1,2,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[7,16]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[3,8]}],"complexes":[],"partners":["ST6GAL1","SLC35A2","LRP5","LRP6","IL1R1","CDK11","UBE2Q1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P15291","full_name":"Beta-1,4-galactosyltransferase 1","aliases":["Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase","Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase","Lactose synthase A protein","N-acetyllactosamine synthase","Nal synthase","Neolactotriaosylceramide beta-1,4-galactosyltransferase","UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 1","UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 1"],"length_aa":398,"mass_kda":43.9,"function":"Galactosyltransferase acting in the Golgi stacks. Catalyzes the transfer of galactose (Gal) from UDP-alpha-D-galactose in beta(1->4) linkage to the non-reducing terminal N-acetylglucosamine (GlcNAc) moieties of glycolipids and complex-type N-linked glycans (PubMed:16157350, PubMed:27872474, PubMed:29133956, PubMed:36280670, PubMed:37632720, PubMed:38321209). Adds one Gal residue to both GlcNAc beta(1->2)-linked to the alpha(1->3) and alpha(1->6) mannose antennae of complex-type N-glycans, enabling the formation of mono- and di-galactosylated glycoforms. Galactosylates complex-type N-glycans attached on the fragment crystallizable (Fc) of immunoglobulin-gamma isotypes (IgGs), a prerequisite for antibody glycan sialylation and related anti-inflammatory effector functions (PubMed:27872474, PubMed:29133956, PubMed:36280670, PubMed:37632720). Can also transfer a Gal residue to free GlcNAc to form N-acetyllactosamine (PubMed:16157350). With LALBA/alpha-lactalbumin forms the lactose synthase complex responsible for production of large amounts of lactose in the lactating mammary gland. Interaction with LALBA alters the sugar substrate specificity of the catalytic domain, enabling high affinity binding of glucose and its transformation to lactose (PubMed:16157350) The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, like those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix. Acts as a sperm receptor for ZP3 O-linked glycans on the zona pellucida leading to activation of G-protein signaling and acrosome reaction The secreted form is proficient in galactosyltransferase activity and could be involved in glycan remodeling in biological fluids","subcellular_location":"Secreted","url":"https://www.uniprot.org/uniprotkb/P15291/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/B4GALT1","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/B4GALT1","total_profiled":1310},"omim":[{"mim_id":"620364","title":"COMBINED LOW LDL AND FIBRINOGEN; CLDLFIB","url":"https://www.omim.org/entry/620364"},{"mim_id":"616615","title":"CHONDROITIN SULFATE N-ACETYLGALACTOSAMINYLTRANSFERASE 1; CSGALNACT1","url":"https://www.omim.org/entry/616615"},{"mim_id":"609182","title":"SOLUTE CARRIER FAMILY 35, MEMBER D2; SLC35D2","url":"https://www.omim.org/entry/609182"},{"mim_id":"607091","title":"CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IId; CDG2D","url":"https://www.omim.org/entry/607091"},{"mim_id":"605517","title":"BETA-1,4-GLUCURONYLTRANSFERASE 1; B4GAT1","url":"https://www.omim.org/entry/605517"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Golgi apparatus","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/B4GALT1"},"hgnc":{"alias_symbol":["beta4Gal-T1"],"prev_symbol":["GGTB2"]},"alphafold":{"accession":"P15291","domains":[{"cath_id":"3.90.550.10","chopping":"152-343_377-394","consensus_level":"high","plddt":97.8285,"start":152,"end":394}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P15291","model_url":"https://alphafold.ebi.ac.uk/files/AF-P15291-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P15291-F1-predicted_aligned_error_v6.png","plddt_mean":83.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=B4GALT1","jax_strain_url":"https://www.jax.org/strain/search?query=B4GALT1"},"sequence":{"accession":"P15291","fasta_url":"https://rest.uniprot.org/uniprotkb/P15291.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P15291/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P15291"}},"corpus_meta":[{"pmid":"37303063","id":"PMC_37303063","title":"B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma.","date":"2023","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/37303063","citation_count":66,"is_preprint":false},{"pmid":"30182452","id":"PMC_30182452","title":"LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity.","date":"2018","source":"Cell proliferation","url":"https://pubmed.ncbi.nlm.nih.gov/30182452","citation_count":62,"is_preprint":false},{"pmid":"33309857","id":"PMC_33309857","title":"Galactosyltransferase B4GALT1 confers chemoresistance in pancreatic ductal adenocarcinomas by upregulating N-linked glycosylation of CDK11p110.","date":"2020","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/33309857","citation_count":42,"is_preprint":false},{"pmid":"30912138","id":"PMC_30912138","title":"lncRNA B4GALT1-AS1 promotes colon cancer cell stemness and migration by recruiting YAP to the nucleus and enhancing YAP transcriptional activity.","date":"2019","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30912138","citation_count":38,"is_preprint":false},{"pmid":"31395657","id":"PMC_31395657","title":"Assembly of B4GALT1/ST6GAL1 heteromers in the Golgi membranes involves lateral interactions via highly charged surface domains.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31395657","citation_count":38,"is_preprint":false},{"pmid":"27516205","id":"PMC_27516205","title":"MiR-124-3p/B4GALT1 axis plays an important role in SOCS3-regulated growth and chemo-sensitivity of CML.","date":"2016","source":"Journal of hematology & oncology","url":"https://pubmed.ncbi.nlm.nih.gov/27516205","citation_count":34,"is_preprint":false},{"pmid":"27092876","id":"PMC_27092876","title":"Increased B4GALT1 expression associates with adverse outcome in patients with non-metastatic clear cell renal cell carcinoma.","date":"2016","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27092876","citation_count":29,"is_preprint":false},{"pmid":"29862652","id":"PMC_29862652","title":"CRISPR/Cas9-Multiplexed Editing of Chinese Hamster Ovary B4Gal-T1, 2, 3, and 4 Tailors N-Glycan Profiles of Therapeutics and Secreted Host Cell Proteins.","date":"2018","source":"Biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/29862652","citation_count":25,"is_preprint":false},{"pmid":"34855475","id":"PMC_34855475","title":"Genetic and functional evidence links a missense variant in B4GALT1 to lower LDL and fibrinogen.","date":"2021","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/34855475","citation_count":24,"is_preprint":false},{"pmid":"23024026","id":"PMC_23024026","title":"B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line.","date":"2012","source":"IUBMB life","url":"https://pubmed.ncbi.nlm.nih.gov/23024026","citation_count":23,"is_preprint":false},{"pmid":"32902124","id":"PMC_32902124","title":"The AKR1C3/AR-V7 complex maintains CRPC tumour growth by repressing B4GALT1 expression.","date":"2020","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32902124","citation_count":22,"is_preprint":false},{"pmid":"31717588","id":"PMC_31717588","title":"B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells.","date":"2019","source":"Journal of clinical medicine","url":"https://pubmed.ncbi.nlm.nih.gov/31717588","citation_count":22,"is_preprint":false},{"pmid":"30352055","id":"PMC_30352055","title":"The dimeric structure of wild-type human glycosyltransferase B4GalT1.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30352055","citation_count":21,"is_preprint":false},{"pmid":"26315939","id":"PMC_26315939","title":"Multifaceted roles of 5'-regulatory region of the cancer associated gene B4GALT1 and its comparison with the gene family.","date":"2015","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/26315939","citation_count":21,"is_preprint":false},{"pmid":"21920538","id":"PMC_21920538","title":"B4GALT1-congenital disorders of glycosylation presents as a non-neurologic glycosylation disorder with hepatointestinal involvement.","date":"2011","source":"The Journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/21920538","citation_count":19,"is_preprint":false},{"pmid":"33287670","id":"PMC_33287670","title":"B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo.","date":"2020","source":"Technology in cancer research & treatment","url":"https://pubmed.ncbi.nlm.nih.gov/33287670","citation_count":18,"is_preprint":false},{"pmid":"33238000","id":"PMC_33238000","title":"Increased B4GALT1 expression is associated with platelet surface galactosylation and thrombopoietin plasma levels in MPNs.","date":"2021","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/33238000","citation_count":16,"is_preprint":false},{"pmid":"37907465","id":"PMC_37907465","title":"Decreased B4GALT1 promotes hepatocellular carcinoma cell invasiveness by regulating the laminin-integrin pathway.","date":"2023","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/37907465","citation_count":14,"is_preprint":false},{"pmid":"31800099","id":"PMC_31800099","title":"Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.","date":"2019","source":"Journal of inherited metabolic disease","url":"https://pubmed.ncbi.nlm.nih.gov/31800099","citation_count":10,"is_preprint":false},{"pmid":"32157688","id":"PMC_32157688","title":"B4GALT1-congenital disorders of glycosylation: Expansion of the phenotypic and molecular spectrum and review of the literature.","date":"2020","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32157688","citation_count":10,"is_preprint":false},{"pmid":"39231945","id":"PMC_39231945","title":"B4GALT1-dependent galectin-8 binding with TGF-β receptor suppresses colorectal cancer progression and metastasis.","date":"2024","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/39231945","citation_count":9,"is_preprint":false},{"pmid":"36499368","id":"PMC_36499368","title":"B4GALT1 as a New Biomarker of Idiopathic Pulmonary Fibrosis.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36499368","citation_count":8,"is_preprint":false},{"pmid":"35402178","id":"PMC_35402178","title":"LncRNA B4GALT1-AS1 promotes non-small cell lung cancer cell growth via increasing ZEB1 level by sponging miR-144-3p.","date":"2022","source":"Translational cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/35402178","citation_count":8,"is_preprint":false},{"pmid":"37328064","id":"PMC_37328064","title":"In-Depth Mass Spectrometry Analysis Reveals the Plasma Proteomic and N-Glycoproteomic Impact of an Amish-Enriched Cardioprotective Variant in B4GALT1.","date":"2023","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/37328064","citation_count":8,"is_preprint":false},{"pmid":"33427026","id":"PMC_33427026","title":"Identification of novel single-nucleotide polymorphism at exon1 and 2 region of B4GALT1 gene and its association with milk production traits in crossbred cattle of Kerala, India.","date":"2021","source":"Animal biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/33427026","citation_count":6,"is_preprint":false},{"pmid":"33014162","id":"PMC_33014162","title":"Long non-coding RNA B4GALT1-Antisense RNA 1/microRNA-30e/SRY-box transcription factor 9 signaling axis contributes to non-small cell lung cancer cell growth.","date":"2020","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/33014162","citation_count":6,"is_preprint":false},{"pmid":"35267641","id":"PMC_35267641","title":"The B-Cell-Specific Ablation of B4GALT1 Reduces Cancer Formation and Reverses the Changes in Serum IgG Glycans during the Induction of Mouse Hepatocellular Carcinoma.","date":"2022","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/35267641","citation_count":5,"is_preprint":false},{"pmid":"38326326","id":"PMC_38326326","title":"Downregulation of long noncoding RNA B4GALT1-AS1 is associated with breast cancer development.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38326326","citation_count":3,"is_preprint":false},{"pmid":"31852463","id":"PMC_31852463","title":"Identification of the complete coding cDNAs and expression analysis of B4GALT1, LALBA, ST3GAL5, ST6GAL1 in the colostrum and milk of the Garganica and Maltese goat breeds to reveal possible implications for oligosaccharide biosynthesis.","date":"2019","source":"BMC veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/31852463","citation_count":3,"is_preprint":false},{"pmid":"40097806","id":"PMC_40097806","title":"SPOP/NOLC1/B4GALT1 signaling axis enhances paclitaxel resistance in endometrial cancer by inducing O-dysglycosylation.","date":"2025","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/40097806","citation_count":2,"is_preprint":false},{"pmid":"27797721","id":"PMC_27797721","title":"ZFX modulates the growth of human leukemic cells via B4GALT1.","date":"2016","source":"Acta biochimica et biophysica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/27797721","citation_count":2,"is_preprint":false},{"pmid":"40230451","id":"PMC_40230451","title":"Cytosolic UDP-Gal biosynthetic machinery is required for dimerization of SLC35A2 in the Golgi membrane and its interaction with B4GalT1.","date":"2025","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/40230451","citation_count":2,"is_preprint":false},{"pmid":"37198983","id":"PMC_37198983","title":"Analysis of the Interaction of UBE2Q1 with B4GALT1 and P53: Experimental and Molecular Modeling Study.","date":"2023","source":"Protein and peptide letters","url":"https://pubmed.ncbi.nlm.nih.gov/37198983","citation_count":1,"is_preprint":false},{"pmid":"41182165","id":"PMC_41182165","title":"B4GALT1 and Wntless collaborate to block LRP5/6 translocation from Golgi to cell surface.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/41182165","citation_count":0,"is_preprint":false},{"pmid":"40460949","id":"PMC_40460949","title":"Bioinformatics prediction and experimental verification identify B4GALT1 as a diagnostic biomarker of glioblastoma.","date":"2025","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40460949","citation_count":0,"is_preprint":false},{"pmid":"42200454","id":"PMC_42200454","title":"Nascent Pre-Platelets and B4GALT1 Glycosylation Contribute to 5-FU-induced Bone Marrow Recovery.","date":"2026","source":"Blood advances","url":"https://pubmed.ncbi.nlm.nih.gov/42200454","citation_count":0,"is_preprint":false},{"pmid":"42002123","id":"PMC_42002123","title":"B4GALT1 drives osteoarthritis progression by stabilizing IL-1R1 through N-linked glycosylation.","date":"2026","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/42002123","citation_count":0,"is_preprint":false},{"pmid":"41860570","id":"PMC_41860570","title":"B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis.","date":"2026","source":"Hepatology communications","url":"https://pubmed.ncbi.nlm.nih.gov/41860570","citation_count":0,"is_preprint":false},{"pmid":"32027290","id":"PMC_32027290","title":"[Effect of B4GALT1 on Proliferation of Its Co-cultured Human Acute Myeloid Leukemia Cell Line in Bone Marrow Stromal Cells].","date":"2020","source":"Zhongguo shi yan xue ye xue za zhi","url":"https://pubmed.ncbi.nlm.nih.gov/32027290","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.10.30.685343","title":"ADAR RNA editing for cardiovascular disease: Targeting  <i>B4GALT1</i>  to modulate lipid metabolism through reduced galactosyltransferase activity","date":"2025-10-31","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.30.685343","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.08.20.671236","title":"Ex vivo and in vivo CRISPR/Cas9 screenings identify the roles of protein N-glycosylation in regulating T-cell activation and functions","date":"2025-08-24","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.20.671236","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.25.634886","title":"Glycan-Mediated Mechanosensing Regulates Megakaryocyte-Biased Hematopoietic Stem Cell Subsets","date":"2025-01-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.25.634886","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.02.20.639268","title":"Differential  <i>O</i>  -Glc elongation on the specific EGF repeat within a ligand binding domain regulates NOTCH1 signaling","date":"2025-02-25","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.20.639268","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":25003,"output_tokens":5828,"usd":0.081214,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14229,"output_tokens":3809,"usd":0.083185,"stage2_stop_reason":"end_turn"},"total_usd":0.164399,"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\": 2019,\n      \"finding\": \"B4GALT1 and ST6GAL1 interact via highly charged noncatalytic surfaces (leaving active sites exposed), forming heteromers in the Golgi that are required for their full catalytic activity in sequential N-glycan modification. B4GALT1 uses its active-site surface for homomeric assembly, which silences its catalytic activity, whereas ST6GAL1 uses the same noncatalytic surface for both homomers and heteromers.\",\n      \"method\": \"Molecular docking simulations, mutagenesis screens, high-throughput FRET analyses in live cells, structural modeling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (docking, mutagenesis, FRET in live cells) in a single rigorous study establishing interaction surfaces and catalytic consequences\",\n      \"pmids\": [\"31395657\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Wild-type human B4GALT1 exists as a homodimer in dynamic equilibrium with monomer; crystal structures revealed B4GALT1 in both open and closed conformations of the Trp loop and lid regions responsible for donor and acceptor substrate binding. Targeted mutagenesis of key catalytic amino acids impaired homomer formation in vivo, linking catalytic residues to dimer assembly.\",\n      \"method\": \"X-ray crystallography (crystal structure of wild-type homodimer), targeted mutagenesis, FRET assays in live cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutagenesis plus FRET functional validation in a single study\",\n      \"pmids\": [\"30352055\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A missense variant p.Asn352Ser in the functional domain of B4GALT1 reduces galactosyltransferase activity by ~50% compared to wild-type. Carriers show decreased galactosylation and sialylation of ApoB100, fibrinogen, IgG, and transferrin in serum, and B4galt1 353Ser knock-in mice show decreases in LDL-C and fibrinogen, establishing B4GALT1 galactosyltransferase activity as a regulator of lipoprotein and coagulation factor metabolism.\",\n      \"method\": \"In vitro galactosyltransferase activity assay with mutant vs. wild-type protein, N-linked glycan profiling of human serum, knock-in mouse model\",\n      \"journal\": \"Science (New York, N.Y.)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro enzyme assay with mutagenesis, human glycan profiling, and knock-in mouse model providing multiple orthogonal lines of evidence\",\n      \"pmids\": [\"34855475\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"B4GALT1 directly mediates N-linked glycosylation of PD-L1 protein, preventing its proteasomal degradation (posttranscriptional stabilization). Additionally, B4GALT1 stabilizes TAZ protein via glycosylation, which in turn activates CD274 (PD-L1) transcription, thereby promoting immune escape in lung adenocarcinoma.\",\n      \"method\": \"In vitro and in vivo functional/mechanistic experiments including glycosylation assays, protein stability assays, transcriptional reporter assays, loss-of-function studies\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — mechanistic follow-up with multiple in vitro and in vivo approaches; abstract does not specify full reconstitution or structural validation\",\n      \"pmids\": [\"37303063\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"B4GALT1 interacts with and stabilizes CDK11p110 via N-linked glycosylation, downstream of p65 transcriptional upregulation of B4GALT1, forming a p65-B4GALT1-CDK11p110 signaling axis that promotes chemoresistance in pancreatic ductal adenocarcinoma.\",\n      \"method\": \"Co-immunoprecipitation, glycosylation assays, genetic perturbation of B4GALT1 in cell lines, orthotopic PDAC mouse model\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP and glycosylation assays plus in vivo model in a single lab; mechanistic interaction established but full reconstitution not described\",\n      \"pmids\": [\"33309857\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"B4GALT1 modifies the N-glycans of integrin α6 and integrin β1, and its loss increases laminin-binding activity of these integrins, promoting HCC cell migration and invasion. Integrins α6 and β1 were identified as main protein substrates of B4GALT1 by mass spectrometry and GSL-II lectin pull-down.\",\n      \"method\": \"Mass spectrometry-based substrate identification, Griffonia simplicifolia lectin II (GSL-II) pull-down, B4GALT1 knockdown/knockout, integrin-blocking antibody rescue experiments, in vivo lung metastasis model\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (MS substrate ID, lectin pull-down, KO/KD, antibody rescue, in vivo) establishing B4GALT1 as the N-glycosylating enzyme for integrin α6/β1\",\n      \"pmids\": [\"37907465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In B4GALT1-CDG patients, cholesteryl ester transfer protein (CETP) is hypoglycosylated (specifically hypogalactosylated) and exhibits reduced enzymatic activity, resulting in large HDL particles and altered lipoprotein homeostasis, directly linking B4GALT1-mediated galactosylation to CETP function.\",\n      \"method\": \"Isoelectric focusing, western blot of CETP glyco-isoforms, CETP activity assay in patient plasma vs. controls\",\n      \"journal\": \"Journal of inherited metabolic disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical activity assay and glycoform analysis in human patients; single study but uses orthogonal methods\",\n      \"pmids\": [\"31800099\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"B4GALT1 interacts with LRP5/6 in the Golgi, causing their retention and reducing LRP5/6 surface translocation, thereby attenuating WNT/β-catenin signaling. B4GALT1 also binds Wntless; Wnt secretion occupying Wntless antagonizes B4GALT1-mediated LRP5/6 retention. Pharmacological uncoupling of Wnt/Wntless with LGK974 enhances LRP5/6 Golgi retention.\",\n      \"method\": \"Co-immunoprecipitation, cell surface translocation assays, pharmacological inhibition (LGK974), loss-of-function studies\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP and functional cell-based assays in a single study; mechanistic interaction with LRP5/6 and Wntless established\",\n      \"pmids\": [\"41182165\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"B4GALT1 directly interacts with IL-1R1 and promotes its N-linked glycosylation specifically at the N193 site, thereby enhancing IL-1R1 protein stability and downstream inflammatory signaling in chondrocytes. AAV-mediated knockdown of B4GALT1 in vivo reduced IL-1R1 protein levels and attenuated cartilage degeneration.\",\n      \"method\": \"Co-immunoprecipitation, PNGase F treatment, site-directed mutagenesis (N193 site), AAV-mediated in vivo knockdown, DMM mouse OA model\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — Co-IP, site-directed mutagenesis of glycosylation site, PNGase F, and in vivo AAV knockdown providing multiple orthogonal methods in a single study\",\n      \"pmids\": [\"42002123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"B4GALT1-mediated N-glycosylation of PPARγ destabilizes PPARγ protein; B4GALT1 deficiency impairs PPARγ N-glycosylation, leading to PPARγ stabilization, which transcriptionally represses ACSL4, thereby reducing lipid peroxidation and ferroptosis in hepatocytes during MASLD progression.\",\n      \"method\": \"Hepatocyte-specific B4galt1-knockout mice (CDAHFD model), N-glycosylation assays, gene expression analysis, PPARγ overexpression rescue experiment\",\n      \"journal\": \"Hepatology communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — conditional knockout mouse model plus glycosylation and rescue experiments; single lab, abstract does not detail reconstitution\",\n      \"pmids\": [\"41860570\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Knockout of GALE (UDP-galactose 4'-epimerase), which reduces intracellular UDP-Gal levels, diminishes the ability of the UDP-Gal transporter SLC35A2 to form homomers and to interact with B4GALT1 in the Golgi, indicating that nucleotide sugar availability regulates B4GALT1-SLC35A2 complex formation.\",\n      \"method\": \"CRISPR/Cas9 knockout of GALE and GALT in HEK293T cells, NanoBiT protein-protein interaction assay, N-glycan profiling\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO with NanoBiT PPI assay and glycan profiling; single lab, two orthogonal methods\",\n      \"pmids\": [\"40230451\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"B4GALT1 knockdown in K562/ADR leukemia cells downregulated the Hedgehog signaling pathway and reversed multidrug resistance in vitro and in vivo, identifying a functional link between B4GALT1-mediated galactosylation and Hedgehog pathway activity in chemoresistance.\",\n      \"method\": \"RNA interference knockdown, enzyme activity assays, lectin blotting, in vitro drug sensitivity assays, in vivo tumor models\",\n      \"journal\": \"IUBMB life\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RNAi knockdown with enzyme activity assays, lectin blotting, and in vivo validation; single lab\",\n      \"pmids\": [\"23024026\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"SOCS3 upregulates miR-124-3p, which targets B4GALT1 mRNA, forming a SOCS3/miR-124-3p/B4GALT1 axis that regulates growth and chemosensitivity of CML cells. Luciferase reporter assay confirmed B4GALT1 as a direct target of miR-124-3p.\",\n      \"method\": \"Luciferase reporter assay, qPCR, western blotting, CCK-8 assay, tumorigenicity assays in nude mice\",\n      \"journal\": \"Journal of hematology & oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — luciferase reporter validation of miR-124-3p targeting B4GALT1, with in vitro and in vivo functional assays; single lab\",\n      \"pmids\": [\"27516205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ZFX transcription factor positively regulates B4GALT1 expression in leukemic cells; ZFX silencing decreases B4GALT1 expression and glycoprotein galactosylation. Overexpression of B4GALT1 restored growth and drug resistance in ZFX-silenced cells, placing B4GALT1 downstream of ZFX.\",\n      \"method\": \"RNAi silencing of ZFX, gene expression analysis, lectin blot assay for galactosylation, B4GALT1 overexpression rescue\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — RNAi + overexpression rescue + lectin blotting in a single lab study\",\n      \"pmids\": [\"27797721\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"AKR1C3 interacts with AR-V7 protein in CRPC cells, and this complex represses B4GALT1 expression; B4GALT1 is identified as a tumor suppressor gene in prostate cancer downstream of this complex. The AKR1C3/AR-V7 complex also reciprocally inhibits each other's protein degradation.\",\n      \"method\": \"Co-immunoprecipitation (AKR1C3/AR-V7 interaction), gene expression analysis, in vitro and in vivo tumor growth assays\",\n      \"journal\": \"Journal of cellular and molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP for AKR1C3/AR-V7 interaction, with B4GALT1 identified as downstream target via expression analysis; single lab\",\n      \"pmids\": [\"32902124\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"NOLC1 acts as a transcription factor to activate B4GALT1 transcriptional expression; SPOP (E3 ubiquitin ligase adaptor) mediates ubiquitination and degradation of NOLC1. ECa-associated SPOP mutants abrogate NOLC1 ubiquitination, leading to NOLC1 accumulation and B4GALT1 upregulation, causing abnormal glycosylation and paclitaxel resistance.\",\n      \"method\": \"Co-IP for SPOP-NOLC1 interaction, ubiquitination assays, transcriptional reporter assays, B4GALT1 knockdown rescue, in vitro and in vivo functional assays\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP, ubiquitination assay, and transcriptional reporter with rescue experiments; single lab\",\n      \"pmids\": [\"40097806\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Galectin-8 interacts with the type II TGF-β receptor and competes with TGF-β binding, suppressing TGF-β-driven EMT and CRC metastasis. The anti-migratory effect of galectin-8 depends on B4GALT1, which modifies N-glycans on TGF-β receptor, establishing B4GALT1 as required for galectin-8 ligand recognition at the TGF-β receptor.\",\n      \"method\": \"Co-immunoprecipitation (galectin-8/TGF-βRII), B4GALT1 depletion experiments, migration assays, intra-splenic injection tumor model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP and B4GALT1 depletion functional assays plus in vivo model; single lab\",\n      \"pmids\": [\"39231945\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"B4GALT1 galactosylates TCR and CD8 co-receptor components on the CD8+ T-cell surface, and this galactosylation reduces the interaction between TCR and CD8 that is essential for TCR activation. B4GALT1 inactivation enhances TCR-T cell functions but has no effect on CAR-T cells. Substrates were systematically identified by affinity purification and mass spectrometry.\",\n      \"method\": \"CRISPR/Cas9 genome-wide and custom screens, affinity purification-mass spectrometry for substrate identification, TCR-CD8 fusion protein rescue, syngeneic mouse tumor model\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR screens, AP-MS substrate identification, and genetic rescue; preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"B4GALT1 catalyzes galactose elongation of O-glucose glycans specifically on NOTCH1 EGF10 (and NOTCH3 EGF9), forming a 3'-sialyllactose-like structure in cooperation with ST3GAL4. This site-specific elongation significantly impacts NOTCH1 ligand binding and signal transduction. Mutagenesis identified the amino acid at position -2 of the fourth cysteine as critical for galactose elongation.\",\n      \"method\": \"Mass spectrometry for modification identification, site-directed mutagenesis, ligand-binding assays, Notch signaling reporter assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — MS identification, mutagenesis, and functional Notch signaling assays; preprint, single lab\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"UBE2Q1 (an E2 ubiquitin-conjugating enzyme) can interact with B4GALT1 protein as demonstrated by co-immunoprecipitation in colorectal cancer cells overexpressing UBE2Q1, and molecular docking confirmed high-affinity interaction between the UBC domain of UBE2Q1 and B4GALT1.\",\n      \"method\": \"Co-immunoprecipitation (IP/silver staining), molecular docking (MOE software)\",\n      \"journal\": \"Protein and peptide letters\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP without reciprocal confirmation, supported only by computational docking; single lab, single method\",\n      \"pmids\": [\"37198983\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In bone marrow stromal cells, B4GALT1 expression is positively regulated by the upstream transcription factor c-Jun (via JNK/c-Jun pathway), validated by dual luciferase reporter assay. Overexpression of B4GALT1 in stromal cells promoted proliferation of co-cultured AML cells.\",\n      \"method\": \"Dual luciferase reporter assay, JNK/c-Jun inhibitor treatment, co-culture proliferation assay by flow cytometry\",\n      \"journal\": \"Zhongguo shi yan xue ye xue za zhi\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — luciferase reporter for upstream regulation; single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"32027290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In myeloproliferative neoplasm megakaryocytes, increased B4GALT1 expression leads to elevated LacNAc (β4-N-acetyllactosamine/Galβ1,4GlcNAc) expression on platelets, which promotes hepatic thrombopoietin (TPO) synthesis independently of platelet mass, linking B4GALT1-mediated galactosylation to TPO regulation.\",\n      \"method\": \"B4GALT1 gene expression analysis in patient megakaryocytes, LacNAc expression assays on platelets, JAK1/2 inhibitor treatment experiments\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — patient-derived megakaryocytes with LacNAc functional assays and pharmacological inhibition; single lab\",\n      \"pmids\": [\"33238000\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"B4GALT1 is a Golgi-resident β-1,4-galactosyltransferase that assembles into catalytically regulated homodimers (active-site surfaces mediate silencing homomer) and functional heteromers with ST6GAL1 (via noncatalytic charged surfaces) to sequentially galactosylate N-glycans; it directly N-glycosylates specific substrates including PD-L1, TAZ, CDK11p110, integrin α6/β1, IL-1R1, PPARγ, TCR/CD8 components, and LRP5/6, thereby regulating their stability, ligand binding, or trafficking, and its galactosyltransferase activity (reducible by the p.Asn352Ser variant) controls lipoprotein metabolism, coagulation factor function, and immune signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"B4GALT1 is a Golgi-resident β-1,4-galactosyltransferase that adds galactose to N-glycans and whose activity is subject to assembly-level control: wild-type enzyme exists in monomer–homodimer equilibrium, with catalytic-residue surfaces mediating a silencing homomer, while interaction with ST6GAL1 through noncatalytic charged surfaces forms heteromers required for full sequential N-glycan modification [#0, #1]. Complex formation with the UDP-galactose transporter SLC35A2 is gated by nucleotide-sugar availability, coupling enzyme output to substrate supply [#10]. A p.Asn352Ser variant lowers galactosyltransferase activity by ~50%, reducing galactosylation of ApoB100, fibrinogen, IgG, and transferrin and lowering LDL-C and fibrinogen in knock-in mice, establishing B4GALT1 as a regulator of lipoprotein and coagulation factor metabolism [#2]; consistent with this, loss of B4GALT1-dependent galactosylation hypoglycosylates and inactivates CETP, altering HDL homeostasis [#6]. Beyond bulk glycoprotein processing, B4GALT1 site-specifically glycosylates defined substrates to control their stability, ligand binding, or trafficking: it N-glycosylates and stabilizes PD-L1, TAZ, CDK11p110, and IL-1R1 (at N193), destabilizes PPARγ, modifies integrin α6/β1 to restrain laminin binding, and modifies the TGF-β receptor as required for galectin-8 recognition [#3, #4, #8, #9, #5, #16]. Independent of catalysis, B4GALT1 binds LRP5/6 in the Golgi and retains them intracellularly to attenuate WNT/β-catenin signaling, a retention antagonized by Wntless engagement [#7]. Through these substrate-specific actions B4GALT1 influences immune escape, inflammatory and ferroptotic signaling, integrin-driven migration, and chemoresistance across multiple cancer and disease contexts [#3, #5, #8, #9].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved whether and how B4GALT1 self-assembles and links its quaternary structure to catalysis, establishing the conformational basis of substrate binding.\",\n      \"evidence\": \"X-ray crystallography of the wild-type homodimer plus catalytic-residue mutagenesis and live-cell FRET\",\n      \"pmids\": [\"30352055\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not define how the silencing homomer is relieved in vivo\", \"No structure of the active heteromer\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed that B4GALT1 and ST6GAL1 form catalytically required heteromers via distinct surfaces, explaining how sequential N-glycan elaboration is organized within the Golgi.\",\n      \"evidence\": \"Molecular docking, mutagenesis screens, and high-throughput FRET in live cells\",\n      \"pmids\": [\"31395657\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Interaction surfaces inferred from docking/FRET rather than a co-structure\", \"Stoichiometry and dynamics of the heteromer in situ unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Connected B4GALT1 galactosylation to a specific clinical lipoprotein phenotype by demonstrating CETP hypogalactosylation and reduced activity in CDG patients.\",\n      \"evidence\": \"Isoelectric focusing, CETP glycoform western blot, and activity assays in patient plasma\",\n      \"pmids\": [\"31800099\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not prove direct CETP modification by B4GALT1\", \"Causality to HDL particle size inferred from patient correlation\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Established a causal, quantitative link between B4GALT1 enzymatic activity and systemic lipoprotein/coagulation metabolism through a hypomorphic human variant and a knock-in mouse.\",\n      \"evidence\": \"In vitro activity assay of mutant vs WT, serum N-glycan profiling, and 353Ser knock-in mice\",\n      \"pmids\": [\"34855475\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific glycoproteins driving the LDL-C/fibrinogen effects not pinpointed\", \"Tissue-of-origin for the serum phenotype unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified site-specific protein substrates of B4GALT1 (integrin α6/β1), showing glycosylation tunes integrin–laminin binding and tumor cell invasion.\",\n      \"evidence\": \"Mass spectrometry substrate ID, GSL-II lectin pull-down, KO/KD, antibody rescue, and lung metastasis model\",\n      \"pmids\": [\"37907465\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Exact glycan structures on each integrin not mapped\", \"Mechanism linking altered glycans to affinity not structurally defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended B4GALT1 function to immune evasion by showing it stabilizes PD-L1 directly and TAZ to drive PD-L1 transcription.\",\n      \"evidence\": \"Glycosylation and protein-stability assays, transcriptional reporters, and loss-of-function studies\",\n      \"pmids\": [\"37303063\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Glycosylation sites on PD-L1/TAZ not defined\", \"Direct vs indirect stabilization not fully separated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Demonstrated substrate- and site-specific glycosylation governing inflammatory (IL-1R1 N193) and metabolic/ferroptotic (PPARγ) signaling, broadening the disease reach of B4GALT1.\",\n      \"evidence\": \"Co-IP, PNGase F, site-directed mutagenesis, conditional/AAV knockdown mice in OA and MASLD models\",\n      \"pmids\": [\"42002123\", \"41860570\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"PPARγ glycosylation site not specified\", \"How glycosylation flips stability up (IL-1R1) versus down (PPARγ) is unexplained\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed a catalysis-independent trafficking role: B4GALT1 retains LRP5/6 in the Golgi to dampen WNT signaling, with Wntless competing for the interaction.\",\n      \"evidence\": \"Co-IP, cell surface translocation assays, and LGK974 pharmacology\",\n      \"pmids\": [\"41182165\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether retention requires galactosyltransferase activity unresolved\", \"Structural basis of B4GALT1–LRP5/6 and B4GALT1–Wntless binding unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed enzyme function is metabolically gated, with UDP-Gal availability controlling B4GALT1–SLC35A2 complex assembly.\",\n      \"evidence\": \"CRISPR knockout of GALE/GALT, NanoBiT PPI assay, and N-glycan profiling in HEK293T\",\n      \"pmids\": [\"40230451\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which UDP-Gal promotes complex formation not defined\", \"Physiological conditions under which this gating operates unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Mapped a broad regulatory network (transcriptional and post-transcriptional) positioning B4GALT1 as both an oncogenic effector and context-dependent tumor suppressor controlling chemoresistance.\",\n      \"evidence\": \"Reporter, RNAi/overexpression rescue, Co-IP, and ubiquitination assays across leukemia, prostate, and esophageal cancer models\",\n      \"pmids\": [\"23024026\", \"27516205\", \"27797721\", \"32902124\", \"40097806\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Context-dependence of oncogenic vs suppressor roles not reconciled\", \"Many links are correlative or single-lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Preprint evidence proposes B4GALT1 galactosylates TCR/CD8 to limit T-cell activation and elongates NOTCH O-glucose glycans to modulate Notch signaling, expanding its substrate repertoire to immune receptors and developmental signaling.\",\n      \"evidence\": \"CRISPR screens with AP-MS substrate ID and rescue (TCR/CD8); MS, mutagenesis, and Notch reporters (NOTCH1/3) — both preprints\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Not peer-reviewed\", \"TCR/CD8 and NOTCH substrate claims await independent confirmation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how B4GALT1 achieves substrate selectivity that produces opposite fates (stabilization vs destabilization) and how catalytic versus non-catalytic (trafficking) functions are partitioned in vivo.\",\n      \"evidence\": \"No timeline study reconciles substrate-specific outcomes with a unifying recognition or regulatory mechanism\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of substrate-specific recognition\", \"Catalysis-dependent vs catalysis-independent roles not cleanly separated\", \"Glycan-structure-to-phenotype mapping incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 1, 2, 5, 18]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [3, 4, 5, 8, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 7, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 2, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [7, 16]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [3, 8]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ST6GAL1\", \"SLC35A2\", \"LRP5\", \"LRP6\", \"IL1R1\", \"CDK11\", \"UBE2Q1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}