Affinage

GALNT2

Polypeptide N-acetylgalactosaminyltransferase 2 · UniProt Q10471

Length
571 aa
Mass
64.7 kDa
Annotated
2026-04-28
52 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALNT2 encodes polypeptide GalNAc-transferase 2 (GalNAc-T2), which catalyzes the transfer of GalNAc to serine/threonine residues in the initiating step of mucin-type O-glycosylation via a UDP-GalNAc-dependent induced-fit mechanism involving both a catalytic domain for initial site selection and a lectin domain that enhances glycan density on clustered substrates (PMID:29601100, PMID:30759204). In vivo glycoproteomics across multiple tissues identifies hundreds of non-redundant GalNAc-T2 substrates, with key validated targets including ApoC-III, ANGPTL3, PLTP, the insulin receptor, EGFR, MET, AXL, IGF1R, integrins, and viral spike proteins, through which GALNT2 regulates HDL-cholesterol and triglyceride metabolism, insulin signaling, receptor tyrosine kinase activity in multiple cancers, and antiviral innate immunity (PMID:37862385, PMID:27508872, PMID:35304331, PMID:21990321, PMID:41387548). GALNT2-mediated O-glycosylation of ANGPTL3 near its proprotein convertase cleavage site directly inhibits ANGPTL3 processing, providing a mechanistic basis for glycosylation-dependent control of lipid metabolism (PMID:32999434). Biallelic loss-of-function mutations in GALNT2 cause a congenital disorder of glycosylation (GALNT2-CDG) with metabolic and neurodevelopmental phenotypes including loss of ApoC-III glycosylation and neuronal dysfunction recapitulated in rodent models (PMID:32293671).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2011 High

    Identifying the first physiological substrates of GalNAc-T2 established that this transferase directly glycosylates ApoC-III and EGFR, linking O-glycosylation to triglyceride metabolism and receptor tyrosine kinase signaling in cancer.

    Evidence In vitro glycosylation of ApoC-III peptide with loss-of-function mutant validation; GALNT2 gain/loss-of-function in HCC cells with EGFR phosphorylation and erlotinib epistasis

    PMID:21990321 PMID:22152306

    Open questions at the time
    • No crystal structure of enzyme–ApoC-III complex
    • Direction of EGFR glycosylation effect (activating vs. inhibiting) appeared context-dependent across tissues
  2. 2012 Medium

    Demonstrating that GALNT2 O-glycosylates β1-integrin in extravillous trophoblasts extended the substrate repertoire beyond soluble apolipoproteins and RTKs to cell-adhesion receptors, showing glycosylation modulates FAK-dependent migration.

    Evidence VVA lectin pull-down for Tn antigen on β1-integrin; collagen IV adhesion and migration assays in HTR8/SVneo cells

    PMID:23117232

    Open questions at the time
    • Precise glycosylation sites on β1-integrin not mapped
    • Not replicated in other integrin-dependent cell types
  3. 2013 Medium

    Linking GALNT2 to insulin signaling via ENPP1 suppression revealed a non-canonical role beyond direct glycosylation of signaling receptors, positioning GALNT2 as a metabolic modulator in hepatocytes.

    Evidence siRNA/overexpression in HepG2 cells; Western blot of IR/IRS-1/Akt phosphorylation; ENPP1 protein-level changes

    PMID:23500900

    Open questions at the time
    • Whether GALNT2 glycosylates ENPP1 directly or acts indirectly was not resolved
    • Not independently replicated
  4. 2016 High

    Cross-species loss-of-function studies and O-glycoproteomics identified ANGPTL3 and PLTP as additional non-redundant GalNAc-T2 substrates, establishing that GALNT2 controls HDL metabolism through glycosylation of multiple lipid-regulatory proteins.

    Evidence Human homozygous LOF mutations; O-glycoproteomics in human and rodent samples; hepatic Galnt2 reconstitution rescuing PLTP activity in mice

    PMID:27508872

    Open questions at the time
    • How glycosylation of each substrate individually contributes to HDL levels not deconvolved
    • Tissue-specific substrate hierarchy not resolved
  5. 2018 High

    Structural and biophysical analysis of the F104S loss-of-function mutant revealed that GalNAc-T2 uses a UDP-GalNAc-dependent induced-fit mechanism for peptide substrate binding, explaining how a distal mutation abolishes catalysis without affecting the active site.

    Evidence Crystal structure of F104S mutant; STD-NMR showing loss of peptide binding; 19F NMR confirming conformational change; MD simulations

    PMID:29601100

    Open questions at the time
    • No structure of wild-type enzyme with bound peptide substrate
    • Mechanism of lectin domain contribution not structurally resolved
  6. 2019 High

    Domain dissection of IgA1 hinge-region glycosylation revealed that GalNAc-T2's catalytic domain selects initial glycosylation sites by sequence preference while its lectin domain expands pathway exploration, defining how a single transferase generates clustered O-glycan patterns.

    Evidence LC-MS glycosylation assay with recombinant GalNAc-T2 and domain-specific mutants on IgA1 hinge peptide

    PMID:30759204

    Open questions at the time
    • Whether this dual-domain mechanism applies to all multi-site substrates in vivo is untested
    • No structural basis for lectin domain–GalNAc recognition on the same substrate
  7. 2020 High

    Showing that GALNT2-mediated O-glycosylation of ANGPTL3 near its proprotein convertase cleavage site blocks proteolytic processing provided the first mechanistic explanation for how site-specific glycosylation controls the activity of a lipid-regulatory protein.

    Evidence Reciprocal Galnt2 overexpression/knockdown in primary hepatocytes and in vivo; epistasis with PC inhibitor; Western blot of ANGPTL3 cleavage

    PMID:32999434

    Open questions at the time
    • Exact glycosylation site(s) near the PC cleavage site not mapped at single-residue resolution
    • Whether other GalNAc-T isoenzymes can partially compensate not tested
  8. 2020 High

    Clinical and animal-model characterization of GALNT2-CDG established that biallelic GALNT2 loss causes a congenital disorder of glycosylation with both metabolic (lipid) and neurodevelopmental phenotypes, demonstrating non-redundant substrate requirements across tissues.

    Evidence O-glycoproteomics in GALNT2-deficient patients; mouse and rat KO models with behavioral phenotyping

    PMID:32293671

    Open questions at the time
    • Critical neuronal substrates responsible for neurodevelopmental phenotype not identified
    • Whether CDG phenotype severity correlates with residual enzymatic activity unknown
  9. 2022 High

    Identification of the insulin receptor as a direct GalNAc-T2 substrate in vivo, combined with metabolic phenotyping of Galnt2-null mice, extended GALNT2's metabolic role from lipid metabolism to whole-body energy homeostasis.

    Evidence Galnt2-/- mouse model; mass spectrometry glycoproteomics identifying IR glycosylation sites; metabolic phenotyping of energy expenditure and substrate utilization

    PMID:35304331

    Open questions at the time
    • How IR glycosylation mechanistically alters insulin signaling kinetics not resolved
    • Relative contribution of IR glycosylation vs. ENPP1 suppression to insulin sensitivity unclear
  10. 2022 Medium

    Identification of AXL and ITGA5 as glycosylation substrates in colorectal and lung cancers respectively broadened the oncogenic receptor repertoire beyond EGFR and MET, showing GALNT2 stabilizes AXL via proteasome-dependent mechanisms.

    Evidence CRISPR-KO and siRNA epistasis for AXL in CRC; lectin pull-down for ITGA5 in NSCLC; in vivo metastasis models

    PMID:36058918 PMID:36409270

    Open questions at the time
    • Precise glycosylation sites on AXL and ITGA5 not mapped
    • Cancer-type specificity of substrate preference not systematically addressed
  11. 2023 High

    A comprehensive in vivo O-glycoproteomics atlas across nine tissues in Galnt2-null mice defined the non-redundant contribution of GalNAc-T2 to 595 glycoproteins, revealing tissue-specific regulation partly driven by differential GalNAc-T isoenzyme expression.

    Evidence Quantitative glycoproteomics with chemical and enzymatic O-glycosite cleavage and HCD-triggered ETD/HCD MS across nine mouse tissues

    PMID:37862385

    Open questions at the time
    • Functional consequences of most identified glycosite losses not individually tested
    • Human tissue-level atlas not yet generated
  12. 2023 High

    Demonstrating that the GWAS SNP rs4846913 drives allele-specific CEBPB binding at the GALNT2 locus connected common genetic variation in HDL-C to transcriptional regulation of GALNT2 in hepatocytes.

    Evidence EMSA, ChIP, luciferase reporters, allelic expression imbalance, and eQTL in human hepatocytes

    PMID:26637976

    Open questions at the time
    • Whether other transcription factors co-regulate GALNT2 at this locus not fully explored
    • Effect size of this variant on downstream substrate glycosylation not quantified
  13. 2025 High

    Identification of GALNT2 as an interferon-stimulated gene that restricts coronavirus and influenza replication by O-glycosylating viral spike protein at S810/S813 to block proteolytic processing and virus-cell fusion revealed a direct antiviral effector function.

    Evidence GALNT2 KO/OE viral replication assays; site-directed mutagenesis of spike S810/S813; scRNA-seq in COVID-19 patients; human LOF variant association with hospitalization

    PMID:41387548

    Open questions at the time
    • Whether GALNT2 restricts other enveloped viruses beyond coronaviruses and influenza A untested
    • Structural basis for spike protein glycosylation by GalNAc-T2 not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of critical neuronal substrates responsible for GALNT2-CDG neurodevelopmental phenotypes, the structural basis for full-length enzyme–substrate recognition including lectin domain engagement, and whether tissue-specific or disease-specific therapeutic modulation of GALNT2 activity is feasible.
  • Neuronal substrates driving seizures and behavioral deficits in GALNT2-CDG remain unidentified
  • No full-length GalNAc-T2 structure with peptide substrate bound
  • Therapeutic window for GALNT2 modulation not defined given broad substrate repertoire

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016740 transferase activity 8
Localization
GO:0005794 Golgi apparatus 4
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-392499 Metabolism of proteins 7 R-HSA-1643685 Disease 6 R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 1
Partners
ANGPTL3APOC3AXLEGFRIGF1RINSRMETPLTP

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 GALNT2 (ppGalNAc-T2) glycosylates apolipoprotein C-III (apoC-III) at a specific peptide substrate site; an apoC-III-based peptide was confirmed as a direct substrate for ppGalNAc-T2 in vitro, and the loss-of-function mutant enzyme showed impaired glycosylation of this substrate. Reduced sialylation of apoC-III glycans (by neuraminidase treatment) decreased apoC-III's ability to inhibit lipoprotein lipase (LPL), linking GALNT2-mediated O-glycosylation to postprandial triglyceride clearance. In vitro glycosylation assay with synthetic apoC-III peptide substrate; neuraminidase treatment + LPL inhibition assay; plasma glycoproteomics in human carriers Cell metabolism High 22152306
2011 GALNT2 modifies O-glycans on EGFR in hepatocellular carcinoma cells; restoring GALNT2 expression altered the O-glycan status of EGFR, reducing EGF-induced EGFR signaling and downstream malignant behaviors. EGFR inhibition (erlotinib) phenocopied GALNT2 restoration, establishing EGFR as the critical mediator of GALNT2's tumor-suppressive effects in HCC. Overexpression/knockdown of GALNT2 in HCC cells + EGF stimulation assays; Western blotting of EGFR phosphorylation; erlotinib epistasis; in vivo xenograft Cancer research High 21990321
2013 GALNT2 modulates ENPP1 expression in human liver (HepG2) cells: GALNT2 downregulation increased ENPP1 protein levels while GALNT2 overexpression reduced them. Because ENPP1 inhibits insulin signaling, GALNT2 knockdown reduced insulin-stimulated phosphorylation of IR, IRS-1, and Akt and impaired PEPCK suppression, identifying GALNT2 as a positive modulator of insulin signaling via ENPP1. RNA pulldown + mass spectrometry to identify ENPP1 3'UTR binding; siRNA knockdown and overexpression of GALNT2 in HepG2 cells; Western blot of IRS-1/Akt phosphorylation; ELISA for IR autophosphorylation; RT-PCR for PEPCK Biochimica et biophysica acta Medium 23500900
2014 GALNT2 modifies O-glycans on EGFR in oral squamous cell carcinoma (OSCC) cells, enhancing EGF-induced EGFR and AKT phosphorylation and promoting cell migration and invasion. VVA lectin pull-down confirmed altered Tn antigen (GalNAc-Ser/Thr) levels on EGFR upon GALNT2 modulation. GALNT2 overexpression/knockdown in SAS cells; VVA lectin pulldown for O-glycan detection on EGFR; Western blot of pEGFR/pAKT; transwell migration/invasion assays Oral oncology Medium 24582885
2016 GALNT2 loss-of-function in humans, nonhuman primates, and rodents lowers HDL-C. O-glycoproteomics of a human GALNT2-deficient subject identified ANGPTL3 and ApoC-III as direct GalNAc-T2 substrates; in rodents, phospholipid transfer protein (PLTP) was additionally identified. Hepatic Galnt2 reconstitution in mice rescued plasma PLTP activity, establishing GALNT2 as a direct modulator of HDL metabolism through glycosylation of PLTP, ANGPTL3, and ApoC-III. Human genetics (homozygous LOF mutations); O-glycoproteomics in human and rodent GALNT2-deficient samples; hepatic Galnt2 reconstitution in mice; plasma PLTP activity assay Cell metabolism High 27508872
2016 GALNT2 suppresses malignant phenotypes in gastric adenocarcinoma by O-glycosylating MET (hepatocyte growth factor receptor); GALNT2 knockdown enhanced MET phosphorylation and decreased Tn antigen expression on MET. MET inhibitor PHA665752 rescued the malignant phenotypes caused by GALNT2 knockdown, establishing MET as a functional downstream target. GALNT2 knockdown in GCA cell lines; Western blot of p-MET and Tn antigen; PHA665752 epistasis; in vivo metastasis assay Oncotarget Medium 26848976
2018 Structural and NMR analysis of the GalNAc-T2 F104S loss-of-function mutant revealed that this residue (not at the active site) is required for peptide substrate binding. The WT enzyme adopts an induced-fit active conformation only in the presence of UDP-GalNAc (donor sugar), and F104S prevents this conformational transition. STD-NMR confirmed loss of peptide binding in the mutant; MD simulations showed disordered flexible loop in F104S; 19F NMR confirmed UDP-GalNAc-dependent conformational change. Crystal structure of F104S mutant bound to UDP-GalNAc; STD-NMR; 19F NMR; molecular dynamics simulations Chemistry (Weinheim an der Bergstrasse, Germany) High 29601100
2018 GALNT2 modifies O-glycans on EGFR in gastric adenocarcinoma cells; GALNT2 knockdown enhanced EGFR phosphorylation and Akt activation while decreasing Tn antigen on EGFR. Gefitinib (EGFR inhibitor) and MK2206 (Akt inhibitor) reversed the pro-migratory/invasive effects of GALNT2 knockdown. siRNA knockdown; Western blot of pEGFR, pAkt, Tn antigen; Gefitinib and MK2206 epistasis assays; migration/invasion assays American journal of cancer research Medium 30323967
2019 GalNAc-T2 uses both its catalytic domain and lectin domain to glycosylate the IgA1 hinge region in a semi-ordered, multi-step process: the catalytic domain selects four initial glycosylation sites based on amino-acid sequence, while the lectin domain enhances glycan density by expanding pathway exploration for subsequent site selection. This defines a mechanism by which a single GalNAc-T isoenzyme controls clustered O-glycosylation patterns. LC-MS glycosylation assay of IgA1 hinge-region peptide using recombinant GalNAc-T2; domain-specific mutant analysis (catalytic vs. lectin domain contributions) Glycobiology High 30759204
2019 GALNT2 modifies O-glycans on EGFR in glioma cells; GALNT2 knockdown decreased Tn antigen on EGFR and reduced phosphorylated EGFR, thereby suppressing the EGFR/PI3K/Akt/mTOR pathway and downstream effectors (CDK4, cyclinD1, MMP2, MMP9, p21). Lectin pull-down assays confirmed altered O-glycosylation of EGFR. GALNT2 knockdown/overexpression in glioma cell lines; lectin pull-down assay for Tn antigen on EGFR; Western blot of EGFR/PI3K/Akt/mTOR pathway; orthotopic xenograft in nude mice Clinical science (London, England : 1979) Medium 31076460
2019 GALNT2 promotes adipogenesis and enhances insulin signaling (IR, IRS1, AKT phosphorylation) in mouse 3T3-L1 preadipocytes, an effect associated with reduced ENPP1 expression; this effect is reversed during late-stage adipocyte maturation, suggesting GALNT2 acts as a modulator of the preadipocyte-to-adipocyte transition. Stable GALNT2 overexpressing 3T3-L1 preadipocytes; Oil Red-O staining, fluorimetric triglyceride assay; confocal microscopy of lipid droplets; RT-PCR of 72 adipogenesis genes; Western blot of IR/IRS1/JNK/AKT phosphorylation International journal of obesity (2005) Medium 31040393
2020 GALNT2-mediated O-glycosylation of ANGPTL3 near its proprotein convertase (PC) cleavage site inhibits PC-mediated cleavage of ANGPTL3 in primary hepatocytes and in vivo in mice. Galnt2 overexpression blocked endogenous Angptl3 cleavage; Galnt2 suppression dramatically increased cleavage; PC inhibition phenocopied Galnt2 overexpression. Galnt2 overexpression and knockdown in primary mouse hepatocytes and in vivo; Western blot of Angptl3 cleavage products; PC inhibitor co-treatment Scientific reports High 32999434
2020 GALNT2-CDG patients show loss of O-glycosylation of apolipoprotein C-III, confirmed as a non-redundant substrate for GALNT2. Rodent (mouse and rat) models of GALNT2-CDG recapitulated metabolic and neurodevelopmental phenotypes, demonstrating that multiple non-redundant protein substrates of GALNT2 exist across tissues including brain. O-glycoproteomics in human GALNT2-deficient patients; mouse and rat knockout models with behavioral testing (cerebellar motor, sociability, sensory integration); ApoC-III glycosylation analysis Brain : a journal of neurology High 32293671
2021 Computational docking analysis identified specific enzyme residues (R362, K363, Q364, H365, W331 for -1 position; K281 and K363 for +1 position) that determine the peptide substrate preferences of GalNAc-T2, explaining why proline, serine, threonine, and alanine at the -1 position are preferred glycosylatable substrates. Rosetta Monte Carlo-minimization flexible docking of 361 peptide substrates against GalNAc-T2 crystal structure; ROC-AUC validation against experimental glycosylation data ACS catalysis Low 34322281
2022 GALNT2 modifies O-glycans on ITGA5 (integrin alpha-5) in NSCLC cells, affecting activation of PI3K/Akt and MAPK/ERK pathways and driving cell proliferation, migration, and invasion. miR-30d was identified as a negative regulator of GALNT2 expression. GALNT2 knockdown/overexpression in NSCLC cells; high-throughput sequencing; Western blot of PI3K/Akt and MAPK/ERK pathways; in vivo xenograft; luciferase assay for miR-30d targeting Cellular & molecular biology letters Medium 36058918
2022 GALNT2 modifies O-glycans on AXL receptor tyrosine kinase in colorectal cancer cells and stabilizes AXL protein levels via the proteasome-dependent pathway; siRNA knockdown of AXL significantly reversed GALNT2-promoted invasiveness, establishing AXL as a functional downstream target of GALNT2 O-glycosylation. GALNT2 overexpression/siRNA knockdown/CRISPR-Cas9 knockout; AXL siRNA epistasis; proteasome inhibitor assays; peritoneal metastasis in vivo model Molecular oncology Medium 36409270
2022 The insulin receptor is a novel substrate of GalNAc-T2; Galnt2-/- mice exhibit decreased adiposity, altered insulin signaling, and a shift in energy substrate utilization, demonstrating that GALNT2-mediated O-glycosylation of the insulin receptor contributes to energy homeostasis beyond lipid metabolism. Galnt2-/- mouse model; mass spectrometry-based glycoproteomics identifying insulin receptor as substrate; metabolic phenotyping (energy expenditure, substrate utilization); insulin signaling assays Molecular metabolism High 35304331
2012 GALNT2 is expressed in extravillous trophoblasts (EVT) and increases Tn antigen (GalNAc-Ser/Thr) O-glycosylation on β1-integrin. Overexpression of GALNT2 in HTR8/SVneo cells enhanced cell-collagen IV adhesion but suppressed migration and invasion by reducing focal adhesion kinase (FAK) phosphorylation downstream of β1-integrin. GALNT2 overexpression in HTR8/SVneo EVT cells; VVA lectin pull-down for Tn antigen on β1-integrin; collagen IV adhesion assay; migration/invasion assays; Western blot of p-FAK Placenta Medium 23117232
2023 Quantitative in vivo O-glycoproteomics in Galnt2-null mice across nine tissues identified a network of glycoproteins lacking GalNAc-T2-specific O-glycans, defining 2,154 total O-glycosites from 595 glycoproteins. This atlas revealed tissue-specific regulation of O-glycosites partly driven by differential Galnt isoenzyme expression and established the non-redundant contribution of GalNAc-T2 to the in vivo O-glycoproteome. Chemical and enzymatic O-glycosite cleavage; HCD-triggered ETD/HCD mass spectrometry; quantitative glycoproteomics and proteomics across nine mouse tissues; Galnt2-null mouse model Proceedings of the National Academy of Sciences of the United States of America High 37862385
2023 GALNT2 rs4846913 variant drives allele-specific CEBPB transcription factor binding at the GALNT2 locus, influencing GALNT2 hepatic expression levels; GWAS SNPs associated with reduced HDL-C correlate with lower GALNT2 expression, confirmed by EMSA, ChIP, luciferase assay, allelic-expression-imbalance, and eQTL analyses in human hepatocytes. Luciferase reporter assays in HepG2/Huh-7 cells; EMSA; ChIP-seq allelic imbalance; allelic expression imbalance in primary human hepatocytes; eQTL analysis American journal of human genetics High 26637976
2025 GALNT2 is an interferon-stimulated gene that restricts replication of coronaviruses and influenza A viruses. Mechanistically, GALNT2-dependent O-linked glycosylation at serine residues 810/813 of the viral SARS-CoV-2 spike protein impairs proteolytic processing of the viral glycoprotein and blocks virus-cell fusion. Individuals with GALNT2 LOF variants had elevated risk of COVID-19 hospitalization. Transcriptomic profiling in IFNAR-/- mice + COVID-19 patient scRNA-seq; in vitro and in vivo viral replication assays with GALNT2 KO/OE; site-directed mutagenesis of spike S810/S813; viral glycoprotein processing assays Nature microbiology High 41387548
2024 Pancreatic-specific GalNAc-T2 overexpression in mice causes dose-dependent loss of acinar mass, pancreatic steatosis (heterozygous), and lethal complete pancreatic loss with adipocyte transdifferentiation from pancreatic cells (homozygous). PNA lectin enrichment and mass spectrometry identified additional O-glycosylation sites created by GalNAc-T2 overexpression. Conditional transgenic mouse model with pancreas-specific GalNAc-T2 overexpression; reporter gene lineage tracing; PNA lectin enrichment + MS proteome analysis Scientific reports Medium 39613794
2024 Isoferulic acid (IFA) directly interacts with GALNT2 in gastric epithelial cells (confirmed by Co-IP, molecular docking, and fluorescence spectroscopy) and inhibits alcohol-induced downregulation of GALNT2 activity, thereby promoting mucin synthesis and protecting against gastric mucosal injury. Co-immunoprecipitation; molecular docking; fluorescence spectroscopy; in vitro cell viability assays; in vivo rat gastric mucosal injury model; gastric hexosamine and mucus level quantification Nutrients Medium 38999895
2025 Galnt2-expressing glucose-inhibited neurons in the ventromedial hypothalamus (VMH) function as a molecular brake on hypoglycemia counterregulation; conditional ablation studies defined a VMH→PVH→LPGi→liver neurocircuit through which Galnt2-positive neurons detect neuroglycopenia and drive hepatic glucose production via intrahepatic sympathetic activation. Viral tracing; single-nucleus RNA sequencing; Cre-dependent conditional ablation; in vivo glucose monitoring; intrahepatic sympathetic nerve recording Cell metabolism Medium 41092902
2024 Neuron-specific conditional Galnt2 knockout mice exhibit behavioral deficits across locomotion, motor coordination, sociability, learning, memory, and spontaneous seizures, recapitulating GALNT2-CDG neurological features. Glycoproteomics of cortical synaptosomes identified disrupted O-glycosylation at specific sites on candidate neuronal glycoproteins, demonstrating a non-redundant role of GALNT2 in the cortical synaptosomal O-glycoproteome. Pan-neuronal conditional Galnt2 knockout mice; behavioral battery (open field, rotarod, social interaction, Morris water maze, EEG); synaptosomal glycoproteomics by mass spectrometry bioRxivpreprint Medium bio_10.1101_2024.09.30.615951
2023 In a CRISPR screen using human midline assembloids, GALNT2 knockdown in floor plate cells impaired floor plate-mediated guidance of commissural axons, identifying a human-specific role for GALNT2 O-glycosylation in axon guidance that is evolutionarily divergent from mouse. Arrayed CRISPR knockout screen in human floor plate organoids assembled with spinal cord organoids (midline assembloids); commissural axon guidance assay bioRxivpreprint Low bio_10.1101_2024.06.26.600229
2023 GALNT2 promotes glioblastoma stem cell (GSC) self-renewal by sustaining CD44 expression. STAT3 directly activates GALNT2 transcription by binding the GALNT2 promoter (ChIP/reporter assay). Targeting GALNT2 with a small-molecule inhibitor suppressed GSC self-maintenance in vitro and in vivo. GALNT2 knockdown in GSCs; STAT3 ChIP and luciferase reporter assay for GALNT2 promoter binding; sphere formation and invasion assays; in vivo orthotopic xenograft; GALNT2 inhibitor treatment Aging Medium 37000153
2023 GALNT2 modifies O-glycans on IGF1R in radioresistant NSCLC cells (confirmed by lectin pull-down); GALNT2 knockdown improved radiosensitivity by inducing apoptosis, an effect enhanced by IGF1R inhibition. miR-30a-5p was identified as an upstream negative regulator of GALNT2 by luciferase reporter assay. Fractionated irradiation to generate radioresistant cell models; transcriptomic, proteomic, and glycomic analyses; lectin pull-down for O-glycans on IGF1R; in vitro and in vivo radiosensitivity assays; miRNA array + luciferase reporter Cell biology and toxicology Medium 37597090
2024 miR-139-5p directly targets the 3'UTR of GALNT2 (confirmed by dual luciferase reporter assay) and negatively regulates GALNT2 expression in clear cell renal cell carcinoma. GALNT2 promotes cell proliferation by suppressing LATS2 phosphorylation and preventing downstream YAP phosphorylation/degradation; LATS2 knockdown rescued the anti-proliferative effect of GALNT2 deficiency. Dual luciferase reporter assay for miR-139-5p/GALNT2 3'UTR interaction; shRNA knockdown of GALNT2; Western blot of p-LATS2, p-YAP; LATS2 knockdown epistasis; cell proliferation assays Discover oncology Medium 38478152

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents. Cell metabolism 114 27508872
2011 Mucin glycosylating enzyme GALNT2 regulates the malignant character of hepatocellular carcinoma by modifying the EGF receptor. Cancer research 98 21990321
2011 Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man. Cell metabolism 89 22152306
2014 GALNT2 enhances migration and invasion of oral squamous cell carcinoma by regulating EGFR glycosylation and activity. Oral oncology 85 24582885
2020 Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Brain : a journal of neurology 64 32293671
2014 A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease. PloS one 50 25084356
2015 Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated with High-Density Lipoprotein Cholesterol. American journal of human genetics 49 26637976
2019 Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis. Clinical science (London, England : 1979) 43 31076460
2016 Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation. Oncotarget 40 26848976
2022 The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer. Cellular & molecular biology letters 33 36058918
2013 GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia. PloS one 32 23894607
2021 GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma. Life sciences 28 33785338
2018 The O-glycosylating enzyme GALNT2 suppresses the malignancy of gastric adenocarcinoma by reducing EGFR activities. American journal of cancer research 28 30323967
2016 Association between the DOCK7, PCSK9 and GALNT2 Gene Polymorphisms and Serum Lipid levels. Scientific reports 28 26744084
2013 Role of GALNT2 in the modulation of ENPP1 expression, and insulin signaling and action: GALNT2: a novel modulator of insulin signaling. Biochimica et biophysica acta 27 23500900
2011 Association of the GALNT2 gene polymorphisms and several environmental factors with serum lipid levels in the Mulao and Han populations. Lipids in health and disease 25 21933382
2012 Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion. Placenta 24 23117232
2022 GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL. Molecular oncology 20 36409270
2020 GALNT2 regulates ANGPTL3 cleavage in cells and in vivo of mice. Scientific reports 20 32999434
2018 Paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice. European journal of pharmacology 19 30096295
2015 Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia. Journal of cellular and molecular medicine 19 26493351
2019 GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling. International journal of obesity (2005) 18 31040393
2016 Looking beyond GWAS: allele-specific transcription factor binding drives the association of GALNT2 to HDL-C plasma levels. Lipids in health and disease 17 26817450
2022 Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis. International journal of molecular sciences 16 35055114
2018 Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. Chemistry (Weinheim an der Bergstrasse, Germany) 16 29601100
2023 Quantitative mapping of the in vivo O-GalNAc glycoproteome in mouse tissues identifies GalNAc-T2 O-glycosites in metabolic disorder. Proceedings of the National Academy of Sciences of the United States of America 14 37862385
2016 GALNT2 effect on HDL-cholesterol and triglycerides levels in humans: Evidence of pleiotropy? Nutrition, metabolism, and cardiovascular diseases : NMCD 14 28153384
2015 Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 genes in healthy Roma and Hungarian populations. Pathology oncology research : POR 14 25573592
2020 Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 12 33152927
2019 IgA1 hinge-region clustered glycan fidelity is established early during semi-ordered glycosylation by GalNAc-T2. Glycobiology 12 30759204
2022 A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis. Molecular metabolism 11 35304331
2015 Gene environment interaction of GALNT2 and APOE gene with hypertension in the Chinese Han Population. Bio-medical materials and engineering 11 26405973
2011 Production of N-acetylgalactosaminyl-transferase 2 (GalNAc-T2) fused with secretory signal Igκ in insect cells. Protein expression and purification 10 22033505
2021 Structural basis for peptide substrate specificities of glycosyltransferase GalNAc-T2. ACS catalysis 9 34322281
2023 Apolipoprotein-CIII O-Glycosylation, a Link between GALNT2 and Plasma Lipids. International journal of molecular sciences 8 37834292
2020 GALNT2 Gene Variant rs4846914 Is Associated with Insulin and Insulin Resistance Depending on BMI in PCOS Patients: a Case-Control Study. Reproductive sciences (Thousand Oaks, Calif.) 8 33171515
2021 Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus. Frontiers in endocrinology 7 34267728
2023 GALNT2 sustains glioma stem cells by promoting CD44 expression. Aging 6 37000153
2023 GALNT2, an O-glycosylating enzyme, is a critical regulator of radioresistance of non-small cell lung cancer: evidence from an integrated multi-omics analysis. Cell biology and toxicology 6 37597090
2010 A polymorphism in the GALNT2 gene and ovarian cancer risk in four population based case-control studies. International journal of molecular epidemiology and genetics 5 21532840
2025 Exploring the combined roles of GALNT1 and GALNT2 in hepatocellular carcinoma malignancy and EGFR modulation. Discover oncology 4 40095226
2024 GalNT2-mediated O-glycosylation affects pancreas development and function in mice. Scientific reports 4 39613794
2021 Morphological and molecular characterization of GALNT2-mediated adipogenesis. International journal of obesity (2005) 3 33658684
2025 Galnt2 neurons in the ventromedial hypothalamus counterregulate hypoglycemia via a brain-liver neurocircuit. Cell metabolism 2 41092902
2024 Gastroprotective Effect of Isoferulic Acid Derived from Foxtail Millet Bran against Ethanol-Induced Gastric Mucosal Injury by Enhancing GALNT2 Enzyme Activity. Nutrients 2 38999895
2023 Leveraging Genetics to Address the Role of GALNT2 on Atherogenic Dyslipidemia. Advanced biology 2 36861373
2025 Interferon-stimulated gene GALNT2 restricts respiratory virus infections. Nature microbiology 1 41387548
2024 GALNT2 targeted by miR-139-5p promotes proliferation of clear cell renal cell carcinoma via inhibition of LATS2 activation. Discover oncology 1 38478152
2023 Role of a novel mouse mutant of the Galnt2 gene in otitis media. Frontiers in neurology 1 36874359
2024 GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes. Acta diabetologica 0 38627282
2023 Corrigendum: Role of a novel mouse mutant of the Galnt2 gene in otitis media. Frontiers in neurology 0 37885477
2022 Effects of RNA Modification "Writers" of GALNT2 on the Tumor Microenvironment in Cervical Squamous Cell Carcinoma. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 0 36374960