Affinage

EXT2

Exostosin-2 · UniProt Q93063

Length
718 aa
Mass
82.3 kDa
Annotated
2026-06-09
100 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EXT2 is a Golgi-localized glycosyltransferase that, in obligate partnership with EXT1, catalyzes the polymerization of heparan sulfate (HS) chains required for normal development and skeletal patterning (PMID:9756849, PMID:10639137, PMID:12907685). EXT1 and EXT2 associate into a hetero-oligomeric complex whose formation relocates both proteins from the ER to the Golgi and confers glycosyltransferase activity far exceeding either protein alone; coexpression rather than mixing of separately produced subunits is required for this stimulation (PMID:10639137, PMID:11256613, PMID:12907685). Cryo-EM of the human EXT1-EXT2 heterodimer resolves a tightly packed assembly of four glycosyltransferase domains and, together with mutational analysis, indicates that EXT1 carries both GlcA and GlcNAc transferase activities while EXT2 contributes predominantly GlcNAc transferase activity, with chain elongation proceeding nonprocessively (PMID:36402845). Beyond elongation, EXT2 expression level controls the amount and N-glycosylation of NDST1 and physically associates with it, thereby coupling chain polymerization to HS sulfation in a GAGosome model (PMID:18337501). The HS produced by this machinery is selectively required for FGF and Wnt — but not Hedgehog — signaling during development, governing axon pathfinding, fin/limb outgrowth, and chondrocyte/osteoblast differentiation (PMID:15603738, PMID:16221725, PMID:21892940). Genetically, EXT2 loss is dose-sensitive: homozygous loss in mice abolishes HS synthesis and blocks gastrulation, whereas heterozygosity or combined Ext1/Ext2 reduction causes exostoses, establishing haploinsufficiency as the basis of hereditary multiple exostoses (PMID:16236767, PMID:21310272). Distinct hypomorphic missense mutations cause an autosomal recessive seizures-scoliosis-macrocephaly syndrome without exostoses (PMID:26246518). A non-canonical metabolic role in which EXT2 depletion alters the SAM/transsulfuration pathway and triggers ferroptosis has been described in glioblastoma cells (PMID:40234611).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Establishing that EXT2 is itself an enzyme answered whether the gene encodes a catalytic component of HS biosynthesis rather than a regulator.

    Evidence Protein purification from bovine serum with recombinant expression and in vitro glycosyltransferase assays

    PMID:9756849

    Open questions at the time
    • Did not address whether EXT2 acts alone or requires a partner in cells
    • Relative contribution of GlcA vs GlcNAc transferase activity unresolved
  2. 2000 High

    Demonstrating that EXT1 and EXT2 form a Golgi-localized complex with synergistic activity explained why EXT2 alone has negligible activity and where HS polymerization occurs.

    Evidence In vivo/in vitro glycosyltransferase assays in EXT1-deficient cells, co-IP, subcellular fractionation, and yeast reconstitution

    PMID:10639137 PMID:10679296 PMID:11256613

    Open questions at the time
    • Stoichiometry and architecture of the complex not defined
    • Catalytic division of labor between subunits not resolved at this stage
  3. 2003 High

    Reconstituting HS polymerization with soluble co-expressed EXT1/EXT2 on a core protein established the minimal requirements for chain assembly.

    Evidence In vitro polymerization assay with co-transfection-derived soluble enzymes, glypican-1 acceptor, and radiolabeled sugar donors

    PMID:12907685

    Open questions at the time
    • Required hydrophobic aglycon implies acceptor constraints not mechanistically explained
    • Single lab
  4. 2002 Medium

    In vivo overexpression linked EXT2 dosage to HS output and bone formation and revealed coupled regulation of EXT1 expression.

    Evidence Chondrocyte-specific EXT2 transgenic mice with histology, micro-CT, and HS immunostaining

    PMID:11944914

    Open questions at the time
    • Mechanism of EXT1 upregulation upon EXT2 overexpression unknown
    • Single lab
  5. 2005 High

    Mouse knockouts defined the dose-dependent phenotypic consequences, separating embryonic-lethal complete loss from exostosis-causing haploinsufficiency.

    Evidence Ext2-null and Ext2+/- mice with biochemical HS assays, skeletal histology, and Hedgehog epistasis; later compound Ext1/Ext2 heterozygotes

    PMID:16236767 PMID:21310272

    Open questions at the time
    • Cell-autonomous vs non-autonomous origin of exostoses not fully resolved
    • Threshold of HS loss triggering exostosis incompletely quantified
  6. 2005 High

    Zebrafish genetics placed EXT2-dependent HS upstream of specific signaling pathways, defining its developmental function in axon guidance and limb outgrowth.

    Evidence Positional cloning of dackel, biochemical HS quantification, epistasis with Robo2 and Fgf10, and differential Fgf ligand rescue

    PMID:15603738 PMID:16221725

    Open questions at the time
    • Molecular basis for ligand selectivity (Fgf10 vs Fgf4) not defined
    • Direct HS-ligand binding not measured
  7. 2007 High

    Loss- and gain-of-function studies tied EXT2 specifically to HS chain length and confirmed a disease truncation abolishes its elongation-enhancing role.

    Evidence siRNA, stable overexpression, gel-filtration chain-length analysis, and EXT2-Y419X truncation mutagenesis in HEK293 cells

    PMID:17761672

    Open questions at the time
    • Step at which EXT2 controls length (initiation vs elongation rate) not resolved
  8. 2008 Medium

    Discovering that EXT2 controls NDST1 levels and N-glycosylation connected chain polymerization to sulfation, supporting a coordinated GAGosome.

    Evidence Overexpression in HEK293, transgenic mouse heart, NDST activity assays, and co-IP

    PMID:18337501

    Open questions at the time
    • EXT2-NDST1 interaction supported by co-IP but not structurally validated
    • Direct vs indirect control of NDST1 stability unclear
  9. 2014 Medium

    Defining the differentiation steps and disease alleles clarified how EXT2 loss produces exostoses and established the molecular basis of haploinsufficiency.

    Evidence Zebrafish null differentiation marker analysis, patient splice-mutation NMD analysis, and recessive missense hypomorph characterization

    PMID:24628984 PMID:24728384 PMID:26246518

    Open questions at the time
    • Link between UPR/osterix-xbp1 branch and exostosis pathogenesis remains correlative
    • Genotype-phenotype basis for distinct recessive syndrome vs HME not fully explained
  10. 2016 Medium

    Identifying translational control of EXT2 revealed a layer of post-transcriptional regulation governing enzyme abundance.

    Evidence let-7b miRNA mimics/inhibitors, reporter assays, and polyamine treatment with translation readouts

    PMID:27650265

    Open questions at the time
    • Physiological contexts where this regulation operates not established
    • Single lab
  11. 2022 High

    The cryo-EM structure defined the architecture of the EXT1-EXT2 heterodimer and assigned catalytic roles to each subunit.

    Evidence Cryo-EM structure with in vitro glycosyltransferase assays and in cellulo mutational analysis

    PMID:36402845

    Open questions at the time
    • Structural basis of nonprocessivity and substrate translocation not fully resolved
    • Conformational dynamics during catalysis not captured
  12. 2025 Medium

    A non-canonical metabolic function was uncovered, linking EXT2 to redox/transsulfuration metabolism and ferroptosis independent of HS synthesis.

    Evidence RNAi, untargeted/targeted metabolomics, lipid peroxidation assays, and tumor models in glioblastoma

    PMID:40234611

    Open questions at the time
    • Direct molecular link between EXT2 and SAM/transsulfuration enzymes not identified
    • Whether this role depends on glycosyltransferase activity unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EXT2 mechanistically couples its catalytic, sulfation-regulatory, and metabolic roles into a unified function remains unresolved.
  • No structural model of EXT2-NDST1 or a complete GAGosome
  • Molecular basis for FGF/Wnt vs Hedgehog HS specificity unknown
  • Mechanism connecting HS biosynthesis to ferroptosis/transsulfuration not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005794 Golgi apparatus 2 GO:0005783 endoplasmic reticulum 1
Partners
EXT1NDST1
Complex memberships
EXT1-EXT2 heparan sulfate polymerase complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 EXT2 encodes a glycosyltransferase with both D-glucuronyltransferase (GlcA transferase) and N-acetyl-D-glucosaminyltransferase (GlcNAc transferase) activities required for heparan sulfate chain elongation, as demonstrated by purification of EXT2 protein from bovine serum and recombinant expression assays. Protein purification from bovine serum, recombinant expression and in vitro glycosyltransferase activity assays The Journal of biological chemistry High 9756849
2000 EXT1 and EXT2 form a hetero-oligomeric complex in vivo that relocates both proteins from the ER to the Golgi apparatus; this Golgi-localized EXT1/EXT2 complex has substantially higher glycosyltransferase activity than either protein alone, and EXT2 alone has negligible glycosyltransferase activity in the absence of EXT1. In vivo and in vitro glycosyltransferase assays using an EXT1-deficient cell line, co-immunoprecipitation, subcellular fractionation and localization studies Proceedings of the National Academy of Sciences of the United States of America High 10639137
2000 EXT1 and EXT2 each individually catalyze both GlcA and GlcNAc transferase reactions when expressed in yeast (which lacks endogenous heparan sulfate), but coexpression — not mixing of separately expressed proteins — yields hetero-oligomeric complexes with augmented activity; this stimulation does not require the membrane-bound state. Recombinant expression in yeast (Saccharomyces cerevisiae) and mammalian cells, in vitro glycosyltransferase assays, co-immunoprecipitation EMBO reports High 11256613
2000 EXT1 and EXT2 associate to form homo- and hetero-oligomers in vivo and both proteins localize to the Golgi apparatus, irrespective of HME-linked missense mutations (EXT1 R340C; EXT2 D227N). Co-immunoprecipitation with specific antibodies, immunocytochemistry in COS-7 cells Biochemical and biophysical research communications Medium 10679296
2003 Co-expression (not mixing) of recombinant soluble EXT1 and EXT2 achieves in vitro heparan sulfate chain polymerization on glypican-1 core protein or a synthetic linkage-region analog; neither individually expressed EXT1 or EXT2 alone nor acceptor substrates lacking a hydrophobic aglycon support polymerization, indicating that both the EXT1-EXT2 interaction and core protein moieties are required. In vitro HS polymerization assay using co-transfection-derived soluble recombinant EXT1/EXT2 with UDP-[3H]GlcNAc and UDP-GlcUA, gel filtration sizing The Journal of biological chemistry High 12907685
2005 Homozygous loss of Ext2 in mice abolishes heparan sulfate synthesis, causing growth arrest and failure to gastrulate by E6.0; heterozygous Ext2+/- mice develop exostoses and cartilage differentiation abnormalities independent of hedgehog signaling, demonstrating haploinsufficiency. Gene targeting (Ext2-null mice), biochemical HS assays, skeletal histology, epistasis analysis with hedgehog pathway Development (Cambridge, England) High 16236767
2007 siRNA knockdown of EXT2 in HEK293 cells produces shorter heparan sulfate chains; overexpression of EXT2 alone has no detectable effect on HS chain length, but co-overexpression of EXT1 and EXT2 together increases chain length more than EXT1 alone; a disease-associated truncation mutant EXT2-Y419X abolishes the ability of EXT2 to enhance HS chain elongation with EXT1. siRNA gene silencing, stable overexpression, HS chain-length analysis by gel filtration, truncation mutagenesis The Journal of biological chemistry High 17761672
2008 EXT2 expression level controls the amount and N-glycosylation state of NDST1 (glucosaminyl N-deacetylase/N-sulfotransferase) in cells: overexpression of EXT2 (but not EXT1) increases NDST1 protein and N-glycosylation, raises HS sulfation, and elevates NDST activity in transgenic mouse heart tissue; immunoprecipitation suggests a physical interaction between EXT2 and NDST1, supporting a GAGosome model. Overexpression in HEK293 cells, transgenic mice, NDST activity assays, immunoprecipitation, Western blotting Proceedings of the National Academy of Sciences of the United States of America Medium 18337501
2004 Zebrafish ext2 (dackel locus) is required for heparan sulfate biosynthesis in vivo; loss of ext2 causes missorting of dorsal retinal ganglion cell axons in the optic tract; genetic interaction between ext2 and extl3 double mutants phenocopies robo2 mutants, placing ext2-dependent HSPG synthesis upstream of Robo2 in axon pathfinding. Positional cloning, biochemical HS quantification, immunohistochemistry, genetic epistasis (double mutants), rescue by extl3 overexpression Neuron High 15603738
2005 Zebrafish ext2 (dackel) is required for Fgf10 signaling during pectoral fin/limb development; application of Fgf10 protein rescues target gene expression in fgf10 mutants but not in ext2 mutants; application of Fgf4 can activate target genes in ext2 mutants, revealing that ext2-dependent HSPGs selectively mediate Fgf10 but not Fgf4 signaling. Genetic epistasis, exogenous Fgf protein rescue, target gene expression (in situ hybridization), genetic interaction analysis Development (Cambridge, England) High 16221725
2011 In zebrafish ext2-null fish, chondrocytes fail to undergo terminal differentiation, pre-osteoblasts do not differentiate toward osteoblasts, and premature adipocyte differentiation occurs; runx2 expression is normal but osterix and its regulator xbp1 are impaired, placing ext2-dependent HS upstream of the osterix/xbp1 branch of osteoblast differentiation and implicating unfolded protein response in MO pathogenesis. Zebrafish ext2 null mutant analysis, molecular markers (RT-PCR, in situ hybridization), biochemical (lipid staining), morphological analysis Orphanet journal of rare diseases Medium 24628984
2011 Zebrafish ext2 mutants show reduced Fgf target gene expression and genetic interaction with Wnt11/Wnt5b morpholinos (stronger phenotype), indicating ext2-dependent HS is required for both Fgf and Wnt signaling; Hedgehog target gene expression, pathway inhibitor sensitivity, and Hh-dependent cell differentiation are unaffected in ext2 mutants, establishing pathway specificity. Zebrafish ext2 mutant analysis, pharmacological inhibition (SU5402, cyclopamine), morpholino knockdown, target gene expression by in situ hybridization BMC developmental biology Medium 21892940
2022 Cryo-EM structure of the human EXT1-EXT2 heterodimer reveals a tightly packed complex with four glycosyltransferase domains; in vitro and in cellulo mutational studies show that EXT1 can catalyze both GlcA and GlcNAc transferase reactions, while EXT2 appears to contribute predominantly N-acetylglucosamine transferase activity; heparan sulfate chain elongation is a nonprocessive process. Cryo-electron microscopy structure determination, in vitro glycosyltransferase activity assays, in cellulo mutational analysis Nature communications High 36402845
2015 Homozygous EXT2 missense mutations (p.Met87Arg and p.Arg95Cys) cause diminished EXT2 expression and reduced glycosyltransferase function in patient cells, producing a novel autosomal recessive syndrome (seizures-scoliosis-macrocephaly) without exostoses; in vitro expression of each mutant reduces EXT2 protein levels, with combined mutation having the greatest effect. Patient cell studies (Western blot, functional HS assay), in vitro expression constructs with individual and combined mutations Journal of medical genetics Medium 26246518
2016 Polyamines stimulate EXT2 translation; let-7b miRNA suppresses initiation codon recognition during EXT2 translation by binding at the N-terminal amino acid coding sequence in EXT2 mRNA, and this suppression is dependent on 5'-UTR length and is relieved by polyamines. Cell line transfection with miRNA mimics/inhibitors, reporter assays, polyamine treatment, Western blotting, ribosome profiling-type analysis Scientific reports Medium 27650265
2014 Splice mutation c.743+1G>A in EXT2 causes production of an alternative transcript with a cryptic splice site, introducing a premature stop codon; the truncated mutant mRNA undergoes nonsense-mediated decay (undetectable by western blot), resulting in haploinsufficiency of EXT2 and abnormal HS patterns in patients. Direct sequencing, mRNA analysis (RT-PCR, clone sequencing, qPCR), western blotting PloS one Medium 24728384
2011 Compound heterozygous Ext1+/-/Ext2+/- mice develop stereotypic growth plate-like exostoses along long bones (not seen in single heterozygotes), have very low heparan sulfate levels in exostoses, and fibroblasts produce shortened HS chains with reduced FGF-18 responsiveness, demonstrating that significant but not complete loss of combined Ext1/Ext2 expression drives exostosis formation. Mouse genetics (compound heterozygotes), HS immunodetection, in vitro HS chain length analysis, FGF-18 response assay Bone High 21310272
2025 EXT2 depletion in glioblastoma cells causes altered SAM/transsulfuration pathway metabolite abundance, reduced antioxidant capacity, and induction of ferroptosis (lipid peroxidation-dependent cell death); this metabolic role is distinct from its canonical heparan sulfate biosynthesis function and is linked to radiochemosensitization. RNA interference, untargeted and targeted metabolomics, lipid peroxidation assays, in vitro and in vivo tumor models, CD8+ T-cell co-culture Cell death and differentiation Medium 40234611
2002 Transgenic overexpression of EXT2 in developing mouse chondrocytes enhances heparan sulfate biosynthesis and increases trabecular bone formation; mutant EXT2 transgenic mice do not show this effect; EXT1 expression is concomitantly upregulated in both wild-type and mutant EXT2 transgenic mice, indicating interactive regulation of EXT1 and EXT2 expression. Transgenic mice (chondrocyte-specific EXT2 overexpression), histology, micro-CT, HS immunostaining, EXT1 expression analysis Biochemical and biophysical research communications Medium 11944914

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proceedings of the National Academy of Sciences of the United States of America 357 10639137
1998 The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. The Journal of biological chemistry 340 9756849
1996 The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes. Nature genetics 280 8782816
2005 Mice deficient in Ext2 lack heparan sulfate and develop exostoses. Development (Cambridge, England) 204 16236767
2007 Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation. The Journal of biological chemistry 158 17761672
1998 Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses. American journal of human genetics 156 9463333
2000 Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes. Human mutation 149 10679937
2008 Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression and heparan sulfate sulfation. Proceedings of the National Academy of Sciences of the United States of America 138 18337501
2000 The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis. EMBO reports 134 11256613
2004 Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron 131 15603738
2005 HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development (Cambridge, England) 115 16221725
2008 Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher. PLoS genetics 99 18654627
1997 Mutation screening of the EXT1 and EXT2 genes in patients with hereditary multiple exostoses. American journal of human genetics 99 9326317
2000 Comparison of fluorescent single-strand conformation polymorphism analysis and denaturing high-performance liquid chromatography for detection of EXT1 and EXT2 mutations in hereditary multiple exostoses. European journal of human genetics : EJHG 87 10713884
2003 In vitro heparan sulfate polymerization: crucial roles of core protein moieties of primer substrates in addition to the EXT1-EXT2 interaction. The Journal of biological chemistry 62 12907685
2000 Association of EXT1 and EXT2, hereditary multiple exostoses gene products, in Golgi apparatus. Biochemical and biophysical research communications 57 10679296
1996 Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2). American journal of medical genetics 55 8882796
1995 Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11. American journal of human genetics 54 7668264
2011 Compound heterozygous loss of Ext1 and Ext2 is sufficient for formation of multiple exostoses in mouse ribs and long bones. Bone 52 21310272
1998 Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas. Cancer 48 9576285
2007 Mutation screening of EXT1 and EXT2 by denaturing high-performance liquid chromatography, direct sequencing analysis, fluorescence in situ hybridization, and a new multiplex ligation-dependent probe amplification probe set in patients with multiple osteochondromas. The Journal of molecular diagnostics : JMD 47 18165274
2005 Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations. European journal of human genetics : EJHG 47 15586175
2001 Diminished levels of the putative tumor suppressor proteins EXT1 and EXT2 in exostosis chondrocytes. Cell motility and the cytoskeleton 47 11169766
2013 Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas. Scientific reports 45 23439489
2006 Determination of the mutation spectrum of the EXT1/EXT2 genes in British Caucasian patients with multiple osteochondromas, and exclusion of six candidate genes in EXT negative cases. Human mutation 43 17041877
2022 Structure of the human heparan sulfate polymerase complex EXT1-EXT2. Nature communications 32 36402845
2005 An optimized DHPLC protocol for molecular testing of the EXT1 and EXT2 genes in hereditary multiple osteochondromas. Clinical genetics 32 16283885
2016 Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas. BMC genetics 31 26961984
2005 Novel EXT1 and EXT2 mutations identified by DHPLC in Italian patients with multiple osteochondromas. Human mutation 31 16088908
2001 Mutation frequencies of EXT1 and EXT2 in 43 Japanese families with hereditary multiple exostoses. American journal of medical genetics 29 11170095
2011 Association of genetic variations in TCF7L2, SLC30A8, HHEX, LOC387761, and EXT2 with Type 2 diabetes mellitus in Tunisia. Genetic testing and molecular biomarkers 27 21510814
2015 Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme, EXT2 leads to seizure and developmental disorder, no exostoses. Journal of medical genetics 24 26246518
2009 New mutations of EXT1 and EXT2 genes in German patients with Multiple Osteochondromas. Annals of human genetics 24 19344451
2016 Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2. Scientific reports 23 27650265
1997 Isolation and characterization of the murine homolog of the human EXT2 multiple exostoses gene. Biochemical and molecular medicine 23 9232192
2018 Analysis of mutations in EXT1 and EXT2 in Brazilian patients with multiple osteochondromas. Molecular genetics & genomic medicine 22 29529714
2012 20 novel point mutations and one large deletion in EXT1 and EXT2 genes: report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis. Gene 21 23262345
2001 Familial case of Potocki-Shaffer syndrome associated with microdeletion of EXT2 and ALX4. Clinical genetics 21 11903336
2014 A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG. Scientific reports 15 25230886
2002 Transgenic expression of the EXT2 gene in developing chondrocytes enhances the synthesis of heparan sulfate and bone formation in mice. Biochemical and biophysical research communications 15 11944914
2018 A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers. Journal of veterinary internal medicine 14 29485212
1999 Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses. Journal of human genetics 14 10429361
2021 Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses. Orphanet journal of rare diseases 12 33632255
2014 A splice mutation and mRNA decay of EXT2 provoke hereditary multiple exostoses. PloS one 12 24728384
2005 Methylation status of EXT1 and EXT2 promoters and two mutations of EXT2 in chondrosarcoma. Cancer genetics and cytogenetics 12 15796962
2016 Assessing the general population frequency of rare coding variants in the EXT1 and EXT2 genes previously implicated in hereditary multiple exostoses. Bone 11 27616605
2013 Novel and recurrent mutations in the EXT1 and EXT2 genes in Chinese kindreds with multiple osteochondromas. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 11 23629877
2001 A novel deletion mutation of the EXT2 gene in a large Chinese pedigree with hereditary multiple exostosis. British journal of cancer 11 11461073
2014 Possible effects of EXT2 on mesenchymal differentiation--lessons from the zebrafish. Orphanet journal of rare diseases 10 24628984
2012 Association between variants of EXT2 and type 2 diabetes: a replication and meta-analysis. Human genetics 10 23052945
2015 Somatic loss of an EXT2 gene mutation during malignant progression in a patient with hereditary multiple osteochondromas. Cancer genetics 9 25744876
2011 EXT2-positive multiple hereditary osteochondromas with some features suggestive of metachondromatosis. Skeletal radiology 9 21892728
2011 Zebrafish Ext2 is necessary for Fgf and Wnt signaling, but not for Hh signaling. BMC developmental biology 9 21892940
2010 A splice-site mutation leads to haploinsufficiency of EXT2 mRNA for a dominant trait in a large family with multiple osteochondromas. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 9 20872591
2006 Nerve injury induces the expression of EXT2, a glycosyltransferase required for heparan sulfate synthesis. Neuroscience 9 16784821
2023 Insights into the Peritumoural Brain Zone of Glioblastoma: CDK4 and EXT2 May Be Potential Drivers of Malignancy. International journal of molecular sciences 8 36769158
2021 A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate. Genetics and molecular biology 8 34042151
2018 A novel EXT2 mutation in a consanguineous family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2). European journal of medical genetics 8 30075207
2013 Lack of replication of common EXT2 gene variants with susceptibility to type 2 diabetes in Lebanese Arabs. Diabetes & metabolism 8 23871501
2020 EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis. Frontiers in genetics 7 33414810
2016 Familial solitary chondrosarcoma resulting from germline EXT2 mutation. Genes, chromosomes & cancer 7 27636706
2013 Mutation screening for the EXT1 and EXT2 genes in Chinese patients with multiple osteochondromas. Archives of medical research 7 24120389
2011 Clinical and molecular studies of EXT1/EXT2 in Bulgaria. Journal of inherited metabolic disease 7 21499719
2009 Novel EXT1 and EXT2 mutations in hereditary multiple exostoses families of Indian origin. Genetic testing and molecular biomarkers 7 19309273
2022 Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier. Molecular genetics and genomics : MGG 6 35103870
2019 Developmental delay, coarse facial features, and epilepsy in a patient with EXT2 gene variants. Clinical case reports 6 30997052
2006 Three novel EXT1 and EXT2 gene mutations in Taiwanese patients with multiple exostoses. Journal of the Formosan Medical Association = Taiwan yi zhi 6 16638657
2014 Impact of variants of the EXT2 gene on Type 2 diabetes and its related traits in the Chinese han population. Endocrine research 5 25207843
2012 Expression of Ext1, Ext2, and heparanase genes in brain of senescence-accelerated OXYS rats in early ontogenesis and during development of neurodegenerative changes. Biochemistry. Biokhimiia 5 22339633
2009 Identification of four novel EXT1 and EXT2 mutations in five Chinese pedigrees with hereditary multiple exostoses. Genetic testing and molecular biomarkers 5 19839753
2008 Ulna/height ratio as clinical parameter separating EXT1 from EXT2 families? Genetic testing 5 18373409
2004 Hereditary multiple and isolated sporadic exostoses in the same kindred: identification of the causative gene (EXT2) and detection of a new mutation, nt112delAT, that distinguishes the two phenotypes. International journal of molecular medicine 5 14654969
2025 A novel role of exostosin glycosyltransferase 2 (EXT2) in glioblastoma cell metabolism, radiosensitivity and ferroptosis. Cell death and differentiation 4 40234611
2008 One third of Japanese patients with multiple osteochondromas may have mutations in genes other than EXT1 or EXT2. Genetic testing 4 18976157
2007 A novel mutation in the EXT2 gene identified in two unrelated Chinese families with hereditary multiple exostoses. Genetic testing 4 18294062
2022 Clinical survey of a pedigree with hereditary multiple exostoses and identification of EXT‑2 gene deletion mutation. Molecular medicine reports 3 35211766
2021 A Novel Intronic Splicing Mutation in the EXT2 Gene of a Chinese Family with Multiple Osteochondroma. Genetic testing and molecular biomarkers 3 34280007
2021 Identification of a novel EXT2 frameshift mutation in a family with hereditary multiple exostoses by whole-exome sequencing. Journal of clinical laboratory analysis 3 34403521
2020 A Novel Nonsense Mutation in the EXT2 Gene Identified in a Family with Hereditary Multiple Osteochondromas. Genetic testing and molecular biomarkers 3 32678989
2020 Hereditary multiple osteochondromas in Jordanian patients: Mutational and immunohistochemical analysis of EXT1 and EXT2 genes. Oncology letters 3 33552269
2019 Identification of a novel mutation in EXT2 in a fourth-generation Korean family with multiple osteochondromas and overview of mutation spectrum. Annals of human genetics 3 30730578
2018 A novel EXT2 frameshift mutation identified in a family with multiple osteochondromas. Oncology letters 3 30250583
2015 Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. Oncology letters 3 26870176
2009 [A new EXT2 mutation in a Chinese family with hereditary multiple exostoses]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 3 19504431
2017 Identification of mutations in EXT1 and EXT2 genes in six Chinese families with multiple osteochondromas. Molecular medicine reports 2 28849184
2016 Novel mutation of EXT2 identified in a large family with multiple osteochondromas. Molecular medicine reports 2 27748933
2008 A novel mutation in EXT2 gene in a Chinese family with hereditary multiple exostoses. Genetic testing 2 18666861
2004 [A mutation IVS2+1G>A in EXT2 gene causes hereditary multiple exostoses]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 15079787
1999 [Identification of mutations in the human EXT1 and EXT2 genes]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 10431043
2026 Multi-Omics and Single-Cell Dissection of Exostosin Glycosyltransferases (EXT1/EXT2) Reveals Divergent Oncogenic Roles and Therapeutic Vulnerabilities in Gliomas. Journal of Cancer 1 41438585
2025 Hereditary Multiple Osteochondromas and Acute Lymphoblastic Leukemia: A Possible Role for EXT1 and EXT2 in Hematopoietic Malignancies. American journal of medical genetics. Part A 1 40099867
2021 Identification of Novel Mutations in the EXT1 and EXT2 Genes of Chinese Patients with Hereditary Multiple Osteochondromas. Genetic testing and molecular biomarkers 1 33596140
2007 [EXT1 and EXT2 mutation identified by denaturing high performance liquid chromatograph in three families with hereditary multiple exostoses]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 18067075
1998 A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online. Human mutation 1 10671060
2026 EXT2 promotes sarcoma progression and immune evasion via the AKT/c-Myc/PD-L1 axis: a multi-omics and validation study. Journal of translational medicine 0 41857664
2025 EXT2 transition in adolescent membranous nephritis. Pediatric nephrology (Berlin, Germany) 0 41348129
2019 [Analysis of EXT1 and EXT2 gene mutations in two Chinese pedigrees affected with hereditary multiple exostosis]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 31030431
2014 [Mutation analysis of EXT2 gene in a family with hereditary multiple exostosis]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 25449079
2013 [Screening for EXT1 and EXT2 gene mutations in a ethnic Han Chinese family from Shanxi with hereditary multiple exostoses]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 23450490
2010 [The EXT2 gene mutation in a family with hereditary multiple exostoses]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 20140877

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