EXT1 Gene: Exostosin Glycosyltransferase 1
EXT1 encodes a glycosyltransferase essential for heparan sulfate synthesis; mutations cause hereditary multiple exostoses and contribute to cancer.
Gene Information Card
| Symbol | EXT1 |
|---|---|
| Full Name | Exostosin Glycosyltransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.11 |
| NCBI Gene ID | 2131 ncbi.nlm.nih.gov/gene/2131 |
| Ensembl ID | ENSG00000182197 |
| UniProt ID | Q16394 |
| OMIM ID | 608177 |
| HGNC ID | 3512 |
| Aliases | EXT, LGCR, TRPS2, hereditary multiple exostoses type 1 |
Description
The EXT1 gene encodes exostosin glycosyltransferase 1, a type II transmembrane glycoprotein localized to the endoplasmic reticulum and Golgi apparatus. It functions as a glycosyltransferase involved in the biosynthesis of heparan sulfate, a key component of the extracellular matrix and cell surface proteoglycans. EXT1 forms a hetero-oligomeric complex with EXT2 to catalyze the polymerization of heparan sulfate chains. Mutations in EXT1 lead to hereditary multiple exostoses (HME), an autosomal dominant disorder characterized by multiple benign bone tumors (osteochondromas). Loss of EXT1 function also contributes to malignant transformation, particularly in chondrosarcoma and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary multiple exostoses (HME) | Loss-of-function mutations in EXT1 impair heparan sulfate synthesis, leading to abnormal bone growth and osteochondroma formation. | OMIM: 133700; ClinVar: pathogenic variants |
| Chondrosarcoma | Somatic mutations or loss of heterozygosity at EXT1 locus in osteochondromas can lead to malignant progression. | COSMIC: mutations in cancer samples; studies show EXT1 loss in chondrosarcoma |
| Osteochondroma (sporadic) | Somatic EXT1 mutations or deletions in cartilage cap cells cause benign tumor formation. | ClinVar: somatic variants; literature evidence |
| Multiple osteochondromas (MO) | Same as HME; EXT1 mutations account for ~70% of cases. | OMIM: 133700; HGNC: 3512 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Brain | 8.4 | Low |
| Lung | 7.1 | Low |
| Heart | 6.3 | Low |
| Skeletal muscle | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line; high expression |
| A549 | 9.8 | Lung carcinoma; moderate expression |
| MCF7 | 7.2 | Breast adenocarcinoma; low expression |
| K562 | 6.5 | Chronic myeloid leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1465delT (p.Ser489Profs*23) | Frameshift | Rare (found in HME families) | Loss of function; truncated protein |
| c.1030C>T (p.Arg344*) | Nonsense | Rare | Premature stop; loss of function |
| c.1171G>A (p.Gly391Arg) | Missense | Rare | Impaired glycosyltransferase activity |
| c.1550T>C (p.Leu517Pro) | Missense | Rare | Altered protein folding; loss of function |
| Whole gene deletion | Copy number loss | Rare | Loss of heterozygosity; tumor suppressor inactivation |
Mutation functional classification
Loss of Function (LOF)
Most EXT1 mutations are loss-of-function, leading to haploinsufficiency or complete loss of glycosyltransferase activity, resulting in reduced heparan sulfate synthesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for EXT1; all pathogenic variants are loss-of-function.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by disrupting the EXT1-EXT2 complex, but evidence is limited; most cases are due to haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Heparan sulfate biosynthesis (Reactome: R-HSA-2024096)
• Glycosaminoglycan metabolism (KEGG: hsa00532)
• Proteoglycans in cancer (KEGG: hsa05205)
Protein Summary
Exostosin glycosyltransferase 1 (EXT1) is a 746-amino acid type II transmembrane protein with a molecular weight of ~85 kDa. It localizes to the endoplasmic reticulum and Golgi apparatus, where it forms a heterodimeric complex with EXT2 to catalyze the alternating addition of glucuronic acid and N-acetylglucosamine residues to growing heparan sulfate chains. EXT1 is essential for normal skeletal development and acts as a tumor suppressor in bone and cartilage. Its structure includes a cytoplasmic N-terminus, a transmembrane domain, and a large luminal catalytic domain. Mutations that disrupt its enzymatic activity lead to hereditary multiple exostoses and increase cancer risk.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EXT1 Knockout HEK293 Cell Line | EDJ-KQ3290 | Human | 2131 | Details Get a Quote |
| EXT1 Knockout A-549 Cell Line | EDJ-KQ24865 | Human | 2131 | Details Get a Quote |
| EXT1 Knockout HCT 116 Cell Line | EDJ-KQ24866 | Human | 2131 | Details Get a Quote |
| EXT1 Knockout HeLa Cell Line | EDJ-KQ24867 | Human | 2131 | Details Get a Quote |
| EXT1 (p.E587=) Point Mutation in HAP1 Cell Line | EDC03475 | Human | 2131 | Details Get a Quote |
