EXT1
Chr 8ADSomaticexostosin glycosyltransferase 1
Also known as: EXT, LGCR, LGS, TRPS2, TTV
This gene encodes an endoplasmic reticulum glycosyltransferase that catalyzes heparan sulfate chain elongation during biosynthesis. Loss-of-function mutations cause multiple exostoses type 1, an autosomal dominant disorder characterized by benign bone tumors that can undergo malignant transformation to chondrosarcoma. The pathogenic mechanism involves haploinsufficiency leading to disrupted heparan sulfate production and abnormal bone growth regulation.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 25 | 4 | 12 | 0 | 41 |
Likely Pathogenic | 3 | 0 | 0 | 0 | 3 |
VUS | 1 | 25 | 3 | 1 | 30 |
Likely Benign | 0 | 0 | 5 | 11 | 16 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 29 | 29 | 20 | 12 | 90 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EXT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools