EXT1

Chr 8ADSomatic

exostosin 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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/SomaticLOEUF 0.263 OMIM phenotypes
Clinical SummaryEXT1
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Gene-Disease Validity (ClinGen)
exostoses, multiple, type 1 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.997
Z-score 4.86
OE 0.11 (0.060.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.67Z-score
OE missense 0.77 (0.700.84)
317 obs / 412.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.060.26)
00.351.4
Missense OE0.77 (0.700.84)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 4 / 35.0Missense obs/exp: 317 / 412.2Syn Z: -0.73
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEXT1-related multiple exostosesLOFAD
definitiveEXT1-related trichorhinopharangeal syndrome (Langer-Giedon)LOFAD
DN
0.3793th %ile
GOF
0.3292th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.26

Literature Evidence

LOFLanger-Giedion's syndrome (LGS) or trichorhinophalangeal syndrome type II (TRPS II; MIM:150230) is a contiguous gene deletion syndrome caused by the haploinsufficiency of the TRPS1 and EXT1 genes.PMID:31976145

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

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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