EXTL1

Chr 1

exostosin like glycosyltransferase 1

Also known as: EXTL

EXTL1 encodes a glycosyltransferase that transfers N-acetylglucosamine during heparan sulfate biosynthesis, which is essential for proper cell signaling and development. Mutations cause skeletal dysplasia with multiple osteochondromas, developmental delay, and intellectual disability through autosomal recessive inheritance. The gene shows extremely high constraint against loss-of-function variants, indicating its critical importance for normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.08
Clinical SummaryEXTL1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 107 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.22
OE 0.75 (0.531.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.90Z-score
OE missense 0.87 (0.800.95)
336 obs / 386.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.75 (0.531.08)
00.351.4
Missense OE0.87 (0.800.95)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 21 / 27.9Missense obs/exp: 336 / 386.0Syn Z: 0.17

ClinVar Variant Classifications

133 submitted variants in ClinVar

Classification Summary

Pathogenic5
VUS107
Likely Benign12
5
Pathogenic
107
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
103
4
0
107
Likely Benign
0
12
0
0
12
Benign
0
0
0
0
0
Total011590124

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EXTL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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