EXTL3

Chr 8AR

exostosin like glycosyltransferase 3

Also known as: BOTV, EXTL1L, EXTR1, ISDNA, REGR, RPR

NCBI Gene: 2137ENSG00000012232UniProt: O43909

This gene encodes a single-pass membrane protein which functions as a glycosyltransferase. The encoded protein catalyzes the transfer of N-acetylglucosamine to glycosaminoglycan chains. This reaction is important in heparin and heparan sulfate synthesis. Alternative splicing results in the multiple transcript variants. [provided by RefSeq, Nov 2012]

Primary Disease Associations & Inheritance

Immunoskeletal dysplasia with neurodevelopmental abnormalitiesMIM #617425
AR
0
Active trials
16
Pathogenic / LP
389
ClinVar variants
2
Pubs (1 yr)
1.5
Missense Z
0.68
LOEUF
Clinical Summary— EXTL3
🧬
Gene-Disease Validity (ClinGen)
immunoskeletal dysplasia with neurodevelopmental abnormalities · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 165 VUS of 389 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 2.94
OE 0.43 (0.28–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.48Z-score
OE missense 0.82 (0.76–0.89)
458 obs / 556.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.28–0.68)
0≤0.351.4
Missense OE0.82 (0.76–0.89)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 13 / 30.5Missense obs/exp: 458 / 556.0Syn Z: -1.29

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS165
Likely Benign203
Benign4
Conflicting1
16
Pathogenic
165
VUS
203
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
2
155
8
0
165
Likely Benign
0
1
33
169
203
Benign
0
0
2
2
4
Conflicting
—1
Total215659171389

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

View in ClinVar →

EXTL3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EXTL3-related neuro immuno skeletal dysplasia syndrome

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients