EXT2

Chr 11ADAR

exostosin glycosyltransferase 2

Also known as: SOTV, SSMS

NCBI Gene: 2132ENSG00000151348UniProt: Q93063

This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Exostoses, multiple, type 2MIM #133701
AD
Exostoses, multiple, type 2MIM #133701
AD
Seizures, scoliosis, and macrocephaly syndromeMIM #616682
AR
UniProtHereditary multiple exostoses 2
482
ClinVar variants
96
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EXT2
🧬
Gene-Disease Validity (ClinGen)
exostoses, multiple, type 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
96 Pathogenic / Likely Pathogenic· 248 VUS of 482 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.77LOEUF
pLI 0.000
Z-score 2.73
OE 0.53 (0.38–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.64Z-score
OE missense 0.91 (0.84–0.99)
394 obs / 431.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.38–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.84–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 21 / 39.5Missense obs/exp: 394 / 431.4Syn Z: -0.24

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic28
VUS248
Likely Benign131
Benign2
Conflicting5
68
Pathogenic
28
Likely Pathogenic
248
VUS
131
Likely Benign
2
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
47
0
21
0
68
Likely Pathogenic
14
5
9
0
28
VUS
4
228
13
3
248
Likely Benign
0
1
49
81
131
Benign
0
1
1
0
2
Conflicting
—5
Total652359384482

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

View in ClinVar →

Protein Context — Lollipop Plot

EXT2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EXT2-related multiple exostoses

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersCancerSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Exostoses, multiple, type 2

MIM #133701

Molecular basis of disorder known

Autosomal dominant

Exostoses, multiple, type 2

MIM #133701

Molecular basis of disorder known

Autosomal dominant

Seizures, scoliosis, and macrocephaly syndrome

MIM #616682

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EXT2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
New 'Antigens' in Membranous Nephropathy.
Sethi S·J Am Soc Nephrol
2021Review
Mechanisms of Primary Membranous Nephropathy.
Gu Y et al.·Biomolecules
2021Review
Exostosin 1/Exostosin 2-Associated Membranous Nephropathy.
Sethi S et al.·J Am Soc Nephrol
2019
Genetics of short stature.
Nicolae R et al.·Curr Opin Pediatr
2025Review
Antigens in membranous nephropathy: discovery and clinical implications.
Sethi S et al.·Nat Rev Nephrol
2025Review
Membranous nephropathy-diagnosis and identification of target antigens.
Sethi S et al.·Nephrol Dial Transplant
2024Review
Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer.
Lee NY et al.·Hum Genomics
2023Cohort
Multiple osteochondromas.
Bovée JV·Orphanet J Rare Dis
2008Review
Dual-antigen membranous nephropathy.
Nasr SH et al.·Kidney Int
2026
Pediatric membranous nephropathy: In the novel antigens era.
Huang G et al.·Front Immunol
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools