DSE

Chr 6AR

dermatan sulfate epimerase

NCBI Gene: 29940ENSG00000111817UniProt: Q9UL01

Converts D-glucuronic acid to L-iduronic acid (IdoUA) residues. Plays an important role in the biosynthesis of the glycosaminoglycan/mucopolysaccharide dermatan sulfate

Primary Disease Associations & Inheritance

Ehlers-Danlos syndrome, musculocontractural type 2MIM #615539
AR
591
ClinVar variants
36
Pathogenic / LP
0.63
pLI score
0
Active trials
Clinical Summary— DSE
🧬
Gene-Disease Validity (ClinGen)
Ehlers-Danlos syndrome, musculocontractural type 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 312 VUS of 591 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.38LOEUF
pLI 0.633
Z-score 4.54
OE 0.21 (0.12–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.03Z-score
OE missense 0.75 (0.69–0.82)
393 obs / 523.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.21 (0.12–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.82)
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.0.90
0≤1.21.6
LoF obs/exp: 8 / 38.3Missense obs/exp: 393 / 523.4Syn Z: 1.08

ClinVar Variant Classifications

591 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic10
VUS312
Likely Benign202
Benign26
Conflicting15
26
Pathogenic
10
Likely Pathogenic
312
VUS
202
Likely Benign
26
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
23
0
26
Likely Pathogenic
4
0
6
0
10
VUS
6
289
15
2
312
Likely Benign
0
19
25
158
202
Benign
0
6
16
4
26
Conflicting
—15
Total1231585164591

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

View in ClinVar →

Protein Context — Lollipop Plot

DSE · protein map & ClinVar variants

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

Gene2Phenotype Curations

DSE-related Ehlers-Danlos syndrome, musculocontractural

limited
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ehlers-Danlos syndrome, musculocontractural type 2

MIM #615539

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DSE
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY.
Garvey WT et al.·Endocr Pract
2016Guideline
Airway Ultrasound as Predictor of Difficult Direct Laryngoscopy: A Systematic Review and Meta-analysis.
Carsetti A et al.·Anesth Analg
2022Meta-analysis
DSE associated musculocontractural EDS, a milder phenotype or phenotypic variability.
Schirwani S et al.·Eur J Med Genet
2020Review
Vascular aspects of the Ehlers-Danlos Syndromes.
Malfait F·Matrix Biol
2018Review
Recent Advances in the Pathophysiology of Musculocontractural Ehlers-Danlos Syndrome.
Kosho T et al.·Genes (Basel)
2019Review
Two-dimensional ECG-based cardiac arrhythmia classification using DSE-ResNet.
Li J et al.·Sci Rep
2022
Ehlers Danlos Syndrome with Glycosaminoglycan Abnormalities.
Miyake N et al.·Adv Exp Med Biol
2021
Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting.
Arjomandi Rad A et al.·Clin Cardiol
2024Meta-analysis
Stress echocardiography in patients with native valvular heart disease.
Lancellotti P et al.·Heart
2018Review
Clinical and molecular features of 66 patients with musculocontractural Ehlers-Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14).
Minatogawa M et al.·J Med Genet
2022Cohort
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