SGSH

Chr 17AR

N-sulfoglucosamine sulfohydrolase

NCBI Gene: 6448ENSG00000181523UniProt: P51688

Catalyzes a step in lysosomal heparan sulfate degradation

Primary Disease Associations & Inheritance

Mucopolysaccharidosis type IIIA (Sanfilippo A)MIM #252900
AR
1718
ClinVar variants
80
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— SGSH
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
80 Pathogenic / Likely Pathogenic· 178 VUS of 1718 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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.
0.80LOEUF
pLI 0.000
Z-score 2.24
OE 0.47 (0.29–0.80)
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.
-0.05Z-score
OE missense 1.01 (0.92–1.10)
336 obs / 333.2 exp
Tolerant

Tolerant to missense variation

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.0.47 (0.29–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.10)
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.1.09
0≤1.21.6
LoF obs/exp: 10 / 21.1Missense obs/exp: 336 / 333.2Syn Z: -0.91

ClinVar Variant Classifications

1718 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic51
VUS178
Likely Benign211
Conflicting6
29
Pathogenic
51
Likely Pathogenic
178
VUS
211
Likely Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
2
15
0
29
Likely Pathogenic
24
15
12
0
51
VUS
11
146
14
7
178
Likely Benign
0
2
84
125
211
Benign
0
0
0
0
0
Conflicting
—6
Total47165125132475

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

View in ClinVar →

Protein Context — Lollipop Plot

SGSH · protein map & ClinVar variants

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

Gene2Phenotype Curations

SGSH-related mucopolysaccharidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mucopolysaccharidosis type IIIA (Sanfilippo A)

MIM #252900

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
A novel mutation of SGSH and clinical features analysis of mucopolysaccharidosis type IIIA.
Li X et al.·Medicine (Baltimore)
2018Case report
Sanfilippo syndrome: Overall review.
Andrade F et al.·Pediatr Int
2015Review
How close are we to therapies for Sanfilippo disease?
Gaffke L et al.·Metab Brain Dis
2018Review
Glycosaminoglycans and mucopolysaccharidosis type III.
Jakobkiewicz-Banecka J et al.·Front Biosci (Landmark Ed)
2016Review
Oncological Aspects of Lysosomal Storage Diseases.
Ługowska A·Cells
2024Review
Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications.
Yogalingam G et al.·Hum Mutat
2001Review
An immune deficient mouse model for mucopolysaccharidosis IIIA (Sanfilippo syndrome).
Pollock K et al.·Sci Rep
2023Functional
Overcoming Limitations Inherent in Sulfamidase to Improve Mucopolysaccharidosis IIIA Gene Therapy.
Chen Y et al.·Mol Ther
2018
The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome).
Meyer A et al.·Hum Mutat
2008
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
MPS IIIASanfilippo SyndromeSanfilippo A

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH

RECRUITING
NCT02716246Phase PHASE2, PHASE3Ultragenyx Pharmaceutical IncStarted 2016-04-25
UX111Prophylactic Immunomodulatory (IM) TherapyOptimized Prophylactic IM Therapy
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History
Mucopolysaccharidosis Type IIIA

Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type IIIA

ACTIVE NOT RECRUITING
NCT04201405Phase PHASE1, PHASE2University of ManchesterStarted 2020-01-07
Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene

External Resources

Links to major genomics databases and tools