GUSB

Chr 7AR

glucuronidase beta

Also known as: BG, MPS7

NCBI Gene: 2990ENSG00000169919UniProt: P08236

This gene encodes a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. Mutations in this gene result in mucopolysaccharidosis type VII. Alternative splicing results in multiple transcript variants. There are many pseudogenes of this locus in the human genome.[provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Mucopolysaccharidosis VIIMIM #253220
AR
689
ClinVar variants
92
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GUSB
🧬
Gene-Disease Validity (ClinGen)
mucopolysaccharidosis type 7 · ARDefinitive

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
92 Pathogenic / Likely Pathogenic· 207 VUS of 689 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.
0.75LOEUF
pLI 0.000
Z-score 2.71
OE 0.51 (0.35–0.75)
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.
1.10Z-score
OE missense 0.84 (0.77–0.92)
315 obs / 374.9 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.0.51 (0.35–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.77–0.92)
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.1.08
0≤1.21.6
LoF obs/exp: 18 / 35.4Missense obs/exp: 315 / 374.9Syn Z: -0.80

ClinVar Variant Classifications

689 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic46
VUS207
Likely Benign368
Benign9
Conflicting13
46
Pathogenic
46
Likely Pathogenic
207
VUS
368
Likely Benign
9
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
1
22
0
46
Likely Pathogenic
19
18
9
0
46
VUS
4
174
27
2
207
Likely Benign
1
10
136
221
368
Benign
0
0
8
1
9
Conflicting
—13
Total47203202224689

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

View in ClinVar →

Protein Context — Lollipop Plot

GUSB · protein map & ClinVar variants

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

Gene2Phenotype Curations

GUSB-related mucopolysaccharidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
BETA-GLUCURONIDASE; GUSB
MIM #611499 · *

Mucopolysaccharidosis VII

MIM #253220

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GUSB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gut dysbiosis-derived β-glucuronidase promotes the development of endometriosis.
Wei Y et al.·Fertil Steril
2023
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.
Pierre L et al.·Autophagy
2025
Anti-psoriasis effect of 18β-glycyrrhetinic acid by breaking CCL20/CCR6 axis through its vital active group targeting GUSB/ATF2 signaling.
Wei J et al.·Phytomedicine
2024
Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome).
Tomatsu S et al.·Hum Mutat
2009Review
Bioinformatics prediction and experimental verification identify B4GALT1 as a diagnostic biomarker of glioblastoma.
Lu X et al.·Int J Biol Macromol
2025
Over-Expression of GUSB Leads to Primary Resistance of Anti-PD1 Therapy in Hepatocellular Carcinoma.
Kong X et al.·Front Immunol
2022
High Prevalence of GALC Gene Variants in Adults With Neurodegenerative Conditions.
Feo F et al.·Eur J Neurol
2025
Mucopolysaccharidosis type VII (Sly syndrome) - What do we know?
Grant CL et al.·Mol Genet Metab
2024Review
Mucopolysaccharidosis VII in Brazil: natural history and clinical findings.
Giugliani R et al.·Orphanet J Rare Dis
2021Review
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