GLB1

Chr 3AR

galactosidase beta 1

NCBI Gene: 2720ENSG00000170266UniProt: P16278

Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans

Primary Disease Associations & Inheritance

GM1-gangliosidosis, type IMIM #230500
AR
GM1-gangliosidosis, type IIMIM #230600
AR
GM1-gangliosidosis, type IIIMIM #230650
AR
Mucopolysaccharidosis type IVB (Morquio)MIM #253010
AR
1338
ClinVar variants
94
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— GLB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
94 Pathogenic / Likely Pathogenic· 144 VUS of 1338 total submissions
💊
Clinical Trials
4 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.
0.86LOEUF
pLI 0.000
Z-score 2.20
OE 0.59 (0.42–0.86)
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.
0.79Z-score
OE missense 0.88 (0.81–0.97)
333 obs / 376.4 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.0.59 (0.42–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.81–0.97)
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.0.95
0≤1.21.6
LoF obs/exp: 20 / 33.8Missense obs/exp: 333 / 376.4Syn Z: 0.43

ClinVar Variant Classifications

1338 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic48
VUS144
Likely Benign235
Benign4
Conflicting2
46
Pathogenic
48
Likely Pathogenic
144
VUS
235
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
6
17
0
46
Likely Pathogenic
13
30
5
0
48
VUS
1
133
10
0
144
Likely Benign
0
9
115
111
235
Benign
0
1
3
0
4
Conflicting
—2
Total37179150111479

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

View in ClinVar →

Protein Context — Lollipop Plot

GLB1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GLB1-related GM1-gangliosidosis, type 3

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

GM1-gangliosidosis, type I

MIM #230500

Molecular basis of disorder known

Autosomal recessive

GM1-gangliosidosis, type II

MIM #230600

Molecular basis of disorder known

Autosomal recessive

GM1-gangliosidosis, type III

MIM #230650

Molecular basis of disorder known

Autosomal recessive

Mucopolysaccharidosis type IVB (Morquio)

MIM #253010

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence.
Qi Z et al.·Autophagy
2024
Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.
Livingston MJ et al.·Autophagy
2023
PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.
Araya J et al.·Autophagy
2019
Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.
Cheng Z et al.·Autophagy
2025
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking.
Song Y et al.·Autophagy
2024
Autophagy regulates cellular senescence by mediating the degradation of CDKN1A/p21 and CDKN2A/p16 through SQSTM1/p62-mediated selective autophagy in myxomatous mitral valve degeneration.
Tang Q et al.·Autophagy
2025
Genotype-Phenotype Relations for the Dystonia-Parkinsonism Genes GLB1, SLC6A3, SLC30A10, SLC39A14, and PLA2G6: MDSGene Systematic Review.
Rodriguez-Antiguedad J et al.·Int J Mol Sci
2025Review
KDM4A-induced tumor senescence enhances the efficacy of immunotherapy by inhibiting AGT-PHB1 axis-mediated mitophagy in colorectal cancer.
Cai T et al.·Autophagy
2025
Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex.
Yuskiv N et al.·Int J Mol Sci
2020Review
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
Lysosomal DiseasesGangliosidosisGM1

A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis

RECRUITING
NCT03952637Phase PHASE1, PHASE2National Human Genome Research Institute (NHGRI)Started 2019-08-19
AAV9-GLB1Abdominal ultrasoundRituximab
GM1 GangliosidosisGM1 Gangliosidosis, Type IGM1 Gangliosidosis, Type 2

Study of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Participants With GM1 Gangliosidosis

ACTIVE NOT RECRUITING
NCT04713475Phase PHASE1, PHASE2Gemma BiotherapeuticsStarted 2021-03-17
PBGM01
Obesity & Overweight

Supplementation With Sirtuin Activators in Women With Increased Body Weight

RECRUITING
NCT07245979Phase NAPoznan University of Life SciencesStarted 2025-10-08
Sirtuin activatorsPlacebo
Lactose IntoleranceLactose IntolerantLactase Persistence

Milk for Diabetes Prevention

NOT YET RECRUITING
NCT06513026Phase NAAlbert Einstein College of MedicineStarted 2026-02
Lactose-Containing MilkLactose-Free Milk

External Resources

Links to major genomics databases and tools