GLB1

Chr 3AR

galactosidase beta 1

The protein is a lysosomal enzyme that catalyzes the hydrolysis of terminal beta-linked galactose residues from ganglioside substrates and other glycoconjugates. Mutations cause autosomal recessive GM1-gangliosidosis (types I, II, and III) and Morquio B syndrome (mucopolysaccharidosis type IVB) through loss of function. The predicted mechanism of pathogenicity is dominant negative.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.864 OMIM phenotypes
Clinical SummaryGLB1
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Gene-Disease Validity (ClinGen)
GM1 gangliosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.20
OE 0.59 (0.420.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.79Z-score
OE missense 0.88 (0.810.97)
333 obs / 376.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.420.86)
00.351.4
Missense OE0.88 (0.810.97)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 20 / 33.8Missense obs/exp: 333 / 376.4Syn Z: 0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGLB1-related GM1-gangliosidosis, type 3LOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.6053th %ile
LOF
0.2287th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

GM1 GangliosidosesGM1 Gangliosidosis, Type IGM1 Gangliosidosis, Type 2

Prenatal Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis Clinical Trial

NOT YET RECRUITING
NCT07479953Phase PHASE1Tippi MackenzieStarted 2026-06-01
Gene Transfer with an AAV9 Vector Expressing Human ß-galactosidase
HIV InfectionsAlcohol DrinkingAging

Precision Microbiota Interventions for Senoreduction Trial

NOT YET RECRUITING
NCT07462767Phase PHASE1, PHASE2Louisiana State University Health Sciences Center in New OrleansStarted 2026-04-01
Limosilactobacillus reuteriBlueberry extract
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
Lactose IntoleranceLactose IntolerantLactase Persistence

Milk for Diabetes Prevention

RECRUITING
NCT06513026Phase NAAlbert Einstein College of MedicineStarted 2026-04
Lactose-Containing MilkLactose-Free Milk
Obesity & Overweight

Supplementation With Sirtuin Activators in Women With Increased Body Weight

RECRUITING
NCT07245979Phase NAPoznan University of Life SciencesStarted 2025-10-08
Sirtuin activatorsPlacebo
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
Clinical Literature
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