GLB1

Chr 3AR

galactosidase beta 1

Also known as: EBP, ELNR1, MPS4B

NCBI Gene: 2720 ENSG00000170266 UniProt: P16278 OMIM: 611458

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the glycosyl hydrolase 35 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature lysosomal enzyme. This enzyme catalyzes the hydrolysis of a terminal beta-linked galactose residue from ganglioside substrates and other glycoconjugates. Mutations in this gene may result in GM1-gangliosidosis and Morquio B syndrome. [provided by RefSeq, Nov 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.864 OMIM phenotypes

Clinical Summary— GLB1

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Gene-Disease Validity (ClinGen)

GM1 gangliosidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

335 unique Pathogenic / Likely Pathogenic· 327 VUS of 1336 total submissions

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Clinical Trials

6 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GLB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.20

OE 0.59 (0.42–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.79Z-score

OE missense 0.88 (0.81–0.97)

333 obs / 376.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.42–0.86)

0≤0.351.4

Missense OE?0.88 (0.81–0.97)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

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

This gene — mechanism propensity

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

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

1336 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic128

Likely Pathogenic207

VUS327

Likely Benign529

Benign65

Conflicting55

128

Pathogenic

207

Likely Pathogenic

327

VUS

529

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	82	33	13	0	128
Likely Pathogenic	86	118	3	0	207
VUS	10	292	24	1	327
Likely Benign	0	26	213	290	529
Benign	0	3	57	5	65
Conflicting	—				55
Total	178	472	310	296	1,311

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap GLB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →