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…

Primary Disease Associations & Inheritance

GM1-gangliosidosis, type IMIM #230500

GM1-gangliosidosis, type IIMIM #230600

GM1-gangliosidosis, type IIIMIM #230650

Mucopolysaccharidosis type IVB (Morquio)MIM #253010

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in GLB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

908 rare PASS variants

Rare truncating (LoF)

1 in 1,200

138 rare PASS variants

Rare synonymous (reference)

1 in 120

356 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GLB1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,500
South Asian	~43k	1 in 55	1 in 490
Remaining (unassigned)	~30k	1 in 61	1 in 510
European (Finnish)	~27k	1 in 160	≈ 1 in 27,000
Admixed American	~22k	1 in 51	1 in 1,500
African / African American	~21k	1 in 61	1 in 720
East Asian	~20k	1 in 65	1 in 740
Ashkenazi Jewish	~13k	1 in 260	none seen
Middle Eastern	~2,884	1 in 50	≈ 1 in 880

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓