mucopolysaccharidosis type 4B

Summary

mucopolysaccharidosis type 4B (MONDO:0009660) is a disease caused by GLB1 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (United States) [Orphanet-validated]
• Causal gene: GLB1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 1,022

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.001	United States	Validated
Prevalence at birth	<1 / 1 000 000	0.004	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	mucopolysaccharidosis type 4B
Mondo ID	MONDO:0009660
OMIM	253010
Orphanet	309310
DOID	DOID:0111392
ICD-10-CM	E76.211
ICD-11	1479415032
NCIT	C84902
SNOMED CT	238044004
UMLS	C0086652
MedGen	43376
GARD	0003786
Is cancer (heuristic)	no

Also known as: Beta-D-galactosidase deficiency · Morquio disease type B · Morquio syndrome B · MPS 4B · MPS IV B · MPS IVB · MPS4B · MPSIVB · mucopolysaccharidosis type IVB

Data availability: 1,022 ClinVar variants · 4 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › mucopolysaccharidosis type 4 › mucopolysaccharidosis type 4B

Related subtypes (2): Morquio syndrome C, mucopolysaccharidosis type 4A

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

337 likely benign, 131 uncertain significance, 50 pathogenic, 26 pathogenic/likely pathogenic, 21 likely pathogenic, 19 conflicting classifications of pathogenicity, 11 benign, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1057305	NM_000404.4(GLB1):c.1388T>C (p.Leu463Pro)	GLB1	Pathogenic	criteria provided, single submitter
1063917	NM_000404.4(GLB1):c.107A>G (p.Tyr36Cys)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066585	NM_000404.4(GLB1):c.557A>C (p.Glu186Ala)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067823	NM_000404.4(GLB1):c.2006dup (p.Asn669fs)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069437	NM_000404.4(GLB1):c.473del (p.Val158fs)	GLB1	Pathogenic	criteria provided, single submitter
1069817	NM_000404.4(GLB1):c.1324C>T (p.Arg442Ter)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070505	NM_000404.4(GLB1):c.1258A>C (p.Thr420Pro)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071414	NM_000404.4(GLB1):c.994G>A (p.Asp332Asn)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075170	NM_000404.4(GLB1):c.964_965del (p.Ser322fs)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075413	NM_000404.4(GLB1):c.1699C>T (p.Gln567Ter)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076248	NM_000404.4(GLB1):c.1580G>A (p.Trp527Ter)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1077168	NM_000404.4(GLB1):c.75+2T>G	GLB1	Pathogenic	no assertion criteria provided
1251981	NM_000404.4(GLB1):c.1010T>C (p.Leu337Pro)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1301844	NM_000404.4(GLB1):c.998A>G (p.Tyr333Cys)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332777	NM_000404.4(GLB1):c.425_428del (p.Lys142fs)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1353182	NM_000404.4(GLB1):c.569G>A (p.Gly190Asp)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1355177	NM_000404.4(GLB1):c.257G>A (p.Trp86Ter)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1364568	NM_000404.4(GLB1):c.1479+1G>C	GLB1	Pathogenic	criteria provided, single submitter
1372550	NM_000404.4(GLB1):c.1276T>G (p.Cys426Gly)	GLB1	Pathogenic	criteria provided, single submitter
1378674	NM_000404.4(GLB1):c.1576_1583dup (p.His529fs)	GLB1	Pathogenic	criteria provided, single submitter
1382131	NM_000404.4(GLB1):c.1616G>A (p.Trp539Ter)	GLB1	Pathogenic	criteria provided, single submitter
1395005	NM_000404.4(GLB1):c.424A>T (p.Lys142Ter)	GLB1	Pathogenic	criteria provided, single submitter
1405477	NM_000404.4(GLB1):c.1336dup (p.Ala446fs)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1419594	NM_000404.4(GLB1):c.246-2A>G	GLB1	Pathogenic	criteria provided, single submitter
1434135	NM_000404.4(GLB1):c.1574_1583del (p.Gly525fs)	GLB1	Pathogenic	criteria provided, single submitter
1449094	NM_000404.4(GLB1):c.591dup (p.Asp198Ter)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1452262	NM_000404.4(GLB1):c.397G>T (p.Gly133Ter)	GLB1	Pathogenic	criteria provided, single submitter
1454377	NM_000404.4(GLB1):c.1142del (p.Lys381fs)	GLB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457406	NM_000404.4(GLB1):c.1587_1590dup (p.Asp531delinsProTer)	GLB1	Pathogenic	criteria provided, single submitter
1457739	NM_000404.4(GLB1):c.1310del (p.Asn437fs)	GLB1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 23 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GLB1	Strong	Autosomal recessive	mucopolysaccharidosis type 4B	23

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GLB1	Orphanet:309310	Mucopolysaccharidosis type 4B
GLB1	Orphanet:79255	GM1 gangliosidosis type 1
GLB1	Orphanet:79256	GM1 gangliosidosis type 2
GLB1	Orphanet:79257	GM1 gangliosidosis type 3

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	gencc,clinvar
TMPPE	HGNC:33865	ENSG00000188167	Q6ZT21	Transmembrane protein with metallophosphoesterase domain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf
TMPPE	Other/Unknown	no		Calcineurin-like_PHP, Metallo-depent_PP-like, Metallophosphoesterase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
mononuclear cell	1
stromal cell of endometrium	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLB1	258	ubiquitous	marker	monocyte, mononuclear cell, stromal cell of endometrium
TMPPE	132	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLB1	1,578
TMPPE	674

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GLB1	P16278	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMPPE	Q6ZT21	91.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IV - Morquio syndrome B (Keratin metabolism)	1	5710.0×	0.003	GLB1
MPS IV - Morquio syndrome B (CS/DS degradation)	1	5710.0×	0.003	GLB1
Defective NEU1 causes sialidosis	1	2855.0×	0.004	GLB1
Mucopolysaccharidoses	1	1903.3×	0.004	GLB1
Diseases of carbohydrate metabolism	1	815.7×	0.005	GLB1
Keratan sulfate degradation	1	713.8×	0.005	GLB1
Diseases associated with N-glycosylation of proteins	1	634.4×	0.005	GLB1
Heparan sulfate/heparin (HS-GAG) metabolism	1	543.8×	0.005	GLB1
CS/DS degradation	1	543.8×	0.005	GLB1
Keratan sulfate/keratin metabolism	1	496.5×	0.005	GLB1
HS-GAG degradation	1	496.5×	0.005	GLB1
Sialic acid metabolism	1	326.3×	0.007	GLB1
Glycosphingolipid metabolism	1	300.5×	0.007	GLB1
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.007	GLB1
Glycosphingolipid catabolism	1	292.8×	0.007	GLB1
Glycosaminoglycan metabolism	1	219.6×	0.008	GLB1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.008	GLB1
Sphingolipid metabolism	1	167.9×	0.010	GLB1
Diseases of glycosylation	1	131.3×	0.012	GLB1
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.012	GLB1
Diseases of metabolism	1	80.4×	0.018	GLB1
Asparagine N-linked glycosylation	1	60.1×	0.023	GLB1
Metabolism of lipids	1	31.6×	0.041	GLB1
Innate Immune System	1	25.5×	0.049	GLB1
Neutrophil degranulation	1	23.1×	0.052	GLB1
Post-translational protein modification	1	19.2×	0.060	GLB1
Disease	1	13.1×	0.083	GLB1
Immune System	1	13.0×	0.083	GLB1
Metabolism of proteins	1	12.4×	0.084	GLB1
Metabolism	1	11.6×	0.086	GLB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to cortisone	1	8426.0×	4e-04	GLB1
keratan sulfate proteoglycan catabolic process	1	5617.3×	4e-04	GLB1
response to Thyroglobulin triiodothyronine	1	5617.3×	4e-04	GLB1
galactose catabolic process	1	2808.7×	6e-04	GLB1
ganglioside catabolic process	1	1872.4×	7e-04	GLB1
glycoprotein catabolic process	1	1053.2×	0.001	GLB1
carbohydrate metabolic process	1	135.9×	0.007	GLB1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GLB1	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GLB1	1	4
TMPPE	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MIGALASTAT	4	GLB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GLB1	124	Binding:123, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GLB1	124

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MIGALASTAT	4	GLB1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GLB1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TMPPE

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TMPPE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.