mucopolysaccharidosis type 3B

Summary

mucopolysaccharidosis type 3B (MONDO:0009656) is a disease caused by NAGLU (GenCC Definitive), with 2 cohort genes and 14 clinical trials. Top therapeutic interventions include lesinidase alfa.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: NAGLU (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,325
• Clinical trials: 14

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.2	Europe	Validated
Point prevalence	<1 / 1 000 000	0.014	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.42	Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.72	Portugal	Validated
Prevalence at birth	1-9 / 1 000 000	0.47	Australia	Validated
Prevalence at birth	<1 / 1 000 000	0.02	Czech Republic	Validated
Prevalence at birth	<1 / 1 000 000	0.05	Sweden	Validated
Prevalence at birth	<1 / 1 000 000	0.05	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	mucopolysaccharidosis type 3B
Mondo ID	MONDO:0009656
OMIM	252920
Orphanet	79270
DOID	DOID:0111394
ICD-11	117303909
NCIT	C84898
SNOMED CT	59990008
UMLS	C0086648
MedGen	88601
GARD	0007072
Is cancer (heuristic)	no

Also known as: MPS III B · MPS IIIB · MPS3B · MPSIIIB · Mucopoly-saccharidosis type 3B · mucopolysaccharidosis type 3B · mucopolysaccharidosis type IIIB · mucopolysaccharidosis, type IIIB · N-acetyl-alpha-glucosaminidase deficiency · Sanfilippo B · Sanfilippo syndrome B · Sanfilippo syndrome type B

Data availability: 1,325 ClinVar variants · 6 GenCC gene-disease records · 16 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › mucopolysaccharidosis type 3 › mucopolysaccharidosis type 3B

Related subtypes (3): mucopolysaccharidosis type 3A, mucopolysaccharidosis type 3C, mucopolysaccharidosis type 3D

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:

295 likely benign, 190 uncertain significance, 49 pathogenic, 28 likely pathogenic, 19 pathogenic/likely pathogenic, 16 conflicting classifications of pathogenicity, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066367	NM_000263.4(NAGLU):c.214_237dup (p.Ala72_Gly79dup)	LOC130060903	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068486	NM_000263.4(NAGLU):c.54_60dup (p.Ala21fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1068957	NM_000263.4(NAGLU):c.222_223del (p.Val75fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1071442	NM_000263.4(NAGLU):c.136del (p.Ala46fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1076543	NM_000263.4(NAGLU):c.71_87del (p.Asp24fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1382617	NM_000263.4(NAGLU):c.59dup (p.Ala21fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1454105	NM_000263.4(NAGLU):c.252_265del (p.Ala86fs)	LOC130060903	Pathogenic	criteria provided, single submitter
1456865	NM_000263.4(NAGLU):c.222_247del (p.Val75fs)	LOC130060903	Pathogenic	criteria provided, multiple submitters, no conflicts
1458683	NM_000263.4(NAGLU):c.3G>A (p.Met1Ile)	LOC130060903	Pathogenic	criteria provided, single submitter
1459501	NM_000263.4(NAGLU):c.192del (p.Tyr65fs)	LOC130060903	Pathogenic	criteria provided, multiple submitters, no conflicts
1569	NM_000263.4(NAGLU):c.142T>C (p.Phe48Leu)	LOC130060903	Pathogenic	criteria provided, single submitter
1067431	NM_000263.4(NAGLU):c.457G>A (p.Glu153Lys)	NAGLU	Pathogenic	criteria provided, multiple submitters, no conflicts
1067432	NM_000263.4(NAGLU):c.1081T>C (p.Trp361Arg)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068849	NM_000263.4(NAGLU):c.1453dup (p.Val485fs)	NAGLU	Pathogenic	criteria provided, single submitter
1069834	NC_000017.10:g.(?40690347)(40690783_?)del	NAGLU	Pathogenic	criteria provided, single submitter
1070682	NM_000263.4(NAGLU):c.454C>T (p.Arg152Ter)	NAGLU	Pathogenic	criteria provided, single submitter
1071435	NM_000263.4(NAGLU):c.432G>A (p.Trp144Ter)	NAGLU	Pathogenic	criteria provided, multiple submitters, no conflicts
1075574	NM_000263.4(NAGLU):c.1162C>T (p.Gln388Ter)	NAGLU	Pathogenic	criteria provided, single submitter
1076452	NM_000263.4(NAGLU):c.603G>A (p.Trp201Ter)	NAGLU	Pathogenic	criteria provided, single submitter
1323323	NM_000263.4(NAGLU):c.2045T>G (p.Leu682Arg)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324776	NM_000263.4(NAGLU):c.1675G>A (p.Asp559Asn)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343458	NM_000263.4(NAGLU):c.410_413del (p.Thr137fs)	NAGLU	Pathogenic	criteria provided, multiple submitters, no conflicts
1356379	NM_000263.4(NAGLU):c.640dup (p.Leu214fs)	NAGLU	Pathogenic	criteria provided, single submitter
1360395	NM_000263.4(NAGLU):c.1173dup (p.Thr392fs)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1362789	NM_000263.4(NAGLU):c.1460dup (p.His487fs)	NAGLU	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1376432	NM_000263.4(NAGLU):c.820del (p.Ser274fs)	NAGLU	Pathogenic	criteria provided, single submitter
1377108	NM_000263.4(NAGLU):c.1773del (p.Leu591_Leu592insTer)	NAGLU	Pathogenic	criteria provided, single submitter
1384177	NM_000263.4(NAGLU):c.713del (p.Met238fs)	NAGLU	Pathogenic	criteria provided, single submitter
1405883	NM_000263.4(NAGLU):c.387C>G (p.Tyr129Ter)	NAGLU	Pathogenic	criteria provided, single submitter
1409649	NM_000263.4(NAGLU):c.1570C>T (p.Gln524Ter)	NAGLU	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
NAGLU	Definitive	Autosomal recessive	mucopolysaccharidosis type 3B	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NAGLU	Orphanet:447964	Autosomal dominant Charcot-Marie-Tooth disease type 2V
NAGLU	Orphanet:79270	Sanfilippo syndrome type B
COASY	Orphanet:397725	COASY protein-associated neurodegeneration

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
NAGLU	HGNC:7632	ENSG00000108784	P54802	Alpha-N-acetylglucosaminidase	gencc,clinvar
COASY	HGNC:29932	ENSG00000068120	Q13057	Bifunctional coenzyme A synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NAGLU	Alpha-N-acetylglucosaminidase	Involved in the degradation of heparan sulfate.
COASY	Bifunctional coenzyme A synthase	Bifunctional enzyme that catalyzes the fourth step of the coenzyme A biosynthetic pathway, the adenylation of 4’-phosphopantetheine, and the fifth step, the phosphorylation of dephospho-CoA to CoA.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NAGLU	Enzyme (other)	yes	3.2.1.50	NAGLU, GH_hydrolase_sf, NAGLU_N
COASY	Kinase	yes	2.7.1.24	Depp_CoAkinase, Cyt_trans-like, Rossmann-like_a/b/a_fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
body of pancreas	1
mucosa of stomach	1
stromal cell of endometrium	1
lower esophagus mucosa	1
mucosa of transverse colon	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NAGLU	268	ubiquitous	marker	stromal cell of endometrium, body of pancreas, mucosa of stomach
COASY	280	ubiquitous	marker	parotid gland, mucosa of transverse colon, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COASY	3,273
NAGLU	1,200

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NAGLU	P54802	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COASY	Q13057	89.51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IIIB - Sanfilippo syndrome B	1	5710.0×	0.002	NAGLU
Mucopolysaccharidoses	1	951.7×	0.005	NAGLU
Coenzyme A biosynthesis	1	713.8×	0.005	COASY
Diseases of carbohydrate metabolism	1	407.9×	0.007	NAGLU
Heparan sulfate/heparin (HS-GAG) metabolism	1	271.9×	0.007	NAGLU
HS-GAG degradation	1	248.3×	0.007	NAGLU
Glycosaminoglycan metabolism	1	109.8×	0.014	NAGLU
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.023	NAGLU
Diseases of metabolism	1	40.2×	0.030	NAGLU
Disease	1	6.5×	0.162	NAGLU
Metabolism	1	5.8×	0.165	NAGLU

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 disaccharide	1	8426.0×	0.004	NAGLU
rod bipolar cell differentiation	1	4213.0×	0.004	NAGLU
ganglioside metabolic process	1	2106.5×	0.004	NAGLU
left ventricular cardiac muscle tissue morphogenesis	1	2106.5×	0.004	NAGLU
cone retinal bipolar cell differentiation	1	2106.5×	0.004	NAGLU
cytoplasm organization	1	1404.3×	0.004	NAGLU
heparin proteoglycan metabolic process	1	1404.3×	0.004	NAGLU
glycosaminoglycan metabolic process	1	1203.7×	0.004	NAGLU
inner ear receptor cell development	1	1203.7×	0.004	NAGLU
heparan sulfate proteoglycan catabolic process	1	936.2×	0.004	NAGLU
mitral valve morphogenesis	1	842.6×	0.004	NAGLU
retinal rod cell development	1	842.6×	0.004	NAGLU
microglia differentiation	1	766.0×	0.004	NAGLU
coenzyme A biosynthetic process	1	766.0×	0.004	COASY
cerebellar Purkinje cell layer development	1	766.0×	0.004	NAGLU
endothelium development	1	648.1×	0.005	NAGLU
amyloid precursor protein metabolic process	1	648.1×	0.005	NAGLU
collagen metabolic process	1	526.6×	0.005	NAGLU
locomotor rhythm	1	526.6×	0.005	NAGLU
superoxide metabolic process	1	495.6×	0.005	NAGLU
astrocyte activation	1	495.6×	0.005	NAGLU
obsolete vesicle tethering	1	495.6×	0.005	NAGLU
nerve development	1	468.1×	0.005	NAGLU
aorta morphogenesis	1	443.5×	0.005	NAGLU
hormone metabolic process	1	443.5×	0.005	NAGLU
middle ear morphogenesis	1	351.1×	0.005	NAGLU
exploration behavior	1	324.1×	0.006	NAGLU
microglial cell activation	1	312.1×	0.006	NAGLU
cardiac muscle cell development	1	312.1×	0.006	NAGLU
multicellular organismal-level iron ion homeostasis	1	290.6×	0.006	NAGLU

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COASY	1	2
NAGLU	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	COASY

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
COASY	10	Binding:10
NAGLU	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NAGLU	3.2.1.50	alpha-N-acetylglucosaminidase
COASY	2.7.1.24, 2.7.7.3	dephospho-CoA kinase, pantetheine-phosphate adenylyltransferase

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)
MOLIBRESIB	2	COASY

Druggability pyramid

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

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

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)
NAGLU	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE1/PHASE2	3
PHASE4	1
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05492799	PHASE4	ENROLLING_BY_INVITATION	Safety, Tolerability and Efficacy of ICV AX 250 Treatment in MPS IIIB -OLE
NCT07579910	PHASE3	NOT_YET_RECRUITING	Intracerebroventricular Tralesinidase Alfa in Children With Mucopolysaccharidosis Type IIIB
NCT02618512	PHASE1/PHASE2	TERMINATED	A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously
NCT02754076	PHASE1/PHASE2	COMPLETED	A Treatment Study of Mucopolysaccharidosis Type IIIB
NCT03300453	PHASE1/PHASE2	COMPLETED	Intracerebral Gene Therapy in Children With Sanfilippo Type B Syndrome
NCT03784287	PHASE2	UNKNOWN	A Treatment Extension Study of Mucopolysaccharidosis Type IIIB
NCT01509768	Not specified	COMPLETED	Natural History Study of Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)
NCT01873911	Not specified	COMPLETED	Neurobehavioral Phenotypes in MPS III
NCT02037880	Not specified	COMPLETED	Natural History Studies of Mucopolysaccharidosis III
NCT02090179	Not specified	COMPLETED	Evaluation of Blood Brain Barrier Integrity and Structural Abnormalities in MPS IIIB Patients Using Multimodal Magnetic Resonance Imaging
NCT02293382	Not specified	COMPLETED	A Retrospective Chart Review of Deceased Patients With Mucopolysaccharidosis Type IIIB
NCT02293408	Not specified	TERMINATED	Natural History Study to Characterise the Course of Disease Progression in Participants With Mucopolysaccharidosis Type IIIB
NCT02493998	Not specified	COMPLETED	A Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)
NCT03227042	Not specified	UNKNOWN	A Prospective Natural History Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LESINIDASE ALFA	2	1