mucopolysaccharidosis type 3C

Summary

mucopolysaccharidosis type 3C (MONDO:0009657) is a disease caused by HGSNAT (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: HGSNAT (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,243
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	5	Europe	Validated
Point prevalence	<1 / 1 000 000	0.0004	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.21	Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.12	Portugal	Validated
Prevalence at birth	<1 / 1 000 000	0.07	Australia	Validated
Prevalence at birth	1-9 / 1 000 000	0.42	Czech Republic	Validated
Prevalence at birth	1-9 / 1 000 000	0.34	Sweden	Validated
Prevalence at birth	<1 / 1 000 000	0.015	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	mucopolysaccharidosis type 3C
Mondo ID	MONDO:0009657
OMIM	252930
Orphanet	79271
DOID	DOID:0111393
ICD-11	1755913480
NCIT	C84899
SNOMED CT	75238000
UMLS	C0086649
MedGen	39477
GARD	0007073
Is cancer (heuristic)	no

Also known as: Acetyl-CoA alpha-glucosaminide n-acetyltransferase deficiency · heparan-alpha-glucosaminide N-acetyltransferase deficiency · HGSNAT deficiency · MPS III C · MPS IIIC · MPS3C · MPSIIIC · Mucopoly-saccharidosis type 3C · mucopolysaccharidosis type 3C · mucopolysaccharidosis type IIIC · mucopolysaccharidosis, type IIIC · Sanfilippo C · Sanfilippo syndrome type C

Data availability: 1,243 ClinVar variants · 6 GenCC gene-disease records · 18 cell lines.

Disease family

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

Related subtypes (3): mucopolysaccharidosis type 3A, mucopolysaccharidosis type 3B, 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:

336 likely benign, 185 uncertain significance, 30 pathogenic, 20 likely pathogenic, 16 conflicting classifications of pathogenicity, 6 benign, 6 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069082	NM_152419.3(HGSNAT):c.1508dup (p.Leu504fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1073137	NM_152419.3(HGSNAT):c.376G>T (p.Glu126Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1074147	NM_152419.3(HGSNAT):c.1348del (p.Asp450fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1075807	NM_152419.3(HGSNAT):c.682_740del (p.Pro228fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1076291	NM_152419.3(HGSNAT):c.884_885insTATTTTTTTTTATTTTTTTNNNNNNNNNNTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGATCTTCCATTTTTCT (p.Leu295_Ser296insIlePhePheTyrPhePheXaaXaaXaaXaaLeuAlaArgMetValSerIleSerTer)	HGSNAT	Pathogenic	criteria provided, single submitter
1076551	NM_152419.3(HGSNAT):c.133dup (p.Arg45fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1076934	NM_152419.3(HGSNAT):c.1054_1055insATCAATTTCTAATGGGATTTCCAGAGTTGAAAAAGACAAATATTCAGCTTTAGGAAGCACAGTTGAGTCCTGAGCAGTACAAATAAAAATATAGGCTGGGCACAGTGGCTCACATGTGTAATCCCAGCACTTTCGGAGGCTGAGGTGGGTGGATTGCTGGAGTCCAGCAGTTTGAAAACAGCCTGAGCAACATGGCAAGACCCCATCTCTACAAAAAATACAACAATTATCCGGGCATGGTGGCACAAGCCCGTAGTCCCAGCTACTCAGGAAGCTGAGGTGGATCGCTTGAGCCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCACACCATTGCACTCCACACTGAATGACAGAGTGAGACTGTCTTAATAAAAAATATGAGTCAGCGTATAAGTTAAAAGGAGTTTTAAAAGATACTAATCCAAAAGAAGGCAGAAAAGGAGAAACATAATAGACTTACCAGCCCAATTTAAAAGTCAGGGATTATAAACATGAATTGAAGAAGTGAGACCCAGTTA (p.Leu352delinsTyrGlnPheLeuMetGlyPheProGluLeuLysLysThrAsnIleGlnLeuTer)	HGSNAT	Pathogenic	criteria provided, single submitter
1230	NM_152419.3(HGSNAT):c.493+1G>A	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1231	NM_152419.3(HGSNAT):c.1345dup (p.Asp449fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1232	NM_152419.3(HGSNAT):c.848C>T (p.Pro283Leu)	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1233	NM_152419.3(HGSNAT):c.962T>G (p.Leu321Ter)	HGSNAT	Pathogenic	no assertion criteria provided
1235	NM_152419.3(HGSNAT):c.525dup (p.Val176fs)	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1236	NM_152419.3(HGSNAT):c.372-2A>G	HGSNAT	Pathogenic	criteria provided, multiple submitters, no conflicts
1238	NM_152419.3(HGSNAT):c.1553C>T (p.Ser518Phe)	HGSNAT	Pathogenic	criteria provided, single submitter
1352962	NM_152419.3(HGSNAT):c.719del (p.Leu240fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1374201	NM_152419.3(HGSNAT):c.1323C>A (p.Tyr441Ter)	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1412507	NM_152419.3(HGSNAT):c.87_100dup (p.Gln34fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1453420	NM_152419.3(HGSNAT):c.1245C>A (p.Cys415Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1453457	NM_152419.3(HGSNAT):c.1464+1del	HGSNAT	Pathogenic	criteria provided, single submitter
1453856	NM_152419.3(HGSNAT):c.781G>T (p.Gly261Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
1455195	NM_152419.3(HGSNAT):c.1610del (p.Leu537fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1458656	NC_000008.10:g.(?43024296)(43024405_?)del	HGSNAT	Pathogenic	criteria provided, single submitter
1458765	NM_152419.3(HGSNAT):c.1034_1049del (p.Ile345fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1459479	NC_000008.10:g.(?42977230)(43002226_?)del	HGSNAT	Pathogenic	criteria provided, single submitter
1492894	NM_152419.3(HGSNAT):c.118+1G>A	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1502696	NM_152419.3(HGSNAT):c.1543-2A>G	HGSNAT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1977688	NM_152419.3(HGSNAT):c.1691dup (p.Leu566fs)	HGSNAT	Pathogenic	criteria provided, single submitter
1992944	NM_152419.3(HGSNAT):c.1139del (p.Cys380fs)	HGSNAT	Pathogenic	criteria provided, single submitter
2002352	NM_152419.3(HGSNAT):c.244C>T (p.Gln82Ter)	HGSNAT	Pathogenic	criteria provided, single submitter
2007566	NM_152419.3(HGSNAT):c.10del (p.Ala4fs)	HGSNAT	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 2 · 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
HGSNAT	Definitive	Autosomal recessive	mucopolysaccharidosis type 3C	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HGSNAT	Orphanet:791	Retinitis pigmentosa
HGSNAT	Orphanet:79271	Sanfilippo syndrome type C

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
HGSNAT	HGNC:26527	ENSG00000165102	Q68CP4	Heparan-alpha-glucosaminide N-acetyltransferase	gencc,clinvar
FNTA	HGNC:3782	ENSG00000168522	P49354	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HGSNAT	Heparan-alpha-glucosaminide N-acetyltransferase	Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.
FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex.

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
Enzyme (other)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HGSNAT	Enzyme (other)	yes	2.3.1.78	HGSNAT_cat
FNTA	Enzyme (other)	yes	2.5.1.58	Prenyl_trans_a

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
cervix squamous epithelium	1
mucosa of stomach	1
right uterine tube	1
esophagus squamous epithelium	1
gingival epithelium	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HGSNAT	287	ubiquitous	marker	mucosa of stomach, right uterine tube, cervix squamous epithelium
FNTA	298	ubiquitous	marker	esophagus squamous epithelium, gingival epithelium, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FNTA	1,080
HGSNAT	863

Intra-cohort edges

A	B	Sources
FNTA	HGSNAT	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FNTA	P49354	14
HGSNAT	Q68CP4	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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 IIIC - Sanfilippo syndrome C	1	5710.0×	0.001	HGSNAT
GBP-mediated host defense	1	519.1×	0.007	FNTA
HS-GAG degradation	1	248.3×	0.007	HGSNAT
Apoptotic cleavage of cellular proteins	1	237.9×	0.007	FNTA
RAS processing	1	237.9×	0.007	FNTA
Inactivation, recovery and regulation of the phototransduction cascade	1	158.6×	0.008	FNTA
Potential therapeutics for SARS	1	57.1×	0.020	FNTA
Neutrophil degranulation	1	11.5×	0.085	HGSNAT

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
peptide pheromone maturation	1	8426.0×	0.001	FNTA
protein farnesylation	1	2808.7×	0.002	FNTA
protein geranylgeranylation	1	1404.3×	0.002	FNTA
regulation of microtubule-based movement	1	1404.3×	0.002	FNTA
heparan sulfate proteoglycan catabolic process	1	936.2×	0.002	HGSNAT
skeletal muscle acetylcholine-gated channel clustering	1	936.2×	0.002	FNTA
positive regulation of skeletal muscle acetylcholine-gated channel clustering	1	936.2×	0.002	FNTA
lysosomal transport	1	351.1×	0.004	HGSNAT
protein complex oligomerization	1	337.0×	0.004	HGSNAT
positive regulation of Rac protein signal transduction	1	324.1×	0.004	FNTA
Rac protein signal transduction	1	280.9×	0.004	FNTA
transforming growth factor beta receptor signaling pathway	1	79.5×	0.013	FNTA

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
FNTA	CORTISONE ACETATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FNTA	6	4
HGSNAT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CORTISONE ACETATE	4	FNTA
LONAFARNIB	4	FNTA
TIPIFARNIB	3	FNTA
L-778123 FREE BASE	1	FNTA
GGTI-2418	1	FNTA
BMS-214662	1	FNTA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
FNTA	513	Binding:438, Functional:75

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HGSNAT	2.3.1.78	heparan-alpha-glucosaminide N-acetyltransferase
FNTA	2.5.1.58, 2.5.1.59	protein farnesyltransferase, protein geranylgeranyltransferase type I

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FNTA	513

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

6 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)
CORTISONE ACETATE	4	FNTA
LONAFARNIB	4	FNTA
TIPIFARNIB	3	FNTA
L-778123 FREE BASE	1	FNTA
GGTI-2418	1	FNTA
BMS-214662	1	FNTA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FNTA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HGSNAT
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)
HGSNAT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05825131	Not specified	RECRUITING	Natural History Study of Participants With Sanfilippo Syndrome Type IIIC