HGSNAT Gene: Heparan-α-Glucosaminide N-Acetyltransferase
HGSNAT encodes the lysosomal enzyme responsible for acetyl-CoA-dependent acetylation of heparan sulfate, critical for its degradation; mutations cause mucopolysaccharidosis IIIC (Sanfilippo syndrome type C).
Gene Information Card
| Symbol | HGSNAT |
|---|---|
| Full Name | Heparan-α-Glucosaminide N-Acetyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 8p11.21 |
| NCBI Gene ID | 138050 ncbi.nlm.nih.gov/gene/138050 |
| Ensembl ID | ENSG00000104419 |
| UniProt ID | Q68CP4 |
| OMIM ID | 610453 |
| HGNC ID | 26527 |
| Aliases | MPS3C, TMEM76, FLJ12571 |
Description
The HGSNAT gene encodes heparan-α-glucosaminide N-acetyltransferase, a lysosomal transmembrane enzyme that catalyzes the acetylation of the terminal glucosamine residue of heparan sulfate using acetyl-CoA as a donor. This acetylation is a prerequisite for subsequent degradation by α-N-acetylglucosaminidase. Defects in HGSNAT lead to accumulation of heparan sulfate and cause mucopolysaccharidosis type IIIC (Sanfilippo syndrome type C), a severe autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucopolysaccharidosis type IIIC (Sanfilippo syndrome type C) | Loss-of-function mutations in HGSNAT impair heparan sulfate acetylation, leading to lysosomal accumulation of heparan sulfate and neurodegeneration. | ClinVar, OMIM #252930 |
| Mucopolysaccharidosis III (Sanfilippo syndrome) – general | HGSNAT mutations cause subtype C of MPS III, with identical clinical phenotype to other subtypes. | OMIM #252930, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Liver | 3.8 | Low |
| Kidney | 4.1 | Low |
| Lung | 2.9 | Low |
| Heart | 3.0 | Low |
| Skeletal muscle | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 4.5 | Embryonic kidney cell line |
| HeLa | 3.2 | Cervical carcinoma cell line |
| HepG2 | 3.9 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 5.0 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.234+1G>A | Splice donor | Unknown | Loss of function; associated with MPS IIIC |
| c.493C>T (p.Arg165*) | Nonsense | Unknown | Premature stop; loss of function |
| c.852-1G>C | Splice acceptor | Unknown | Loss of function |
| c.1129C>T (p.Arg377Trp) | Missense | Unknown | Likely loss of function; reduced enzyme activity |
Mutation functional classification
Loss of Function (LOF)
Most reported HGSNAT mutations (nonsense, frameshift, splice site, missense) result in complete or partial loss of enzymatic activity, leading to lysosomal heparan sulfate accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HGSNAT.
Dominant Negative (DN)
No dominant-negative mutations have been described; MPS IIIC is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • lysosome (GO:0005764) | • acyltransferase activity (GO:0016747) |
| • enzyme binding (GO:0019899) | • heparan sulfate proteoglycan catabolic process (GO:0030203) |
| • chondroitin sulfate metabolic process (GO:0030204) | • intracellular membrane-bounded organelle (GO:0043231) |
Pathways
• Glycosaminoglycan degradation (KEGG: hsa00531)
• Lysosome (KEGG: hsa04142)
• Heparan sulfate/heparin metabolism (Reactome: R-HSA-1638091)
Protein Summary
HGSNAT is a 635-amino acid lysosomal transmembrane protein with a single N-terminal transmembrane domain. It functions as a homodimer and uses acetyl-CoA to acetylate the terminal α-glucosamine residue of heparan sulfate, a critical step in its lysosomal degradation. The protein is ubiquitously expressed at low levels, with highest expression in brain and liver. Defects cause Sanfilippo syndrome type C.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HGSNAT Knockout HEK293 Cell Line | EDJ-KQ2968 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout A-549 Cell Line | EDJ-KQ24125 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout HeLa Cell Line | EDJ-KQ24127 | Human | 138050 | Details Get a Quote |
| HGSNAT Knockout HCT 116 Cell Line | EDJ-KQ22755 | Human | 138050 | Details Get a Quote |
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