NDST4: N-Deacetylase and N-Sulfotransferase 4
Key enzyme in heparan sulfate biosynthesis with implications in development and disease
Gene Information Card
| Symbol | NDST4 |
|---|---|
| Full Name | N-Deacetylase and N-Sulfotransferase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q26 |
| NCBI Gene ID | 64579 ncbi.nlm.nih.gov/gene/64579 |
| Ensembl ID | ENSG00000138653 |
| UniProt ID | Q9H3Q1 |
| OMIM ID | 607864 |
| HGNC ID | 7681 |
| Aliases | HSST4, NST4 |
Description
NDST4 encodes a bifunctional enzyme with both N-deacetylase and N-sulfotransferase activities, essential for the modification of heparan sulfate glycosaminoglycans. This enzyme catalyzes the removal of N-acetyl groups from N-acetylglucosamine residues and subsequent N-sulfation, a critical step in heparan sulfate biosynthesis. NDST4 is predominantly expressed in the brain and plays roles in cell signaling, development, and extracellular matrix interactions. Variants in NDST4 have been associated with neurodevelopmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder | Loss-of-function variants impair heparan sulfate modification, disrupting neuronal migration and synaptic signaling | ClinVar |
| Colorectal cancer | Somatic mutations and altered expression affect heparan sulfate-dependent growth factor signaling | COSMIC |
| Breast cancer | Reduced NDST4 expression correlates with tumor progression and metastasis | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 6.1 | Low |
| Liver | 3.2 | Not detected |
| Lung | 4.7 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 9.8 | Common expression system |
| MCF7 (breast cancer) | 4.1 | Reduced in cancer |
| HCT116 (colorectal cancer) | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375*) | Nonsense | <0.01% | Loss of function |
| c.1456G>A (p.Gly486Arg) | Missense | 0.02% | Impaired sulfotransferase activity |
| c.789_790del (p.Leu264fs) | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, reducing heparan sulfate N-sulfation.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • N-deacetylase activity (GO:0015019) | • N-sulfotransferase activity (GO:0015020) |
| • heparan sulfate proteoglycan biosynthetic process (GO:0015015) | • Golgi apparatus (GO:0005794) |
Pathways
• Heparan sulfate biosynthesis (Reactome: R-HSA-2022928)
• Glycosaminoglycan metabolism (KEGG: hsa00532)
Protein Summary
NDST4 is a 873-amino acid type II transmembrane protein localized to the Golgi apparatus. It contains an N-terminal cytoplasmic domain, a transmembrane domain, and a luminal catalytic domain with N-deacetylase and N-sulfotransferase activities. The enzyme modifies heparan sulfate chains by removing acetyl groups from GlcNAc residues and adding sulfate groups, influencing ligand binding and signaling. Structural studies indicate a conserved sulfotransferase domain with a 3'-phosphoadenosine-5'-phosphosulfate (PAPS) binding site.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NDST4 Knockout HEK293 Cell Line | EDJ-KQ51621 | Human | 64579 | Details Get a Quote |
| NDST4 Knockout HeLa Cell Line | EDJ-KQ57063 | Human | 64579 | Details Get a Quote |
| NDST4 Knockout A-549 Cell Line | EDJ-KQ65576 | Human | 64579 | Details Get a Quote |
| NDST4 Knockout HCT 116 Cell Line | EDJ-KQ74005 | Human | 64579 | Details Get a Quote |
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