HS3ST2 Gene

HS3ST2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">hs3st2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HS3ST2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Heparan Sulfate-Glucosamine 3-Sulfotransferase 2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">Entrez ID</td>
<td>9956</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5P9</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>3-OST-2, 3OST2</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>Relationship</td>
</tr>
<tr>
<td class="label">[TGFB1](/genes/tgfb1)</td>
<td>Regulator of HS3ST2 expression</td>
</tr>
<tr>
<td class="label">[MAPT](/genes/mapt)</td>
<td>Target of 3S-HS-modulated pathology</td>
</tr>
<tr>
<td class="label">[SMAD2](/genes/smad2)</td>
<td>TGFβ signaling intermediate</td>
</tr>
<tr>
<td class="label">[SMAD3](/genes/smad3)</td>
<td>TGFβ signaling intermediate</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

HS3ST2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">hs3st2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HS3ST2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Heparan Sulfate-Glucosamine 3-Sulfotransferase 2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">Entrez ID</td>
<td>9956</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5P9</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>3-OST-2, 3OST2</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>Relationship</td>
</tr>
<tr>
<td class="label">[TGFB1](/genes/tgfb1)</td>
<td>Regulator of HS3ST2 expression</td>
</tr>
<tr>
<td class="label">[MAPT](/genes/mapt)</td>
<td>Target of 3S-HS-modulated pathology</td>
</tr>
<tr>
<td class="label">[SMAD2](/genes/smad2)</td>
<td>TGFβ signaling intermediate</td>
</tr>
<tr>
<td class="label">[SMAD3](/genes/smad3)</td>
<td>TGFβ signaling intermediate</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

HS3ST2 (Heparan Sulfate-Glucosamine 3-Sulfotransferase 2) is a gene encoding an enzyme critical for the biosynthesis of 3-O-sulfated heparan sulfate (3S-HS), a specialized form of heparan sulfate proteoglycans (HSPGs). Recent research has identified HS3ST2 as a key modulator of tau pathology in Alzheimer's disease and related tauopathies through the TGFβ1-HS3ST2-tau signaling axis (PMID: [41810327](https://pubmed.ncbi.nlm.nih.gov/41810327/)).

Gene Information

Protein Structure and Function

Enzyme Activity

HS3ST2 catalyzes the transfer of sulfate groups to the 3-O position of heparan sulfate chains, producing 3-O-sulfated heparan sulfate (3S-HS). This specific sulfation pattern creates binding sites for various proteins, including:

• Tau protein ([MAPT](/genes/mapt))
• Growth factors
• Morphogens
• Viral entry proteins

Expression Pattern

• Brain expression: Expressed in neurons, particularly hippocampal neurons
• Cellular localization: Located on the neuronal cell surface
• Regulation: Upregulated by [TGFβ1](/genes/tgfb1) signaling

Role in Alzheimer's Disease

The TGFβ1-HS3ST2-tau Axis

HS3ST2 plays a central role in the recently characterized TGFβ1-HS3ST2-tau signaling axis:

Pathological Implications

Elevated HS3ST2 expression in AD brain leads to:

• Increased 3S-HS production: Creates pathological heparan sulfate environment
• Enhanced tau binding: 3S-HS serves as docking site for pathological tau
• Accelerated tau aggregation: Facilitates tau oligomerization and propagation
• Synaptic toxicity: Contributes to synaptic loss and cognitive decline

Therapeutic Target

Knockdown of HS3ST2:

• Reduces 3S-HS levels significantly
• Decreases tau phosphorylation at multiple epitopes
• Reduces tau oligomerization
• Improves synaptic integrity in hippocampal neurons

Relationship to Other Genes

Clinical Significance

Biomarker Potential

• HS3ST2 expression may serve as a biomarker for tau pathology severity
• 3S-HS levels in CSF potentially measurable
• Correlates with synaptic dysfunction markers

Therapeutic Development

• Small molecule HS3ST2 inhibitors
• RNA interference approaches
• Antibody-based therapies targeting 3S-HS
• Gene therapy to reduce HS3ST2 expression

Research Highlights

Key Studies

References

Related Pages

• [TGFβ1 Gene](/genes/tgfb1)
• [MAPT Gene](/genes/mapt)
• [TGFβ1-HS3ST2-tau Signaling Axis](/mechanisms/tgf-beta-hs3st2-tau-axis)
• [Tau Pathology Pathway](/mechanisms/tau-pathology)
• [Synaptic Dysfunction in AD](/mechanisms/synaptic-dysfunction-hypothesis)