SLC17A5 Gene

SLC17A5 Gene

Introduction

Slc17A5 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@sialin2020]
title: SLC17A5 [@alphasynuclein2021]
--- [@lysosomal2019]

<div class="infobox infobox-gene"> [@slca2018]
<table> [@sialidosis2020]
<tr><th colspan="2" style="background:#f8f9fa; text-align:center;">SLC17A5 - Solute Carrier Family 17 Member 5</th></tr> [@lysosomal2022]
<tr><td><b>Gene Symbol</b></td><td>SLC17A5</td></tr> [@sialic2021]
<tr><td><b>Full Name</b></td><td>Solute Carrier Family 17 Member 5 (Sialin)</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>6q13</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[10228](https://www.ncbi.nlm.nih.gov/gene/10228)</td></tr>
<tr><td><b>OMIM</b></td><td>[604716](https://www.omim.org/entry/604716)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>[ENSG00000183040](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000183040)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9NRX3](https://www.uniprot.org/uniprot/Q9NRX3)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Sialidosis](/diseases/sialidosis), Infantile Sialic Acid Storage Disease</td></tr>
<tr><td><b>Protein</b></td><td>[SLC17A5 Protein](/proteins/slc17a5-protein)</td></tr>
</table>
</div>

Overview

SLC17A5 Gene

Introduction

Slc17A5 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@sialin2020]
title: SLC17A5 [@alphasynuclein2021]
--- [@lysosomal2019]

<div class="infobox infobox-gene"> [@slca2018]
<table> [@sialidosis2020]
<tr><th colspan="2" style="background:#f8f9fa; text-align:center;">SLC17A5 - Solute Carrier Family 17 Member 5</th></tr> [@lysosomal2022]
<tr><td><b>Gene Symbol</b></td><td>SLC17A5</td></tr> [@sialic2021]
<tr><td><b>Full Name</b></td><td>Solute Carrier Family 17 Member 5 (Sialin)</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>6q13</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[10228](https://www.ncbi.nlm.nih.gov/gene/10228)</td></tr>
<tr><td><b>OMIM</b></td><td>[604716](https://www.omim.org/entry/604716)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>[ENSG00000183040](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000183040)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9NRX3](https://www.uniprot.org/uniprot/Q9NRX3)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Sialidosis](/diseases/sialidosis), Infantile Sialic Acid Storage Disease</td></tr>
<tr><td><b>Protein</b></td><td>[SLC17A5 Protein](/proteins/slc17a5-protein)</td></tr>
</table>
</div>

Overview

The SLC17A5 (Solute Carrier Family 17 Member 5) gene encodes sialin, a lysosomal membrane protein that functions as a sialic acid transporter and anion channel. Sialin is essential for maintaining lysosomal homeostasis by exporting sialic acid (N-acetylneuraminic acid) from lysosomes into the cytoplasm. Mutations in SLC17A5 cause severe lysosomal storage disorders known as sialidosis and infantile sialic acid storage disease (ISSD), while dysregulation is implicated in Alzheimer's disease, Parkinson's disease, and various metabolic conditions.

Gene Structure

The SLC17A5 gene is located on chromosome 6q13 and encodes a protein of 495 amino acids. The gene structure includes:

• Exon count: 14 exons spanning approximately 25 kb
• Promoter region: Contains regulatory elements for tissue-specific expression
• Coding sequence: Encodes a polytopic membrane protein with 10-12 transmembrane domains

Normal Function

Sialic Acid Transport

Sialin functions as a proton-coupled sialic acid symporter:

• Lysosomal export: Exports sialic acid from lysosomes using the proton gradient as energy source[@sialin2019]
• Substrate specificity: Transports N-acetylneuraminic acid and related sialic acids
• Anion channel activity: Also functions as a voltage-gated anion channel

Glycoconjugate Recycling

Sialin enables recycling of sialylated glycoconjugates:

• Sialic acid recovery: Retrieves sialic acid from degraded glycoproteins and glycolipids
• Glycoprotein resialylation: Provides substrate for resialylation of newly synthesized proteins
• Lysosomal metabolism: Prevents accumulation of sialic acid that would cause lysosomal swelling

Neurotransmitter Transport

In [neurons](/entities/neurons), sialin participates in:

• Glutamate transport: Transports glutamate, modulating excitatory neurotransmission
• Aspartate transport: Contributes to excitatory amino acid homeostasis
• Vesicular function: Affects synaptic glycoprotein sialylation and function

Expression Pattern

SLC17A5 shows broad expression:

• High expression: Brain (particularly basal ganglia, [cortex](/brain-regions/cortex), hippocampus), liver, kidney
• Moderate expression: Lung, heart, skeletal muscle
• Cellular localization: Primarily lysosomal membrane; also plasma membrane in some cell types

Role in Neurodegeneration

Alzheimer's Disease

Sialin dysfunction contributes to AD through multiple mechanisms:

Parkinson's Disease

In Parkinson's disease, sialin plays important roles:

Sialidosis and ISSD

SLC17A5 mutations cause two related lysosomal storage disorders:

• Cherry-red macula
• Progressive myoclonus epilepsy
• Developmental regression
• Coarse facial features

• Severe early-onset neurodegeneration
• Organomegaly (hepatosplenomegaly)
• Failure to thrive
• Early mortality

Therapeutic Implications

Targeting sialin offers therapeutic potential:

• Gene therapy: AAV-mediated SLC17A5 delivery to neurons
• Enzyme replacement: Although challenging, approaches to restore sialin function
• Substrate reduction therapy: Reducing sialic acid synthesis to decrease lysosomal burden
• Pharmacological chaperones: Small molecules to stabilize mutant sialin

See Also

• [SLC17A5 Protein](/proteins/slc17a5-protein)
• [Lysosomal Degradation](/mechanisms/lysosomal-degradation)
• [Sialic Acid Metabolism](/mechanisms/sialic-acid-metabolism)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Sialidosis](/diseases/sialidosis)

Background

The study of Slc17A5 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

Pathway Diagram

The following diagram shows the key molecular relationships involving SLC17A5 Gene discovered through SciDEX knowledge graph analysis: