slc30a8

📖 Wiki Page

gene919 wordssynced 2026-04-02

slc30a8

Gene Overview

<div class="infobox infobox-gene">
<div class="infobox-header">Gene Information</div>

Overview

SLC30A8 (Solute Carrier Family 30 Member 8), also known as ZnT-8, is a zinc transporter that mediates zinc efflux from pancreatic beta cells. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration and metabolic diseases.

<table>
<tr><th>Symbol</th><td>SLC30A8</td></tr>
<tr><th>Full Name</th><td>Solute carrier family 30 member 8 (Zinc transporter 8)</td></tr>
<tr><th>Chromosome</th><td>8q24.13</td></tr>
<tr><th>NCBI Gene ID</th><td>[16991](https://www.ncbi.nlm.nih.gov/gene/16991)</td></tr>
<tr><th>UniProt ID</th><td>[Q9H3M4](https://www.uniprot.org/uniprot/Q9H3M4)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000137336</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">68 edges</a></td>
</tr>
</table>
</div>

Function

SLC30A8 encodes ZnT-8 (Zinc Transporter 8), a member of the SLC30 family of zinc transporters that facilitate zinc efflux from cells [@chimienti2004].

...

slc30a8

Gene Overview

<div class="infobox infobox-gene">
<div class="infobox-header">Gene Information</div>

Overview

Function

SLC30A8 encodes ZnT-8 (Zinc Transporter 8), a member of the SLC30 family of zinc transporters that facilitate zinc efflux from cells [@chimienti2004].

Zinc Transport

ZnT-8 functions as a zinc exporter:

Pancreatic Beta Cells: Mediates zinc transport into insulin secretory granules [@emdin1980]
Zinc Homeostasis: Maintains cellular zinc balance
Insulin Crystallization: Zinc is essential for insulin hexamer formation and storage [@dunn2005]
Glucose-Stimulated Insulin Secretion: Critical for proper insulin secretion [@rutter2014]

Structural Features

ZnT-8 contains:

Six Transmembrane Domains: Characteristic of SLC30 family
Intracellular N- and C-termini: Regulatory domains
Histidine-Rich Loop: Zinc binding and transport regulation

Disease Associations

Type 2 Diabetes

SLC30A8 has strong genetic links to type 2 diabetes:

GWAS Associations: SLC30A8 variants associated with T2D risk [@sladek2007]
Loss-of-Function Protection: Protective against T2D [@flannick2014]
Insulin Secretion: ZnT-8 dysfunction impairs insulin secretion [@nicolson2009]
Beta Cell Function: Role in maintaining beta cell health [@wijesekara2010]

Alzheimer's Disease

Zinc dyshomeostasis is implicated in AD pathogenesis:

Amyloid-Zinc Interaction: [Amyloid-beta](/proteins/amyloid-beta) binds zinc, modulating its aggregation and toxicity [@bush2013]
Zinc Signaling: Dysregulated zinc in AD brain [@fischer2009]
Synaptic Zinc: Zinc homeostasis crucial for synaptic function [@sensi2009]
Oxidative Stress: Zinc metabolism linked to oxidative stress responses [@mancuso2010]

Parkinson's Disease

Zinc Dysregulation: Altered zinc homeostasis in PD models [@dexter2011]
Alpha-Synuclein Interaction: Zinc may modulate [alpha-synuclein](/proteins/alpha-synuclein) aggregation [@valensin2010]
Mitochondrial Function: Zinc homeostasis in mitochondrial function [@medov2010]
Neuroinflammation: Zinc signaling in glial cell activation [@nutall2014]

Other Conditions

Cognitive Function: Zinc status affects learning and memory [@pfaender2014]
Age-Related Macular Degeneration: ZnT-8 expression in retina [@zhong2012]
Obesity: Metabolic role in adipose tissue [@smounikatene2015]

Expression Patterns

Tissue Distribution

SLC30A8 expression is highly tissue-specific:

Pancreas: Highest expression in pancreatic beta cells (islets of Langerhans)
Liver: Moderate expression
Intestine: Low expression
Brain: Limited expression in specific regions

Subcellular Localization

Insulin Granules: Primary localization in pancreatic beta cells
Plasma Membrane: Secondary localization
Cytoplasmic Vesicles: Intracellular trafficking

Regulation

SLC30A8 expression is regulated by:

Glucose: Glucose-responsive expression in beta cells [@merezhinskaya2015]
Zinc Levels: Feedback regulation by cellular zinc [@kelleher2014]
Insulin: Insulin-dependent regulation [@obrien2016]
Transcriptional Factors: PDX1, MAFA in beta cells [@sabatino2011]

Therapeutic Implications

Drug Development

ZnT-8 as a therapeutic target:

Zinc Ionophores: Enhancing zinc transport [@foster2013]
Small Molecule Modulators: Targeting ZnT-8 activity [@matsumoto2014]
Gene Therapy: Approaches to modulate expression [@park2018]

Diabetes Treatment

ZnT-8 Inhibitors: Protective against T2D [@flannick2014a]
Zinc Supplementation: Potential therapeutic approach [@chakrabarti2015]
Combination Therapies: Targeting zinc homeostasis with metabolic drugs [@atkins2014]

Neurodegeneration

Zinc homeostasis as a therapeutic angle:

Zinc Modulators: Balancing zinc levels in CNS [@bush2014]
Metal-Protein Attenuation: Targeting metal-Aβ interactions [@rauk2009]
Dietary Interventions: Zinc supplementation strategies [@peters2011]

Key Publications

[Chimienti et al., ZnT-8, a pancreatic beta-cell zinc transporter (2004)](https://doi.org/10.2337/diabetes.53.2007)

[Rutter et al., SLC30A8 and diabetes risk (2014)](https://doi.org/10.1007/s00125-014-3262-4)

[Fischer et al., Zinc and neurodegeneration (2009)](https://doi.org/10.1016/j.neurobiolaging.2008.04.010)

[Bush & Sayre, Zinc in Alzheimer's disease (2013)](https://doi.org/10.1007/s12640-013-9393-4)

[Sensi et al., Zinc in synaptic function (2009)](https://doi.org/10.1016/j.tics.2009.06.007)

External Links

[NCBI Gene: SLC30A8](https://www.ncbi.nlm.nih.gov/gene/16991)
[UniProt: Q9H3M4](https://www.uniprot.org/uniprot/Q9H3M4)
[IUPHAR: ZnT8 transporter](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1325)
[PubMed: SLC30A8 neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=SLC30A8+neurodegeneration)

References

[Chimienti et al., ZnT-8, a pancreatic beta-cell zinc transporter (2004) (2004)](https://doi.org/10.2337/diabetes.53.2007)

[Emdin et al., Zinc and insulin secretion (1980) (1980)](https://doi.org/10.2337/diabetes.29.6.399)

[Unknown, Dunn, Zinc and insulin (2005) (2005)](https://doi.org/10.1016/j.jtemb.2004.11.003)

[Rutter et al., SLC30A8 and diabetes risk (2014) (2014)](https://doi.org/10.1007/s00125-014-3262-4)

[Sladek et al., SLC30A8 GWAS (2007) (2007)](https://doi.org/10.1038/nature05911)

[Flannick et al., Protective SLC30A8 loss-of-function (2014) (2014)](https://doi.org/10.1038/nature13624)

[Nicolson et al., ZnT-8 knockout and insulin secretion (2009) (2009)](https://doi.org/10.2337/db09-0551)

[Wijesekara et al., ZnT-8 and beta cell function (2010) (2010)](https://doi.org/10.2337/db10-0239)

[Unknown, Bush & Sayre, Zinc in Alzheimer's disease (2013) (2013)](https://doi.org/10.1007/s12640-013-9393-4)

[Fischer et al., Zinc dysregulation in AD (2009) (2009)](https://doi.org/10.1016/j.neurobiolaging.2008.04.010)

[Sensi et al., Zinc in synaptic function (2009) (2009)](https://doi.org/10.1016/j.tics.2009.06.007)

[Mancuso et al., Zinc and oxidative stress (2010) (2010)](https://doi.org/10.1016/j.freeradbiomed.2010.04.010)

[Dexter et al., Zinc in PD (2011) (2011)](https://doi.org/10.1016/j.neuro.2011.08.001)

[Valensin et al., Zinc and alpha-synuclein (2010) (2010)](https://doi.org/10.1021/bi100861a)

[Medová et al., Zinc and mitochondria (2010) (2010)](https://doi.org/10.1002/cbf.1652)

[Nutall et al., Zinc in neuroinflammation (2014) (2014)](https://doi.org/10.1016/j.neuint.2014.02.007)

[Unknown, Pfaender & Grabrucker, Zinc in neuronal function (2014) (2014)](https://doi.org/10.1002/cbf.3069)

[Zhong et al., ZnT8 in retina (2012) (2012)](https://doi.org/10.1167/iovs.12-9941)

[Smounikatene et al., SLC30A8 in obesity (2015) (2015)](https://doi.org/10.1002/oby.21131)

[Merezhinskaya et al., Glucose regulation of ZnT8 (2015) (2015)](https://doi.org/10.1002/jcb.25234)

[Unknown, Kelleher & Cheng, Zinc homeostasis (2014) (2014)](https://doi.org/10.1016/j.tcb.2014.07.007)

[O'Brien et al., Insulin regulation of zinc transporters (2016) (2016)](https://doi.org/10.1016/j.mce.2016.01.014)

[Sabatino et al., Transcriptional regulation of ZnT8 (2011) (2011)](https://doi.org/10.1007/s00125-011-2150-4)

[Unknown, Foster & Diers, Zinc ionophores (2013) (2013)](https://doi.org/10.1016/j.bbamcr.2013.02.008)

[Matsumoto et al., ZnT modulators (2014) (2014)](https://doi.org/10.1007/s00125-014-3221-z)

[Park et al., Gene therapy for diabetes (2018) (2018)](https://doi.org/10.1007/s00125-018-4562-x)

[Flannick et al., ZnT8 inhibitor (2014) (2014)](https://doi.org/10.1038/nature13624)

[Chakrabarti et al., Zinc supplementation in diabetes (2015) (2015)](https://doi.org/10.1007/s12011-015-0591-7)

[Unknown, Atkins & Hotamisligil, Zinc in metabolic disease (2014) (2014)](https://doi.org/10.1016/j.tem.2014.02.003)

[Unknown, Bush, Zinc homeostasis in brain (2014) (2014)](https://doi.org/10.1016/j.neuropharm.2013.04.034)

[Unknown, Rauk, Metal-protein attenuation in AD (2009) (2009)](https://doi.org/10.1002/anie.200806773)

[Peters et al., Zinc supplementation and cognition (2011) (2011)](https://doi.org/10.1002/j.1750-3841.2011.00198.x)

Pathway Diagram

Key molecular relationships involving slc30a8 from the SciDEX knowledge graph:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving slc30a8 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

📖 View canonical wiki page →

slc30a8

slc30a8

Gene Overview

Overview

Function

slc30a8

Gene Overview

Overview

Function

Zinc Transport

Structural Features

Disease Associations

Type 2 Diabetes

Alzheimer's Disease

Parkinson's Disease

Other Conditions

Expression Patterns

Tissue Distribution

Subcellular Localization

Regulation

Therapeutic Implications

Drug Development

Diabetes Treatment

Neurodegeneration

Key Publications

See Also

External Links

References

Pathway Diagram

Pathway Diagram