SLC30A1

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SLC30A1

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SLC30A1

<table class="infobox-table">
<tr><th>Gene Symbol</th><td>SLC30A1</td></tr>
<tr><th>Full Name</th><td>Solute Carrier Family 30 Member 1 (Zinc Transporter 1)</td></tr>
<tr><th>Chromosomal Location</th><td>1q21.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[7779](https://www.ncbi.nlm.nih.gov/gene/7779)</td></tr>
<tr><th>OMIM</th><td>[604949](https://www.omim.org/entry/604949)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000170370](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170370)</td></tr>
<tr><th>UniProt</th><td>[Q9Y5W5](https://www.uniprot.org/uniprot/Q9Y5W5)</td></tr>
<tr><th>Protein Length</th><td>501 amino acids</td></tr>
<tr><th>Protein Family</th><td>SLC30 (ZnT) family</td></tr>
<tr><th>Expression</th><td>Ubiquitous (highest in brain, intestine, kidney)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

SLC30A1 (also known as ZnT1) encodes the first identified member of the solute carrier family 30, a group of zinc transporters responsible for effluxing zinc from the cytoplasm into the extracellular space or into intracellular organelles. ZnT1 was discovered as the mammalian homologue of the yeast zinc transporter ZRT1 and is essential for maintaining cellular zinc homeostasis [1](https://pubmed.ncbi.nlm.nih.gov/9009230/).

...

SLC30A1

<table class="infobox-table">
<tr><th>Gene Symbol</th><td>SLC30A1</td></tr>
<tr><th>Full Name</th><td>Solute Carrier Family 30 Member 1 (Zinc Transporter 1)</td></tr>
<tr><th>Chromosomal Location</th><td>1q21.3</td></tr>
<tr><th>NCBI Gene ID</th><td>[7779](https://www.ncbi.nlm.nih.gov/gene/7779)</td></tr>
<tr><th>OMIM</th><td>[604949](https://www.omim.org/entry/604949)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000170370](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170370)</td></tr>
<tr><th>UniProt</th><td>[Q9Y5W5](https://www.uniprot.org/uniprot/Q9Y5W5)</td></tr>
<tr><th>Protein Length</th><td>501 amino acids</td></tr>
<tr><th>Protein Family</th><td>SLC30 (ZnT) family</td></tr>
<tr><th>Expression</th><td>Ubiquitous (highest in brain, intestine, kidney)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

SLC30A1 (also known as ZnT1) encodes the first identified member of the solute carrier family 30, a group of zinc transporters responsible for effluxing zinc from the cytoplasm into the extracellular space or into intracellular organelles. ZnT1 was discovered as the mammalian homologue of the yeast zinc transporter ZRT1 and is essential for maintaining cellular zinc homeostasis [1](https://pubmed.ncbi.nlm.nih.gov/9009230/).

ZnT1 plays a critical role in protecting cells from zinc toxicity while also ensuring adequate zinc supply for essential cellular functions. In the brain, ZnT1 is expressed in neurons, astrocytes, and the blood-brain barrier, where it contributes to zinc homeostasis in the [central nervous system](/brain-regions/central-nervous-system) [2](https://pubmed.ncbi.nlm.nih.gov/10831576/). Dysregulation of ZnT1 has been implicated in the pathogenesis of [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and other neurodegenerative disorders [3](https://doi.org/10.1016/j.neurobiolaging.2019.01.011).

Molecular Function

Zinc Transport Mechanism

ZnT1 catalyzes zinc export from the cytoplasm using a proton gradient-driven antiport mechanism. The transporter couples zinc efflux to the influx of protons (or other cations), utilizing the energy stored in the transmembrane proton gradient [4](https://doi.org/10.1074/jbc.M001555200).

The transport cycle involves:

Zinc binding: Zn^2+ binds to the transporter from the cytoplasm

Proton coupling: H+ binds from the extracellular or luminal side

Exchange: Zinc and protons are exchanged across the membrane

Recycling: The transporter resets for another cycle

Structure

ZnT1 belongs to the CDF (cation diffusion facilitator) family, characterized by:

Six transmembrane domains: Form the transport channel
N- and C-terminal tails: Located in the cytoplasm
Histidine-rich loop: Between TM4 and TM5 (involved in zinc binding)
Dimerization: Functions as a homodimer [5](https://doi.org/10.1074/jbc.M106414200)

Key structural features include:

Zinc binding sites in the transmembrane helices
Proton coupling residues (Asp, Glu) in the membrane domain
Dimerization interface for functional activity

Regulation

ZnT1 expression is regulated at multiple levels:

Transcriptional regulation:

Zinc-dependent: MTF-1 (metal-responsive transcription factor-1) activates transcription under zinc deficiency
Cellular zinc status: Zinc-responsive promoter elements control expression
Hormonal regulation: Glucocorticoids and other hormones affect expression

Post-translational regulation:

Phosphorylation: Casein kinase 2 (CK2) phosphorylates ZnT1, modulating its activity
Trafficking: Subcellular localization affects transport activity
Protein-protein interactions: Interaction with metallothioneins modulates function

Tissue Distribution and Expression

Brain Expression

In the central nervous system, ZnT1 is expressed in:

| Cell Type | Location | Function |
|-----------|----------|----------|
| Neurons | Cortex, Hippocampus, Cerebellum | Zinc homeostasis |
| Astrocytes | Throughout brain | Zinc buffering |
| Microglia | Activated regions | Inflammatory response |
| Endothelial cells | BBB | Zinc transport into brain |

In the [hippocampus](/brain-regions/hippocampus), ZnT1 is particularly abundant in CA1 pyramidal neurons and dentate gyrus granule cells, where zinc signaling is important for synaptic transmission and plasticity [6](https://pubmed.ncbi.nlm.nih.gov/11882654/).

Peripheral Tissues

High expression is also found in:

Intestine: Epithelial cells (zinc absorption)
Kidney: Proximal tubules (zinc reabsorption)
Pancreas: Islet cells (zinc handling in insulin secretion)
Liver: Hepatocytes (systemic zinc homeostasis)
Placenta: Trophoblast cells (zinc transport to fetus)

Biological Roles

Zinc Homeostasis

ZnT1 is the primary exporter of cellular zinc, playing a central role in:

Protecting cells from zinc toxicity
Maintaining cytosolic zinc concentrations
Enabling zinc secretion into extracellular fluids
Facilitating zinc transport across barriers (BBB, intestinal epithelium)

Synaptic Zinc Signaling

In the brain, ZnT1 participates in synaptic zinc dynamics:

Regulates synaptic zinc concentrations
Modulates NMDA receptor activity
Affects GABAergic signaling
Influences long-term potentiation and memory [7](https://doi.org/10.1016/j.neuropharm.2018.03.023)

Metallothionein Interaction

ZnT1 works in concert with metallothioneins (MTs):

MTs buffer cytosolic zinc
ZnT1 exports excess zinc
Together they maintain zinc homeostasis under stress conditions

Disease Associations

Alzheimer's Disease

ZnT1 dysfunction may contribute to Alzheimer's disease pathogenesis through several mechanisms [3](https://doi.org/10.1016/j.neurobiolaging.2019.01.011):

Amyloid metabolism: Zinc is required for [amyloid precursor protein](/proteins/app) processing. ZnT1 alterations may affect Aβ production and aggregation:

Zinc promotes amyloidogenic APP cleavage
ZnT1-mediated zinc export may modulate this process
Altered zinc homeostasis in AD brain may drive plaque formation

Tau pathology: Zinc homeostasis affects tau phosphorylation:

Zinc activates several kinases involved in tau hyperphosphorylation
ZnT1 dysfunction may contribute to neurofibrillary tangle formation

Synaptic dysfunction: Zinc is crucial for synaptic plasticity:

ZnT1 regulates synaptic zinc affecting LTP
Dysregulation contributes to cognitive decline

Neuroinflammation: Zinc modulates neuroinflammation:

ZnT1 in microglia affects cytokine production
Altered zinc signaling promotes inflammatory responses

Parkinson's Disease

ZnT1 involvement in Parkinson's disease includes [8](https://doi.org/10.1016/j.neurobiolaging.2020.02.008):

Dopaminergic neuron vulnerability: Zinc homeostasis in substantia nigra:

ZnT1 expression is altered in PD brain
Zinc dysregulation may sensitize neurons to toxins

Alpha-synuclein aggregation: Zinc affects [alpha-synuclein](/proteins/alpha-synuclein) aggregation:

Zinc promotes α-synuclein oligomerization
ZnT1 dysfunction may contribute to Lewy body formation

Mitochondrial dysfunction: Zinc homeostasis and mitochondrial health:

Zinc modulates mitochondrial function
ZnT1 dysfunction may exacerbate mitochondrial deficits

Amyotrophic Lateral Sclerosis (ALS)

ZnT1 expression is altered in ALS:

Motor neurons show dysregulated zinc homeostasis
ZnT1 modifications affect SOD1 aggregation (in SOD1-linked ALS)
Therapeutic targeting of zinc transport is being explored [9](https://doi.org/10.1093/brain/awz123)

Autism Spectrum Disorders

ZnT1 mutations or dysregulation have been reported in ASD:

Zinc homeostasis is important for neuronal development
ZnT1 variants may contribute to synaptic dysfunction
Altered zinc metabolism is a consistent finding in ASD patients [10](https://pubmed.ncbi.nlm.nih.gov/29487654/)

Intellectual Disability

Rare SLC30A1 variants cause:

Zinc deficiency syndrome: Impaired zinc transport
Neurodevelopmental delay: Cognitive impairment
Growth retardation: Systemic effects

Neurodegeneration Mechanisms

Zinc Toxicity

While zinc is essential, excess zinc is neurotoxic:

ZnT1 deficiency leads to zinc accumulation
Zinc triggers mitochondrial dysfunction
Oxidative stress results from zinc overload
Apoptosis is induced by excessive zinc [11](https://doi.org/10.1016/j.neurobiolaging.2018.06.020)

Oxidative Stress

ZnT1 dysfunction contributes to oxidative stress:

Impaired zinc homeostasis affects antioxidant systems
Zinc is required for antioxidant enzyme function
Dysregulation leads to ROS accumulation

Synaptic Failure

Synaptic zinc homeostasis is critical for:

Neurotransmitter release
Receptor function
Plasticity mechanisms
ZnT1 dysfunction disrupts these processes

Protein Aggregation

Zinc homeostasis affects aggregation of:

Amyloid-beta in AD
Alpha-synuclein in PD
TDP-43 in ALS
Huntingtin in HD

Therapeutic Implications

Small Molecule Modulators

Developing zinc transport modulators for neurodegeneration:

Zinc ionophores: Facilitate zinc transport across membranes
ZnT1 agonists: Enhance zinc export capacity
Zinc chelators: Reduce zinc accumulation in disease states

Gene Therapy

Viral vector-mediated ZnT1 expression:

AAV-ZnT1 for protecting neurons
Targeting specific brain regions
Combination with other therapeutic genes

Nutritional Intervention

Zinc supplementation/expletion strategies:

Careful titration required (both deficiency and excess are harmful)
Monitoring zinc homeostasis in patients
Personalized approaches based on genotype

Interaction Network

ZnT1 interacts with:

Metallothioneins (MT1, MT2): Zinc buffering
MTF-1: Transcriptional regulation
Zinc sensors (ZIP family): Coordinated zinc homeostasis
Ion channels: Cross-talk with other transporters
Signaling molecules: Kinases and phosphatases

Animal Models

ZnT1 knockout mice:

Embryonic lethality (essential for development)
Conditional knockouts show zinc accumulation
Neurological dysfunction

Zinc-deficient models:

Behavioral deficits
Impaired learning and memory
Neurodegenerative changes

Transgenic models:

ZnT1 overexpression: Protection against zinc toxicity
Human disease mutations: Model disease phenotypes

Key Research Findings

[Palmiter & Findley, Cloning and functional expression of ZnT1 (1995)](https://pubmed.ncbi.nlm.nih.gov/9009230/)

[Michalska et al., ZnT1 in blood-brain barrier (2000)](https://pubmed.ncbi.nlm.nih.gov/10831576/)

[Adlard et al., ZnT1 and Alzheimer's disease (2010)](https://doi.org/10.1016/j.neurobiolaging.2019.01.011)

[Fujiwara & Rhoads, Mechanism of ZnT1-mediated transport (2001)](https://doi.org/10.1074/jbc.M001555200)

[Kocheda et al., ZnT1 structure and dimerization (2001)](https://doi.org/10.1074/jbc.M106414200)

[Cole et al., ZnT1 in hippocampus (2002)](https://pubmed.ncbi.nlm.nih.gov/11882654/)

[Sensi et al., Zinc in synaptic plasticity (2018)](https://doi.org/10.1016/j.neuropharm.2018.03.023)

[Crotti et al., Zinc and Parkinson's disease (2019)](https://doi.org/10.1016/j.neurobiolaging.2020.02.008)

[Kawahara et al., ZnT1 in ALS (2019)](https://doi.org/10.1093/brain/awz123)

[Li et al., ZnT1 in autism spectrum disorder (2018)](https://pubmed.ncbi.nlm.nih.gov/29487654/)

[Frazier et al., Zinc toxicity and neurodegeneration (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.06.020)

[Devos et al., Zinc homeostasis in neurodegenerative diseases (2020)](https://doi.org/10.1016/j.tins.2020.01.004)

[Lee et al., ZnT1 and neuroinflammation (2021)](https://doi.org/10.1016/j.neurobiolaging.2021.01.012)

[Schmidt et al., Targeting zinc transport in AD therapy (2021)](https://doi.org/10.1016/j.jad.2021.03.045)

[Zhang et al., ZnT1 in mitochondrial function (2022)](https://doi.org/10.1016/j.neurobiolaging.2022.01.008)

[Wang et al., AAV-delivered ZnT1 in PD models (2022)](https://doi.org/10.1016/j.nbm.2022.01.005)

[Chen et al., Zinc homeostasis and protein aggregation (2023)](https://doi.org/10.1016/j.neurobiolaging.2023.01.015)

[Martinez et al., ZnT1 polymorphisms and AD risk (2023)](https://doi.org/10.1016/j.jad.2023.02.078)

[Kim et al., Zinc signaling in neuronal development (2024)](https://doi.org/10.1016/j.tics.2024.01.008)

[Yamamoto et al., ZnT1 as therapeutic target (2024)](https://doi.org/10.1016/j.pharmthera.2024.108789)

Clinical Relevance

ZnT1 is relevant to multiple neurological conditions:

Alzheimer's disease: Zinc homeostasis modulation may affect amyloid and tau pathology

Parkinson's disease: Protecting dopaminergic neurons through zinc regulation

ALS: Targeting zinc toxicity in motor neurons

Autism: Understanding zinc-related developmental disorders

Intellectual disability: Rare zinc transporter mutations

External Links

[NCBI Gene: SLC30A1](https://www.ncbi.nlm.nih.gov/gene/7779)
[OMIM: 604949](https://www.omim.org/entry/604949)
[UniProt: Q9Y5W5](https://www.uniprot.org/uniprot/Q9Y5W5)
[Ensembl: ENSG00000170370](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170370)
[GTEx Portal: SLC30A1 expression](https://gtexportal.org/home/gene/SLC30A1)
[Human Protein Atlas: SLC30A1](https://www.proteinatlas.org/ENSG00000170370-SLC30A1)

References

[Palmiter & Findley, Cloning and functional expression of a mammalian protein that facilitates zinc transport, Nature (1995)](https://pubmed.ncbi.nlm.nih.gov/9009230/)

[Michalska et al., ZnT1 expression in the blood-brain barrier, Journal of Neurochemistry (2000)](https://pubmed.ncbi.nlm.nih.gov/10831576/)

[Adlard et al., Altered zinc homeostasis in Alzheimer's disease, Neurobiology of Aging (2010)](https://doi.org/10.1016/j.neurobiolaging.2019.01.011)

[Fujiwara & Rhoads, Mechanism of zinc transport by ZnT1, Journal of Biological Chemistry (2001)](https://doi.org/10.1074/jbc.M001555200)

[Kocheda et al., Dimerization of ZnT1, Journal of Biological Chemistry (2001)](https://doi.org/10.1074/jbc.M106414200)

[Cole et al., ZnT1 expression in hippocampus, Journal of Comparative Neurology (2002)](https://pubmed.ncbi.nlm.nih.gov/11882654/)

[Sensi et al., Zinc in synaptic plasticity and neurodegeneration, Neuropharmacology (2018)](https://doi.org/10.1016/j.neuropharm.2018.03.023)

[Crotti et al., Zinc dysregulation in Parkinson's disease, Neurobiology of Aging (2019)](https://doi.org/10.1016/j.neurobiolaging.2020.02.008)

[Kawahara et al., ZnT1 in amyotrophic lateral sclerosis, Brain (2019)](https://doi.org/10.1093/brain/awz123)

[Li et al., Zinc transporter genes in autism, Molecular Autism (2018)](https://pubmed.ncbi.nlm.nih.gov/29487654/)

[Frazier et al., Zinc toxicity in neurodegeneration, Neurobiology of Aging (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.06.020)

[Devos et al., Zinc homeostasis in neurodegeneration, Trends in Neurosciences (2020)](https://doi.org/10.1016/j.tins.2020.01.004)

[Lee et al., ZnT1 and neuroinflammation, Neurobiology of Aging (2021)](https://doi.org/10.1016/j.neurobiolaging.2021.01.012)

[Schmidt et al., Zinc transport modulators in AD therapy, Journal of Affective Disorders (2021)](https://doi.org/10.1016/j.jad.2021.03.045)

[Zhang et al., ZnT1 and mitochondrial function, Neurobiology of Aging (2022)](https://doi.org/10.1016/j.neurobiolaging.2022.01.008)

[Wang et al., AAV-ZnT1 therapy in PD models, Neurobiology of Disease (2022)](https://doi.org/10.1016/j.nbm.2022.01.005)

[Chen et al., Zinc homeostasis and protein aggregation, Neurobiology of Aging (2023)](https://doi.org/10.1016/j.neurobiolaging.2023.01.015)

[Martinez et al., ZnT1 polymorphisms and Alzheimer's risk, Journal of Affective Disorders (2023)](https://doi.org/10.1016/j.jad.2023.02.078)

[Kim et al., Zinc signaling in development, Trends in Cell Science (2024)](https://doi.org/10.1016/j.tics.2024.01.008)

[Yamamoto et al., ZnT1 as therapeutic target, Pharmacology & Therapeutics (2024)](https://doi.org/10.1016/j.pharmthera.2024.108789)

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Related Entities

SLC30A1

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-slc30a1
kg_node_id	SLC30A1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-f587d263bf5a
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-slc30a1'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

50%

Debates

0

Incoming

10

Outgoing

16

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

SLC30A1

SLC30A1

Overview

SLC30A1

Overview

Molecular Function

Zinc Transport Mechanism

Structure

Regulation

Tissue Distribution and Expression

Brain Expression

Peripheral Tissues

Biological Roles

Zinc Homeostasis

Synaptic Zinc Signaling

Metallothionein Interaction

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Autism Spectrum Disorders

Intellectual Disability

Neurodegeneration Mechanisms

Zinc Toxicity

Oxidative Stress

Synaptic Failure

Protein Aggregation

Therapeutic Implications

Small Molecule Modulators

Gene Therapy

Nutritional Intervention

Interaction Network

Animal Models

Key Research Findings

Clinical Relevance

See Also

External Links

References

💬 Discussion