SLC30A6 — Solute Carrier Family 3 Member 0A6 (SLC30A6) <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosome </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Associated Diseases </td>Gene Symbol </td>Protein Name </td>Gene Family </td>Chromosomal Location </td>Gene ID (NCBI) </td>Protein Length </td>
...
SLC30A6 — Solute Carrier Family 3 Member 0A6 (SLC30A6) <table class="infobox infobox-gene">Symbol </td>Full Name </td>Chromosome </td>NCBI Gene ID </td>OMIM </td>Ensembl ID </td>UniProt ID </td>Associated Diseases </td>Gene Symbol </td>Protein Name </td>Gene Family </td>Chromosomal Location </td>Gene ID (NCBI) </td>Protein Length </td>UniProt ID </td>Tissue Specificity </td>
{{.infobox .infobox-gene}}
Overview SLC30A6 (Solute Carrier Family 30 Member 6), also known as ZnT6 (Zinc Transporter 6), is a zinc efflux transporter belonging to the CDF (Cation Diffusion Facilitator) family.[@palmiter2004] This protein plays a crucial role in cellular zinc homeostasis by pumping zinc from the cytoplasm into intracellular vesicles or the extracellular space.
The ZnT family consists of 10 members (ZnT1-10), each with distinct tissue expression patterns and subcellular localizations. ZnT6 is primarily expressed in the brain and is localized to the Golgi apparatus and secretory vesicles, where it sequesters zinc into these compartments.[@kambe2015] This localization is particularly relevant for [neurons](/entities/neurons), where vesicular zinc serves important signaling functions.
Protein Structure and Function
Structure ZnT6 contains six transmembrane domains with the N- and C-termini facing the cytoplasm. Like other ZnT proteins, it features a histidine-rich loop between transmembrane domains IV and V, which is thought to be involved in zinc binding and transport.
Mechanism of Action ZnT6 functions as a zinc efflux pump:
Uses the proton gradient as an energy source
Transports zinc from the cytoplasm into vesicles
Important for zinc sequestration in specialized cells
Works in concert with ZIP importers to maintain zinc homeostasis
Subcellular Localization ZnT6 is primarily localized to:
Golgi apparatus : Stores zinc in the Golgi lumenSecretory vesicles : Packages zinc into secretory granulesEndoplasmic reticulum : May contribute to ER zinc homeostasisRole in Neurodegeneration
Alzheimer's Disease[@adlard2014] ZnT6 has been implicated in Alzheimer's disease pathophysiology:
Zinc homeostasis : Disrupted in AD brainsAmyloid processing : Zinc affects [amyloid precursor protein](/entities/app-protein) (APP) processingSynaptic function : Altered vesicular zinc signalingOxidative stress : ZnT6 deficiency may increase oxidative damageParkinson's Disease
Substantia nigra : Altered ZnT6 expression in PD brain[Alpha-synuclein](/proteins/alpha-synuclein) : Zinc influences protein aggregationMitochondrial function : Cellular zinc affects mitochondrial healthNeuroinflammation : Zinc modulation of glial cell functionOther Neurodegenerative Conditions
Huntington's disease : Zinc dysregulation in HD modelsAmyotrophic lateral sclerosis : Altered zinc homeostasis in motor neuronsPrion diseases : Zinc metabolism affected in prion disordersTherapeutic Implications
Targeting ZnT6
Drug Development
Small molecule modulators : Develop selective ZnT6-targeting compoundsGene therapy : Modulate SLC30A6 expressionCombination therapies : Target multiple zinc transporters
Research Findings
Expression Studies
ZnT6 is highly expressed in hippocampal neurons
Upregulated in response to zinc supplementation
Decreased expression in aging brain
Animal Models
ZnT6 knockout mice show altered zinc homeostasis
Phenotypes include behavioral changes
Synaptic function deficits observed
Clinical Significance While no direct disease-causing mutations in SLC30A6 have been identified, polymorphisms and expression alterations are associated with:
Neurodegenerative disease risk
Cognitive function
Response to zinc supplementation
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Zinc](/genes/gatad2a)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
External Links
[NCBI Gene: 28517](https://www.ncbi.nlm.nih.gov/gene/28517)
[Ensembl: ENSG00000138401](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138401)
[UniProt: Q6NXR1](https://www.uniprot.org/uniprot/Q6NXR1)
References
[Unknown, Palmiter & Huang, ZnT transporters (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15525652/)
[Kambe et al., ZnT family (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25900241/)
[Adlard et al., Zinc in Alzheimer's disease (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/24365726/)
[Sensi et al., Zinc homeostasis in neurodegeneration (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19373613/)
[Frazzini et al., ZnT6 and neurodegeneration (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29562276/) Show full description