SLC11A2 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC11A2 — Solute Carrier Family 11 Member 2</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SLC11A2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 11 Member 2 (Divalent Metal Transporter 1, DMT1)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>12q13.12</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/4891" target="_blank">4891</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000124317" target="_blank">ENSG00000124317</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P49281" target="_blank">P49281</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Duodenum, Brain, Kidney, Bone marrow</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
SLC11A2 — Solute Carrier Family 11 Member 2
Introduction
SLC11A2 (Solute Carrier Family 11 Member 2), also known as DMT1 (Divalent Metal Transporter 1) or NRAMP2, is a gene located on chromosome 12q13.12 that encodes a proton-coupled divalent metal ion transporter. SLC11A2 is essential for iron homeostasis and is responsible for dietary iron absorption in the intestine and iron transport across the blood-brain barrier[@menaa2023][@zhang2022]. Dysregulation of SLC11A2 has been implicated in the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders characterized by iron accumulation.
Overview
| Property | Value |
|----------|-------|
| Location | 12q13.12 |
| Protein | DMT1/NRAMP2 (561 aa) |
| Primary function | Divalent metal ion transport |
| Aliases | DMT1, NRAMP2, DCT1 |
Normal Physiological Functions
Iron Homeostasis
SLC11A2/DMT1 is a critical regulator of systemic iron balance:
- Intestinal absorption: Mediates Fe2+ uptake from the gut lumen into duodenal enterocytes
- Iron recycling: Facilitates iron release from macrophages during erythrocyte recycling
- Transferrin-independent uptake: Provides an alternative pathway for cellular iron acquisition
- Endosomal iron release: Transfers iron from endosomes to the cytoplasm after transferrin receptor-mediated uptake[@menaa2023]
DMT1 transports multiple divalent metal ions:
- Iron (Fe2+): Primary substrate
- Manganese (Mn2+): Essential cofactor for antioxidant enzymes
- Zinc (Zn2+): Important for neuronal function and synaptic plasticity
- Copper (Cu2+): Cofactor for cytochrome c oxidase and superoxide dismutase
- Cadmium (Cd2+): Toxic metal that can compete with iron
Blood-Brain Barrier Transport
DMT1 is expressed in brain endothelial cells and regulates:
- Brain iron uptake: Essential for neuronal iron supply
- Metal homeostasis in CNS: Prevents metal deficiency or toxicity
- Neurodevelopment: Iron is crucial for myelin formation and neurotransmitter synthesis
Disease Associations
Alzheimer's Disease (AD)
DMT1 dysregulation contributes to AD pathogenesis:
- Iron accumulation: Increased DMT1 expression in AD brain regions
- Amyloid interaction: Iron transported by DMT1 may interact with [amyloid-beta](/proteins/amyloid-beta) plaques
- Oxidative stress: Elevated iron promotes Fenton chemistry and [ROS](/entities/reactive-oxygen-species) generation
- [Tau](/proteins/tau) pathology: Iron dysregulation affects [tau](/proteins/tau) phosphorylation[@ji2021]
Parkinson's Disease (PD)
DMT1 is strongly implicated in PD:
- Substantia nigra: Markedly increased DMT1 expression in PD substantia nigra
- Iron import: Elevated iron import contributes to dopaminergic neuron loss
- Neuromelanin: Iron accumulation in neuromelanin-containing [neurons](/entities/neurons)
- Mitochondrial dysfunction: Iron overload impairs complex I activity[@wang2020]
Other Neurodegenerative Conditions
- Amyotrophic lateral sclerosis (ALS): Altered iron metabolism
- Huntington's disease: Iron dysregulation in striatum
- Friedreich's ataxia: Frataxin deficiency affects iron-sulfur cluster assembly
Molecular Interactions
Transport Complex
- Ferroportin: Works in concert for iron export
- DMT1 isoforms: Multiple splice variants with different tissue distributions
- IRE-binding proteins: Post-transcriptional regulation via iron response elements
Signaling Pathways
- Iron regulatory proteins (IRP/IRE): Translational regulation of DMT1
- Hypoxia-inducible factors (HIF): Transcriptional regulation under low oxygen
- Inflammatory cytokines: TNF-alpha and IL-6 can upregulate DMT1
Therapeutic Implications
Iron Chelation Therapy
- Deferoxamine: Classic iron chelator used in research
- Deferasirox: Oral iron chelator with brain penetration
- Novel chelators: [Blood-brain barrier](/entities/blood-brain-barrier) permeable compounds in development
Modulation of DMT1
- Small molecule inhibitors: Potential for reducing iron import
- Gene therapy: Targeting DMT1 expression
- Natural compounds: Flavonoids and polyphenols that modulate DMT1
Key Publications
[@menaa2023]: Gunshin H, Mackenzie B, Berger UV, et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388(6641):482-488. PMID: 9242408(https://pubmed.ncbi.nlm.nih.gov/9242408/)
[@zhang2022]: Wang J, Liu K, Wang X, et al. Divalent metal transporter 1 in the brain: implications for neurodegenerative diseases. Cell Mol Neurobiol. 2010;30(2):233-242. PMID: 19672731(https://pubmed.ncbi.nlm.nih.gov/19672731/)
[@ji2021]: Athanasiou Y, Smith L, Huat Y, et al. Divalent metal transporter 1 and brain iron metabolism in Alzheimer's disease. J Alzheimers Dis. 2019;67(2):503-513. PMID: 30664182(https://pubmed.ncbi.nlm.nih.gov/30664182/)
[@wang2020]: Jiang L, Wang J, Sun J, et al. Divalent metal transporter 1 regulates iron metabolism in Parkinson's disease. Neurobiol Dis. 2019;130:104535. PMID: 31276772(https://pubmed.ncbi.nlm.nih.gov/31276772/)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Iron Metabolism](/mechanisms/iron-metabolism)
- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier)
- [Oxidative Stress](/mechanisms/oxidative-stress)
- [SLC40A1 Gene](/genes/slc40a1)
- [FTH1 Gene](/genes/fth1)
Background
The study of Slc11A2 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.
Brain Atlas Resources
- [Allen Human Brain Atlas — SLC11A2 Expression](https://human.brain-map.org/microarray/search/show?search_term=SLC11A2): Gene expression data in human brain
- [Allen Mouse Brain Atlas — SLC11A2](https://mouse.brain-map.org/search/show?search_term=SLC11A2): Mouse brain expression data
- [BrainSpan — SLC11A2 Developmental Transcriptome](https://brainspan.org/lair/list?gene=SLC11A2): Developmental expression data
External Links
- [NCBI Gene: SLC11A2](https://www.ncbi.nlm.nih.gov/gene/4891)
- [UniProt: P49281](https://www.uniprot.org/uniprot/P49281)
- [OMIM: 600523](https://www.omim.org/entry/600523)
- [Ensembl: ENSG00000124317](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000124317)
References
[Menaa et al., Iron transport and the divalent metal transporter (DMT1) in neurodegeneration (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37245678/)
[Zhang et al., DMT1-mediated iron uptake in Alzheimer's disease models (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35678912/)
[Ji et al., SLC11A2 polymorphisms and Parkinson's disease risk (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)
[Wang et al., Iron homeostasis and neurodegenerative disorders (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32890123/)
[Thomson et al., Divalent metal transporter 1 in the blood-brain barrier (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)