SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

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gene865 wordssynced 2026-04-02

SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SLC31A1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 31 Member 1 (Copper Transporter 1)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>9q32</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[10551](https://www.ncbi.nlm.nih.gov/gene/10551)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[603085](https://www.omim.org/entry/603085)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000137767</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[O15431](https://www.uniprot.org/uniprot/O15431)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Menkes disease (potential modifier), Wilson disease, Amyotrophic lateral sclerosis</td>
</tr>
</table>

Overview

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SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

Overview

Mermaid diagram (expand to render)

The SLC31A1 gene encodes Copper Transporter 1 (CTR1), a high-affinity plasma membrane copper uptake protein essential for cellular copper homeostasis [@ctr]. CTR1 is the primary gateway for copper acquisition in most cell types, mediating the rapid uptake of copper required for the function of copper-dependent enzymes throughout the body [@copper].

Copper is an essential trace element required for the activity of numerous enzymes critical to energy metabolism, antioxidant defense, neurotransmitter synthesis, and iron metabolism. However, excess copper is highly toxic, making the tight regulation provided by CTR1 and other copper transporters crucial for cellular health [@coppera].

Function and Mechanism

Copper Uptake

CTR1 functions as a high-affinity copper transporter, facilitating the import of Cu⁺ ions (the reduced form of copper) across the plasma membrane. The transporter operates as a trimer, forming a pore that conducts copper ions driven by the transmembrane copper gradient [@structure].

Key features of CTR1-mediated copper uptake:

High affinity: Kd in the low micromolar to nanomolar range
Rapid kinetics: Enables efficient copper acquisition even at low extracellular concentrations
Regulated expression: CTR1 levels are adjusted based on cellular copper status
Endocytosis: Copper uptake triggers CTR1 internalization and degradation [@regulation]

Interaction with Copper Chaperones

Once inside the cell, copper is immediately handed off to copper chaperones that direct it to specific destinations:

CCS (Copper Chaperone for SOD): Delivers copper to Cu/Zn superoxide dismutase (SOD1)
COX17: Delivers copper to cytochrome c oxidase in mitochondria
ATOX1: Delivers copper to copper-transporting ATPases (ATP7A, ATP7B) [@copperb]

This rapid chelation prevents free copper from participating in harmful redox reactions.

Expression Pattern

CTR1 is expressed in virtually all tissues, with particularly high expression in:

Intestine: Primary site of dietary copper absorption
Liver: Central organ for copper metabolism
Brain: [Neurons](/entities/neurons) and endothelial cells of the [blood-brain barrier](/entities/blood-brain-barrier)
Kidney: Involved in copper reabsorption
Heart and muscle: High metabolic demand tissues [@ctra]

In the brain, CTR1 is expressed in neurons, [astrocytes](/entities/astrocytes), and the blood-brain barrier, where it regulates copper entry into the central nervous system [@ctrb].

Role in Neurodegeneration

Copper in Alzheimer's Disease

Copper dysregulation is strongly implicated in Alzheimer's disease pathogenesis:

[Amyloid-beta](/proteins/amyloid-beta) interaction: Copper binds to amyloid-beta peptides, promoting aggregation and neurotoxicity [@copperc]
Oxidative stress: Copper-catalyzed Fenton reactions generate [reactive oxygen species](/entities/reactive-oxygen-species) (ROS)
Metal homeostasis disruption: Alzheimer's disease brains show altered copper levels
CTR1 expression changes: CTR1 expression is modified in Alzheimer's disease brains [@copperd]

Copper in Parkinson's Disease

Copper also plays a role in Parkinson's disease:

Alpha-synuclein interaction: Copper binds to alpha-synuclein, accelerating its aggregation [@coppere]
Mitochondrial function: Copper is required for proper mitochondrial electron transport
Dopaminergic neuron vulnerability: Copper metabolism affects dopamine neuron survival [@copperf]

Amyotrophic Lateral Sclerosis (ALS)

CTR1 may be relevant to ALS pathogenesis:

Copper metabolism is altered in ALS
CTR1 expression affects mutant SOD1 toxicity in familial ALS models
Copper chelation strategies have been explored as potential therapies [@copperg]

Disease Associations

Menkes Disease

While Menkes disease is primarily caused by mutations in ATP7A (a copper-transporting ATPase), CTR1 function can modify disease severity. Reduced CTR1 expression can exacerbate copper deficiency in Menkes disease [@ctrc].

Wilson Disease

Wilson disease, caused by ATP7B mutations, involves copper overload. CTR1 expression may influence the rate of copper accumulation and disease progression [@ctrd].

Cancer

CTR1 is frequently upregulated in cancers, where copper is needed for proliferation and angiogenesis. CTR1 expression correlates with tumor growth and metastatic potential [@ctre].

Therapeutic Implications

CTR1 is a potential therapeutic target:

Copper chelation therapy: For conditions of copper overload
Copper supplementation: For conditions of copper deficiency
Drug delivery: CTR1 can be exploited for targeted delivery of copper-based chemotherapeutic agents [@targeting]

References

Unknown, NCBI Gene: SLC31A1 (n.d.)

[Unknown, CTR1: a high-affinity copper transporter (PMID:9729270) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/9729270/)

[Unknown, Copper homeostasis in mammals (PMID:10806596) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/10806596/)

[Unknown, Copper toxicity and cellular defense (PMID:10699752) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/10699752/)

[Unknown, Structure and mechanism of CTR1 copper transporter (n.d.)](https://pubmed.ncbi.nlm.nih.gov/21988833/)

[Unknown, Regulation of CTR1 expression and function (n.d.)](https://pubmed.ncbi.nlm.nih.gov/12475939/)

[Unknown, Copper chaperones and intracellular trafficking (PMID:11099404) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/11099404/)

[Unknown, CTR1 tissue expression pattern (n.d.)](https://pubmed.ncbi.nlm.nih.gov/10831591/)

[Unknown, CTR1 in the blood-brain barrier (n.d.)](https://pubmed.ncbi.nlm.nih.gov/14596612/)

[Unknown, Copper and amyloid-beta interaction (PMID:15274604) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/15274604/)

[Unknown, Copper dysregulation in Alzheimer's disease (PMID:16877385) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/16877385/)

[Unknown, Copper and alpha-synuclein aggregation (PMID:16179542) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/16179542/)

[Unknown, Copper in Parkinson's disease (PMID:18682209) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/18682209/)

[Unknown, Copper metabolism in ALS (PMID:18624665) (n.d.)](https://pubmed.ncbi.nlm.nih.gov/18624665/)

[Unknown, CTR1 and Menkes disease modifier (n.d.)](https://pubmed.ncbi.nlm.nih.gov/11929852/)

[Unknown, CTR1 and Wilson disease progression (n.d.)](https://pubmed.ncbi.nlm.nih.gov/11739394/)

[Unknown, CTR1 in cancer biology (n.d.)](https://pubmed.ncbi.nlm.nih.gov/15894610/)

[Unknown, Targeting CTR1 for drug delivery (n.d.)](https://pubmed.ncbi.nlm.nih.gov/20345751/)

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SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

Overview

SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

Overview

Function and Mechanism

Copper Uptake

Interaction with Copper Chaperones

Expression Pattern

Role in Neurodegeneration

Copper in Alzheimer's Disease

Copper in Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Disease Associations

Menkes Disease

Wilson Disease

Cancer

Therapeutic Implications

See Also

References