SLC7A11 Gene - xCT Cystine/Glutamate Antiporter

SLC7A11 Gene - xCT Cystine/Glutamate Antiporter

Introduction

Pathway Diagram

```mermaid
flowchart TD
SLC7A11["SLC7A11<br/>Gene"]
xCT["xCT Protein<br/>(Cystine/Glutamate<br/>Antiporter)"]
system_xc["System xc-<br/>Transport System"]
cystine["Cystine<br/>Import"]
glutamate["Glutamate<br/>Export"]
GSH["Glutathione<br/>Synthesis"]
GPX4["GPX4<br/>Enzyme"]
ROS["Reactive Oxygen<br/>Species"]
ferroptosis["Ferroptosis<br/>Cell Death"]

Nrf2["Nrf2<br/>Transcription Factor"]
FOXK2["FOXK2<br/>Transcription Factor"]

ALS["Amyotrophic<br/>Lateral Sclerosis"]
MS["Multiple<br/>Sclerosis"]
neuroinflam["Neuroinflammation"]
neuroprot["Neuroprotection"]

SLC7A11 -->|"encodes"| xCT
xCT -->|"forms"| system_xc
system_xc -->|"imports"| cystine
system_xc -->|"exports"| glutamate
cystine -->|"enables"| GSH
GSH -->|"activates"| GPX4
GPX4 -->|"inhibits"| ferroptosis
SLC7A11 -->|"inhibits"| ROS
ROS -->|"promotes"| ferroptosis

Nrf2 -->|"upregulates"| SLC7A11
FOXK2 -->|"regulates"| SLC7A11

SLC7A11 -->|"therapeutic_target"| ALS
SLC7A11 -->|"therapeutic_target"| MS
ferroptosis -->|"contributes_to"| ALS
SLC7A11 -->|"inhibits"| neuroinflam
SLC7A11 -->|"promotes"| neuroprot

style SLC7A11 fill:#006494
style xCT fill:#006494
style system_xc fill:#006494
style GPX4 fill:#1b5e20
style GSH fill:#1b5e20
style neuroprot fill:#1b5e20
style Nrf2 fill:#4a1a6b
style FOXK2 fill:#4a1a6b
style ferroptosis fill:#ef5350
style

SLC7A11 Gene - xCT Cystine/Glutamate Antiporter

Introduction

Pathway Diagram

Slc7A11 Gene Xct Cystine Glutamate Antiporter is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@sato1999]
<table> [@lewerenz2013]
<tr><th colspan="2" style="background:#f0f0f0;">SLC7A11 (xCT)</th></tr> [@garciabermudez2020]
<tr><td><b>Gene Symbol</b></td><td>SLC7A11</td></tr> [@bridges2012]
<tr><td><b>Full Name</b></td><td>Solute Carrier Family 7 Member 11 (xCT)</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>4q28.3</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[23657](https://www.ncbi.nlm.nih.gov/gene/23657)</td></tr>
<tr><td><b>OMIM</b></td><td>[604719](https://www.omim.org/entry/604719)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000155511</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9UPN3](https://www.uniprot.org/uniprot/Q9UPN3)</td></tr>
<tr><td><b>Protein</b></td><td>xCT (SLC7A11)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease, Alzheimer's Disease, Cancer</td></tr>
</table>
</div>

Overview

SLC7A11 (xCT) encodes the light chain of the cystine/glutamate antiporter system Xc− (system x_c^−). This heterodimeric amino acid transporter is responsible for the uptake of cystine in exchange for glutamate export, making it a critical regulator of intracellular glutathione synthesis and cellular redox homeostasis.

Molecular Function

System Xc− Activity

The SLC7A11 protein forms the functional light chain of system Xc−, a sodium-independent cystine/glutamate antiporter:

• Substrate Specificity: Imports cystine (oxidized dimer of cysteine) in exchange for exporting glutamate
• Stoichiometry: 1:1 exchange of cystine for glutamate
• Driving Force: The inward gradient of cystine and outward gradient of glutamate drive transport
• Antiporter Mechanism: Obligatory exchange - both substrates must be transported simultaneously

Role in Glutathione Synthesis

The primary function of SLC7A11 is to provide cysteine for glutathione (GSH) synthesis:

Expression Pattern

Brain Expression

SLC7A11 is expressed in various brain cell types:

• [Astrocytes](/entities/astrocytes): High expression in astrocytic glia, supporting neuronal antioxidant defense
• [Microglia](/entities/microglia): Moderate expression in immune cells of the brain
• [Neurons](/entities/neurons): Lower baseline expression, upregulated under oxidative stress
• Oligodendrocytes: Important for myelin maintenance given high lipid content

Regional Distribution

• [Cortex](/brain-regions/cortex): Moderate expression in cortical astrocytes
• Basal Ganglia: Higher expression in regions with dopaminergic neurons
• Spinal Cord: High expression in motor neurons (relevant to ALS)
• [Hippocampus](/brain-regions/hippocampus): Expression in pyramidal neurons and interneurons

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

• SLC7A11 dysfunction may contribute to motor neuron vulnerability
• Reduced cystine uptake leads to GSH depletion
• [Ferroptosis](/entities/ferroptosis) is implicated as a cell death mechanism in ALS
• System x_c^− modulators are being explored as therapeutic targets

Parkinson's Disease

• Dopaminergic neurons are particularly vulnerable to oxidative stress
• GSH depletion is observed in PD substantia nigra
• SLC7A11 activity may influence neuronal survival
• Cystine supplementation has shown neuroprotective effects in models

Alzheimer's Disease

• [Aβ](/proteins/amyloid-beta) induces oxidative stress in neurons and astrocytes
• Astrocytic xCT function may be impaired in AD
• Therapeutic strategies aim to boost GSH via system x_c^−

Cancer (Paradoxical Role)

• Many cancers upregulate SLC7A11 to survive oxidative stress
• xCT inhibitors (sulfasalazine, erastin) are being developed as anticancer agents

Therapeutic Targeting

xCT Inhibitors

| Drug/Compound | Mechanism | Stage | Notes |
|--------------|-----------|-------|-------|
| Sulfasalazine | Direct xCT inhibitor | Preclinical | FDA-approved for ulcerative colitis |
| Erastin | Ferroptosis inducer | Research | Directly inhibits system x_c^− |
| Sorafenib | Multikinase inhibitor includes xCT | Approved (cancer) | FDA-approved for various cancers |
| SAS | xCT blocker | Research | Used in combination therapies |

xCT Activators/NRF2 Modulators

• N-acetylcysteine (NAC): Cysteine prodrug, bypasses xCT
• Vitamin B6: Cofactor for cysteine metabolism
• NRF2 activators: Boost SLC7A11 expression indirectly

Research Directions

• Develop brain-penetrant xCT modulators
• Understand cell-type specific regulation of SLC7A11
• Explore gene therapy approaches to enhance xCT function
• Investigate combination therapies with antioxidants

Key Publications

See Also

• [Ferroptosis Pathway](/mechanisms/ferroptosis-pathway)
• [GPX4 Gene](/proteins/gpx4-protein)
• [Glutathione Metabolism](/mechanisms/oxidative-stress-pathway)
• [Oxidative Stress in Neurodegeneration](/mechanisms/oxidative-stress-pathway)
• [ALS Gene List](/diseases/als)
• [Parkinson's Disease Genes](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: SLC7A11](https://www.ncbi.nlm.nih.gov/gene/23657)
• [UniProt: Q9UPN3](https://www.uniprot.org/uniprot/Q9UPN3)
• [Ensembl: ENSG00000155511](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000155511)
• [GeneCards: SLC7A11](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC7A11)

Background

The study of Slc7A11 Gene Xct Cystine Glutamate Antiporter 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.

See Also

• SLC7A11 Protein
• xCT
• System xc-
• Ferroptosis Pathway
• Cystine/Glutamate Antiporter
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• Cancer

External Links

• [SLC7A11 - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/2810)
• [SLC7A11/xCT - UniProt](https://www.uniprot.org/uniprot/Q9UP50)

References

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Senescence-Induced Lipid Peroxidation Spreading](/hypothesis/h-7957bb2a) — <span style="color:#ffd54f;font-weight:600">0.54</span> · Target: GPX4/SLC7A11

Pathway Diagram

The following diagram shows the key molecular relationships involving SLC7A11 Gene - xCT Cystine/Glutamate Antiporter discovered through SciDEX knowledge graph analysis: