SLC7A11 (xCT): Cystine/Glutamate Antiporter in Ferroptosis and Cancer
A comprehensive biomedical overview of SLC7A11, its genomic context, expression, disease associations, mutations, and functional roles.
Gene Information Card
| Symbol | SLC7A11 |
|---|---|
| Full Name | Solute carrier family 7 member 11 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q28.3 |
| NCBI Gene ID | 23657 ncbi.nlm.nih.gov/gene/23657 |
| Ensembl ID | ENSG00000151012 |
| UniProt ID | Q9UPY5 |
| OMIM ID | 607933 |
| HGNC ID | HGNC:11059 |
| Aliases | xCT, CCBR1, FLJ10316 |
Description
SLC7A11 encodes the cystine/glutamate antiporter xCT, a sodium-independent transporter that mediates the exchange of extracellular cystine for intracellular glutamate. This transporter is critical for maintaining intracellular cysteine levels, which are rate-limiting for glutathione synthesis and redox homeostasis. SLC7A11 is a key regulator of ferroptosis, a form of iron-dependent cell death, and is frequently upregulated in various cancers to support antioxidant defense and proliferation. Its expression is also implicated in neurological disorders and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of SLC7A11 enhances cystine uptake, promoting glutathione synthesis and suppressing ferroptosis, thereby supporting tumor growth and therapy resistance. | High expression observed in lung, breast, liver, and pancreatic cancers; associated with poor prognosis (COSMIC, literature). |
| Ferroptosis-related pathologies (e.g., ischemia-reperfusion injury, neurodegeneration) | Dysregulation of SLC7A11 can lead to altered cystine transport, affecting glutathione levels and lipid peroxidation, influencing ferroptosis susceptibility. | Experimental models; ClinVar lists variants with uncertain significance. |
| Glutamate excitotoxicity (neurological) | Increased SLC7A11 activity can elevate extracellular glutamate, contributing to excitotoxic neuronal damage. | In vitro and animal studies; OMIM notes relevance to neurological phenotypes. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in specific regions (e.g., hippocampus, cortex) |
| Liver | Moderate | Moderate expression in hepatocytes |
| Kidney | Moderate | Expression in renal tubules |
| Lung | Low | Low baseline expression, inducible under stress |
| Pancreas | Low | Low expression in normal pancreatic tissue |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High | Commonly used model for SLC7A11 studies |
| A549 (lung cancer) | High | High expression associated with oxidative stress resistance |
| MCF7 (breast cancer) | Moderate | Expression varies with estrogen receptor status |
| HepG2 (liver cancer) | Moderate | Expression inducible by oxidative stress |
| U87 (glioblastoma) | High | High expression linked to glutamate release and tumor invasion |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.739G>A (p.Val247Met) | Missense | Rare (0.01% in gnomAD) | Uncertain significance; may affect transporter activity |
| c.1243C>T (p.Arg415Cys) | Missense | Rare | Potential impact on protein stability; ClinVar lists as VUS |
| c.157C>T (p.Arg53Trp) | Missense | Not reported in large cohorts | Predicted deleterious; functional studies lacking |
| Copy number gain | CNV | Frequent in cancers (e.g., lung, breast) | Amplification leads to overexpression and ferroptosis resistance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations are rare and may impair cystine transport, leading to reduced glutathione synthesis and increased ferroptosis susceptibility. No germline pathogenic variants are well-documented in ClinVar.
Gain of Function (GOF)
Gain-of-function is primarily achieved through gene amplification or transcriptional upregulation, enhancing cystine uptake and ferroptosis resistance in tumors.
Dominant Negative (DN)
No evidence for dominant-negative effects; SLC7A11 functions as a dimer, but no such mutations have been reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cystine/glutamate transport (Reactome: R-HSA-428643)
• Glutathione synthesis and redox homeostasis (KEGG: hsa00480)
• Ferroptosis (KEGG: hsa04216)
Protein Summary
The SLC7A11 protein (xCT) is a 501-amino acid transmembrane protein with 12 predicted transmembrane domains. It forms a heterodimer with SLC3A2 (CD98 heavy chain) to function as a cystine/glutamate antiporter. The protein is localized to the plasma membrane and is regulated by oxidative stress, oncogenic signaling (e.g., NRF2, ATF4), and post-translational modifications. Its primary role is to import cystine, which is reduced to cysteine for glutathione synthesis, thereby protecting cells from oxidative damage and ferroptosis. In cancer, SLC7A11 overexpression is a key mechanism of therapy resistance, making it a promising therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC7A11 Knockout HEK293 Cell Line | EDJ-KQ17899 | Human | 23657 | Details Get a Quote |
| SLC7A11 Knockout HeLa Cell Line | EDJ-KQ18180 | Human | 23657 | Details Get a Quote |
| SLC7A11 Knockout HCT 116 Cell Line | EDJ-KQ18896 | Human | 23657 | Details Get a Quote |
| SLC7A11 Knockout A-549 Cell Line | EDJ-KQ20237 | Human | 23657 | Details Get a Quote |
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