SLC7A11

Summary

SLC7A11 (solute carrier family 7 member 11, HGNC:11059) is a protein-coding gene on chromosome 4q28.3, encoding Cystine/glutamate transporter (Q9UPY5). Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane.

This gene encodes a member of a heteromeric, sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate. In this system, designated Xc(-), the anionic form of cysteine is transported in exchange for glutamate. This protein has been identified as the predominant mediator of Kaposi sarcoma-associated herpesvirus fusion and entry permissiveness into cells. Also, increased expression of this gene in primary gliomas (compared to normal brain tissue) was associated with increased glutamate secretion via the XCT channels, resulting in neuronal cell death.

Source: NCBI Gene 23657 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 78 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11059
Approved symbol	SLC7A11
Name	solute carrier family 7 member 11
Location	4q28.3
Locus type	gene with protein product
Status	Approved
Aliases	xCT
Ensembl gene	ENSG00000151012
Ensembl biotype	protein_coding
OMIM	607933
Entrez	23657

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000280612, ENST00000509248

RefSeq mRNA: 1 — MANE Select: NM_014331 NM_014331

CCDS: CCDS3742

Canonical transcript exons

ENST00000280612 — 12 exons

Exon	Start	End
ENSE00000997220	138236325	138236451
ENSE00001171350	138182297	138182393
ENSE00001171368	138185121	138185244
ENSE00001171375	138214585	138214629
ENSE00001171386	138219266	138219365
ENSE00001171399	138223199	138223324
ENSE00001171409	138232267	138232382
ENSE00001251686	138241793	138242349
ENSE00001313399	138164097	138172017
ENSE00003490524	138180641	138180790
ENSE00003565876	138183202	138183305
ENSE00003632183	138179217	138179394

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 94.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.8368 / max 2392.8602, expressed in 1661 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54007	41.2428	1600
54008	3.0005	973
54009	2.9923	997
54004	1.4920	582
54005	1.0134	535
54006	0.7883	381
203343	0.3695	191
54002	0.2287	81
203346	0.1751	72
203347	0.1355	67

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cranial nerve II	UBERON:0000941	94.78	gold quality
stromal cell of endometrium	CL:0002255	94.52	gold quality
lateral globus pallidus	UBERON:0002476	94.02	gold quality
medial globus pallidus	UBERON:0002477	93.35	gold quality
globus pallidus	UBERON:0001875	92.73	gold quality
entorhinal cortex	UBERON:0002728	90.73	gold quality
cartilage tissue	UBERON:0002418	90.51	gold quality
endothelial cell	CL:0000115	90.50	gold quality
medulla oblongata	UBERON:0001896	90.44	gold quality
gingival epithelium	UBERON:0001949	90.31	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.24	gold quality
superior vestibular nucleus	UBERON:0007227	90.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.58	gold quality
ventral tegmental area	UBERON:0002691	89.52	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.35	gold quality
middle temporal gyrus	UBERON:0002771	89.22	gold quality
substantia nigra pars compacta	UBERON:0001965	89.21	gold quality
tongue squamous epithelium	UBERON:0006919	89.16	gold quality
islet of Langerhans	UBERON:0000006	89.06	gold quality
gingiva	UBERON:0001828	88.55	gold quality
corpus epididymis	UBERON:0004359	88.47	gold quality
subthalamic nucleus	UBERON:0001906	88.37	gold quality
inferior olivary complex	UBERON:0002127	88.34	gold quality
choroid plexus epithelium	UBERON:0003911	88.31	gold quality
trigeminal ganglion	UBERON:0001675	87.93	gold quality
corpus callosum	UBERON:0002336	87.61	gold quality
superior frontal gyrus	UBERON:0002661	86.10	gold quality
postcentral gyrus	UBERON:0002581	85.97	gold quality
parietal lobe	UBERON:0001872	85.70	gold quality
temporal lobe	UBERON:0001871	85.67	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2853.02
E-HCAD-29	yes	2245.53
E-HCAD-35	yes	1301.49
E-GEOD-75688	yes	1273.65
E-CURD-7	yes	1126.50
E-ENAD-21	yes	1126.50
E-MTAB-8142	yes	84.13
E-GEOD-81383	no	832.56
E-CURD-11	no	610.62
E-MTAB-10290	no	268.65
E-MTAB-7008	no	110.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF4, JUN, NFE2, NFE2L2, NRF1, POU2F1, TCF7L2

miRNA regulators (miRDB)

412 targeting SLC7A11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126

Literature-anchored findings (GeneRIF, showing 40)

• Cys(327) is a functionally important residue accessible to the aqueous extracellular environment and is structurally linked to the permeation pathway and/or the substrate binding site (PMID:14722095)
• topological model for xCT of 12 transmembrane domains with the N and C termini located inside the cell (PMID:15151999)
• Expression of Tat led to decrease in glutathione and increase in gamma-glutamyl transpeptidase. The transport function of xc-was upregulated and was accompanied by increases in mRNAs for xCT and 4F2hc and in corresponding protein levels. (PMID:15326101)
• xCT was identified as the receptor mediating KSHV cell fusion; KSHV target cell permissiveness correlated closely with endogenous expression of xCT messenger RNA and protein in diverse cell types (PMID:16574866)
• These results suggest that reduced calcium signaling impairs AP-1 activation and that xCT expression may directly affect cell proliferation. (PMID:18054200)
• Induction of xCT led to glutamate-inhibitable cystine uptake and an increased rate of cysteine release from cells; overexpression of xCT in smooth muscle cells or endothelial cells led to glutamate-inhibitable cysteine release. (PMID:18287333)
• Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema. (PMID:18469825)
• The results suggest that the x(c)(-) transporter by enhancing glutathione biosynthesis plays a major role in pancreatic cancer growth, therapy resistance and represents a potential therapeutic target for the disease. (PMID:18648370)
• Caveolin-1 was upregulated and beta-catenin was recruited to the plasma membrane when xCT was deficient, which were followed by the inhibition of beta-catenin transcriptional activity. (PMID:19015640)
• long term activation of the phospho-eIF2alpha/ATF4/xCT signaling module by the specific eIF2alpha phosphatase inhibitor, salubrinal, induces resistance against oxidative glutamate toxicity in the hippocampal cell line HT22 and primary cortical neurons (PMID:19017641)
• Expression of xCT is significantly reduced in low-grade oligodendroglial tumours harbouring LOH1p (PMID:19207949)
• x(c)(-) transporter provides a useful target for glioma therapy. (PMID:20007406)
• Review discusses system xc- function in vitro and in vivo, its role as an ambivalent drug target, and the relevance of oxytosis mediated by inhibition of xCT for identification of neuroprotective proteins and signaling pathways. (PMID:20053169)
• The cystine/glutamate antiporter demonstrates its major role of cystine and glutamate transport while modulating intracellular glutathione content and efflux in dendritic cells during cell differentiation and cross-presentation in a transgenic system. (PMID:20733204)
• The pathways modify system activity beyond the level of xCT transcription, including regulation on the level of membrane trafficking and substrate availability, especially the regulation by glutamate transport through excitatory amino acid transporters. (PMID:21369940)
• Data show that SLC7A11 is the direct target of miR-26b and its expression is remarkably increased in both breast cancer cell lines and clinical samples. (PMID:21510944)
• SLC7A11 is a functional target gene of the BACH1 transcription factor according to ChIP-seq and knockdown analysis in HEK 293 cells. (PMID:21555518)
• Results reveal that increased expression of the cystine/glutamate antiporter system xCT in multiple sclerosis provides a link between inflammation and excitotoxicity in demyelinating diseases. (PMID:21639880)
• Both IGF-1 and TGF-beta stimulated system xc-mediated cystine uptake in dental pulp cells. (PMID:21689549)
• These findings suggest that xCT is an independent predictive factor in glioblastomas (PMID:23096413)
• These observations suggest that the expression of xCT in esophageal squamous cell carcinoma (ESCC) cells might affect the G1/S checkpoint and impact on the prognosis of ESCC patients (PMID:23771433)
• the xCT antiporter, which is expressed on one-third of triple-negative breast tumors in this study, may have a role in glutamine updake and dependence (PMID:24094812)
• Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy (PMID:24516043)
• IGF-I regulates cystine uptake and cellular redox status by activating the expression and function of xCT in estrogen receptor-positive (ER(+)) breast cancer cells by a mechanism that relies on the IGF receptor substrate-1 (IRS-1). (PMID:24686172)
• Results show that Nrf2 and ATF4 were upregulated by proteasome inhibition and cooperatively enhance human xCT gene expression upon proteasome inhibition. (PMID:25002527)
• Data indicate that cystine-glutamate exchange transporter protein SLC7A11 mRNA is regulated by cellular stress and nonsense-mediated RNA decay (NMD). (PMID:25399695)
• We discovered that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT. (PMID:25860939)
• increased SLC7A11 expression predicted shorter malignant glioma patient survival. (PMID:26019222)
• the rate of cystine uptake was significantly faster than the rate of glutamate release in human glioma cells. (PMID:26252954)
• Sulfasalazine, a relatively non-toxic drug that targets cystine transporter, may, in combination with CDDP, be an effective therapy for colorectal cancer. (PMID:26254540)
• Study demonstrated that the mRNA expression levels of the two system xc- subunits, SLC7A11 and SLC3A2, in peripheral white blood cells are lowered in patients with schizophrenia than healthy individuals (PMID:26540405)
• Although LCN2 increased intracellular iron concentrations, LCN2-induced GSH may catalyze and override oxidative stress via CD44 and xCT, and subsequently enhance the survival of clear cell carcinoma tumor cells in oxidative stress-rich environment. (PMID:26729415)
• The most frequent SLC7A7 mutation in Japanese LPI patients is p.R410*, which is a founder effect mutation in northern Japan. (PMID:26865117)
• MUC1-C binds directly with CD44v and in turn promotes stability of xCT in the cell membrane (PMID:26930718)
• High SLC7A11 expression is associated with glioma. (PMID:26980765)
• Authors found that the xCT expression was increased in peripheral blood monocyte of active tuberculosis. xCT expression in macrophage was induced by Mycobacterium tuberculosis (Mtb) through TLR2/Akt- and p38-dependent signaling pathway. (PMID:27129162)
• Mechanistically, CD44v interacts with and stabilizes xCT and thereby promotes the uptake of cysteine for glutathione synthesis and stimulates side-population cell enrichment. (PMID:27279909)
• Results suggest that expression of SLC7A11 in the context of glioma contributes to tumorigenesis, tumor progression, and resistance to standard chemotherapy. (PMID:27658422)
• simultaneous mutations at all four acetylation sites completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Moreover, p53(4KR) is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated (PMID:27705786)
• Genetic and pharmacological inhibition of xCT potentiated the cytotoxic effects of aspirin plus sorafenib; this effect was diminished by xCT overexpression. Low-dose aspirin plus sorafenib enhanced the cytotoxicity of cisplatin in resistant HNC cells through xCT inhibition and oxidant and DNA damage. (PMID:28057599)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a2	ENSDARG00000037097
danio_rerio	slc7a11	ENSDARG00000071384
mus_musculus	Slc7a11	ENSMUSG00000027737
rattus_norvegicus	Slc7a11	ENSRNOG00000010210
drosophila_melanogaster	mnd	FBGN0002778
drosophila_melanogaster	CG7255	FBGN0036493
drosophila_melanogaster	CG5535	FBGN0036764
drosophila_melanogaster	slif	FBGN0037203
drosophila_melanogaster	CG1607	FBGN0039844
caenorhabditis_elegans		WBGENE00000002
caenorhabditis_elegans		WBGENE00000003
caenorhabditis_elegans		WBGENE00000005
caenorhabditis_elegans	aat-9	WBGENE00000010
caenorhabditis_elegans		WBGENE00015197
caenorhabditis_elegans		WBGENE00017747

Paralogs (12): SLC7A2 (ENSG00000003989), SLC7A14 (ENSG00000013293), SLC7A9 (ENSG00000021488), SLC7A8 (ENSG00000092068), SLC7A4 (ENSG00000099960), SLC7A6 (ENSG00000103064), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

Cystine/glutamate transporter — Q9UPY5 (reviewed: Q9UPY5)

Alternative names: Amino acid transport system xc-, Calcium channel blocker resistance protein CCBR1, Solute carrier family 7 member 11, xCT

All UniProt accessions (2): Q9UPY5, H0Y9F9

UniProt curated annotations — full annotation on UniProt →

Function. Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane. Provides L-cystine for the maintenance of the redox balance between extracellular L-cystine and L-cysteine and for the maintenance of the intracellular levels of glutathione that is essential for cells protection from oxidative stress. The transport is sodium-independent, electroneutral with a stoichiometry of 1:1, and is drove by the high intracellular concentration of L-glutamate and the intracellular reduction of L-cystine. Acts as an inhibitor of ferroptosis by mediating the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis. Also inhibits ferroptosis by acting as an atypical proton transporter that mediates a slow proton efflux from lysosomes via cystine and glutamate flux. Glutamate and cystine contain side-chain groups that are protonatable in the physiological range of lysosomal pH and cytosolic pH, respectively, enabling a slow lysosomal proton leak through a substrate-as-proton mechanism. Moreover, mediates N-acetyl-L-cysteine uptake into the placenta leading to subsequently down-regulation of pathways associated with oxidative stress, inflammation and apoptosis. In vitro can also transport L-aspartate. May participate in astrocyte and meningeal cell proliferation during development and can provide neuroprotection by promoting glutathione synthesis and delivery from non-neuronal cells such as astrocytes and meningeal cells to immature neurons. Controls the production of pheomelanin pigment directly.

Subunit / interactions. Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc; this interaction mediates cell membrane localization.

Subcellular location. Cell membrane. Lysosome membrane. Cell projection. Microvillus membrane.

Tissue specificity. Expressed in term placenta and primary term cytotrophoblast. Expressed mainly in the brain, but also in pancreas.

Post-translational modifications. Ubiquitinated by TRIM26; leading to proteasomal degradation.

Activity regulation. Inhibited by erastin and sulfasalazine. Inhibited by (S)-lactate. Inactivated by p-chloromercuribenzoic acid and p-chloromercuribenzenesulfonic acid.

Induction. By oxygen in a concentration-dependent manner. Up-regulated by S-nitroso-N-acetyl-D-penicillamine.

Similarity. Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.

RefSeq proteins (1): NP_055146* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR004760	L_AA_transporter	Family
IPR050598	AminoAcid_Transporter	Family

Pfam: PF13520

Catalyzed reactions (Rhea), 3 shown:

• L-cystine(out) + L-glutamate(in) = L-cystine(in) + L-glutamate(out) (RHEA:70995)
• an L-alpha-amino acid(in) + L-kynurenine(out) = an L-alpha-amino acid(out) + L-kynurenine(in) (RHEA:71191)
• N-acetyl-L-cysteine(out) + L-glutamate(in) = N-acetyl-L-cysteine(in) + L-glutamate(out) (RHEA:74567)

UniProt features (95 total): helix 23, mutagenesis site 22, topological domain 14, transmembrane region 12, turn 12, strand 5, binding site 2, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1, intramembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7EPZ	ELECTRON MICROSCOPY	3.4
7P9V	ELECTRON MICROSCOPY	3.4
7P9U	ELECTRON MICROSCOPY	3.7
7CCS	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPY5-F1	85.72	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 135; 244

Post-translational modifications (1): 26

Disulfide bonds (1): 158

Glycosylation sites (1): 314

Mutagenesis-validated functional residues (22):

Position	Phenotype
86	does not affect l-cystine transport activity; when associated with s-158; s-197; s-271; s-327; s-414 and s-435. does not
135	loss of l-cystine transport activity.
158	does not affect l-cystine transport activity; when associated with s-86; s-197; s-271; s-327; s-414 and s-435. does not
191	increases sensitivity to erastin-induced ferroptosis.
197	does not affect l-cystine transport activity; when associated with s-86; s-158; s-271; s-327; s-414 and s-435. does not
198	loss of l-cystine transport activity. does not affect location at the celle membrane. does not affect expression level.
254	increases resistance to erastin-induced ferroptosis. decreases sensitivity to erastin-induced inhibition of l-cystine tr
271	does not affect l-cystine transport activity; when associated with s-86; s-158; s-197; s-327; s-414 and s-435. does not
327	does not affect l-glutamate transport activity. does not affect location at cell membrane does not affect expression lev
327	loss of l-glutamate transport activity. does not affect location at cell membrane. does not affect expression level.
327	does not affect l-cystine transport activity; when associated with s-86; s-158; s-197; s-271; s-414 and s-435. does not
327	does not affect l-glutamate transport activity. does not affect location at cell membrane. does not affect expression le
336	decreases l-cystine transport activity about 50%. increases sensitivity to erastin-induced ferroptosis. significantly de
336	does not affect l-cystine transport activity.
388–389	decreased localization to lysosomes; when associated with s-409.
396	loss of l-cystine transport activity.
409	decreased localization to lysosomes; when associated with 388-a-a-389.
414	does not affect l-cystine transport activity; when associated with s-86; s-158; s-197; s-271; s-327 and s-435. does not
435	does not affect l-cystine transport activity; when associated with s-86; s-158; s-197; s-271; s-327 and s-414. does not

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes

MSigDB gene sets: 629 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_COGNITION, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VACUOLE_ORGANIZATION, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOCC_VACUOLAR_MEMBRANE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_ADULT_BEHAVIOR, GOBP_PLATELET_ACTIVATION

GO Biological Process (39): amino acid transmembrane transport (GO:0003333), glutathione metabolic process (GO:0006749), visual learning (GO:0008542), response to toxic substance (GO:0009636), L-cystine transport (GO:0015811), L-glutamate transmembrane transport (GO:0015813), ventricular system development (GO:0021591), striatum development (GO:0021756), adult behavior (GO:0030534), regulation of neutrophil apoptotic process (GO:0033029), cellular response to oxidative stress (GO:0034599), glutathione transmembrane transport (GO:0034775), lysosomal lumen pH elevation (GO:0035752), regulation of cell population proliferation (GO:0042127), regulation of melanin biosynthetic process (GO:0048021), lung alveolus development (GO:0048286), modulation of chemical synaptic transmission (GO:0050804), regulation of synapse organization (GO:0050807), regulation of protein transport (GO:0051223), response to redox state (GO:0051775), limb development (GO:0060173), platelet aggregation (GO:0070527), intracellular glutamate homeostasis (GO:0090461), L-glutamate import across plasma membrane (GO:0098712), negative regulation of ferroptosis (GO:0110076), dipeptide import across plasma membrane (GO:0140206), L-kynurenine transmembrane transport (GO:0140924), regulation of cellular response to oxidative stress (GO:1900407), obsolete regulation of cysteine metabolic process (GO:1901494), proton transmembrane transport (GO:1902600), regulation of glutathione biosynthetic process (GO:1903786), regulation of AMPA glutamate receptor clustering (GO:1904717), obsolete regulation of glutamate metabolic process (GO:2000211), amino acid transport (GO:0006865), brain development (GO:0007420), cellular response to stress (GO:0033554), regulation of programmed cell death (GO:0043067), transmembrane transport (GO:0055085), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (7): L-amino acid transmembrane transporter activity (GO:0015179), proton channel activity (GO:0015252), cystine:glutamate antiporter activity (GO:0015327), leak channel activity (GO:0022840), L-kynurenine transmembrane transporter activity (GO:0140926), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (9): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), brush border membrane (GO:0031526), microvillus membrane (GO:0031528), astrocyte projection (GO:0097449), cell projection (GO:0042995), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of amino acids	1
Nuclear events mediated by NFE2L2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transmembrane transport	2
L-alpha-amino acid transmembrane transport	2
anatomical structure development	2
cell projection membrane	2
amino acid transport	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
visual behavior	1
associative learning	1
response to chemical	1
sulfur amino acid transport	1
neutral amino acid transport	1
L-amino acid transport	1
modified amino acid transport	1
L-glutamate import	1
brain development	1
system development	1
subpallium development	1
behavior	1
neutrophil apoptotic process	1
regulation of immune system process	1
regulation of myeloid cell apoptotic process	1
regulation of leukocyte apoptotic process	1
response to oxidative stress	1
cellular response to chemical stress	1
glutathione transport	1
tripeptide transmembrane transport	1
intracellular pH elevation	1
cell population proliferation	1
regulation of cellular process	1
melanin biosynthetic process	1
regulation of secondary metabolite biosynthetic process	1
lung development	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
protein transport	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A11	SLC3A2	P08195	999
SLC7A11	CD44	P16070	985
SLC7A11	BECN1	Q14457	835
SLC7A11	GPX4	P36969	819
SLC7A11	TP53	P04637	711
SLC7A11	SLC1A2	P43004	694
SLC7A11	SLC1A5	Q15758	687
SLC7A11	ACSL4	O60488	676
SLC7A11	AIFM2	Q9BRQ8	664
SLC7A11	NFE2L2	Q16236	658
SLC7A11	GCLC	P48506	656
SLC7A11	GCLM	P48507	650
SLC7A11	SLC3A1	Q07837	633
SLC7A11	KEAP1	Q14145	611
SLC7A11	SLC1A1	P43005	603

IntAct

71 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
KRTAP1-3	SLC7A11	psi-mi:“MI:0915”(physical association)	0.560
SLC3A2	SLC7A11	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	SLC7A11	psi-mi:“MI:0915”(physical association)	0.560
SLC3A2	SLC7A11	psi-mi:“MI:0407”(direct interaction)	0.550
CD44	SLC7A11	psi-mi:“MI:0403”(colocalization)	0.540
CD44	SLC7A11	psi-mi:“MI:0915”(physical association)	0.540
SLC7A11	CD44	psi-mi:“MI:0915”(physical association)	0.540
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
EPHA2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
FADD	NUP42	psi-mi:“MI:0914”(association)	0.350
TRAF2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
NFE2L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NFE2L2	MYO1D	psi-mi:“MI:0914”(association)	0.350
CD44	SLC3A2	psi-mi:“MI:0914”(association)	0.350
KLRC2	CLGN	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
APOM	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC4E	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLRB1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (271): SLC7A11 (Proximity Label-MS), SLC7A11 (Affinity Capture-MS), SLC7A11 (Affinity Capture-MS), SLC7A11 (Proximity Label-MS), SLC7A11 (Proximity Label-MS), SLC7A11 (Affinity Capture-MS), SLC7A11 (Affinity Capture-MS), SLC7A11 (Affinity Capture-MS), SLC7A11 (Proximity Label-MS), SLC7A11 (Proximity Label-MS), SLC7A11 (Proximity Label-MS), SLC7A11 (Affinity Capture-Western), EGFR (Affinity Capture-Western), SLC3A2 (Affinity Capture-MS), OTUB1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3M3, A7MBD8, B3TP03, B5D5N9, D3ZMM8, O08812, O61369, P11170, P13866, P18581, P30823, P30825, P52569, P70423, P83740, Q01650, Q09143, Q1EHB4, Q22397, Q28I80, Q3ZMH1, Q49B93, Q59I64, Q5BL81, Q5PR34, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q6DCE8, Q7SYH5, Q7T384, Q7YQK4, Q8BGK6, Q8BYF6, Q8N695, Q8TCU3, Q8WY07, Q91WN3, Q92536

Diamond homologs: A1L3M3, D3ZMM8, O34739, P63115, P63116, P82251, P82252, Q01650, Q22397, Q28I80, Q59I64, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q7YQK4, Q8BGK6, Q8MH63, Q8TCU3, Q91WN3, Q92536, Q9GIP4, Q9N1Q4, Q9N1R6, Q9NS82, Q9QXA6, Q9QXW9, Q9R0S5, Q9UHI5, Q9UM01, Q9UPY5, Q9WTR6, Q9WVR6, Q9Z127, Q9Z1K8, Q8VIE6, A0JNI9, A8I499, B0UYF2, B3TP03

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
mTORC2	“down-regulates activity”	SLC7A11	phosphorylation
NFE2L2	“up-regulates quantity by expression”	SLC7A11	“transcriptional regulation”
hsa-miR-26a-5p	“down-regulates quantity by destabilization”	SLC7A11	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
DAP12 signaling	5	27.9×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
4:138183198:TCA:T	donor_loss	1.0000
4:138183199:CA:C	donor_loss	1.0000
4:138183200:ACCT:A	donor_loss	1.0000
4:138183201:C:CG	donor_loss	1.0000
4:138183301:AAGGT:A	acceptor_gain	1.0000
4:138183302:AGGT:A	acceptor_gain	1.0000
4:138183303:GGT:G	acceptor_gain	1.0000
4:138183304:GT:G	acceptor_gain	1.0000
4:138183306:C:CC	acceptor_gain	1.0000
4:138183306:CTAGT:C	acceptor_loss	1.0000
4:138185114:GACTT:G	donor_loss	1.0000
4:138185115:ACTT:A	donor_loss	1.0000
4:138185116:CTTAC:C	donor_loss	1.0000
4:138185117:T:TC	donor_loss	1.0000
4:138185118:T:TA	donor_loss	1.0000
4:138185119:A:AC	donor_gain	1.0000
4:138185120:C:CC	donor_gain	1.0000
4:138185120:C:CT	donor_loss	1.0000
4:138185120:CCA:C	donor_gain	1.0000
4:138185240:TGGTT:T	acceptor_gain	1.0000
4:138185242:GTTCT:G	acceptor_loss	1.0000
4:138185243:TT:T	acceptor_gain	1.0000
4:138185244:TCT:T	acceptor_loss	1.0000
4:138185245:C:CC	acceptor_gain	1.0000
4:138185245:C:T	acceptor_loss	1.0000
4:138185246:TGAAA:T	acceptor_loss	1.0000
4:138214577:CTACT:C	donor_loss	1.0000
4:138214578:TACTT:T	donor_loss	1.0000
4:138214579:ACTTA:A	donor_loss	1.0000
4:138214582:TAC:T	donor_loss	1.0000

AlphaMissense

3235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:138182361:A:G	L351P	0.997
4:138183202:C:A	R340M	0.997
4:138236347:A:G	W128R	0.997
4:138236347:A:T	W128R	0.997
4:138236357:A:C	F124L	0.997
4:138236357:A:T	F124L	0.997
4:138236359:A:G	F124L	0.997
4:138182373:C:G	R347P	0.996
4:138219267:A:G	W249R	0.996
4:138219267:A:T	W249R	0.996
4:138236361:G:T	A123D	0.996
4:138236406:C:T	G108E	0.996
4:138241823:A:G	W83R	0.996
4:138241823:A:T	W83R	0.996
4:138183202:C:G	R340T	0.995
4:138241881:G:C	F63L	0.995
4:138241881:G:T	F63L	0.995
4:138241883:A:G	F63L	0.995
4:138182310:G:T	A368D	0.994
4:138214617:G:C	N253K	0.994
4:138214617:G:T	N253K	0.994
4:138241894:C:T	G59E	0.994
4:138179282:C:T	G460E	0.993
4:138180675:C:G	R411P	0.993
4:138180718:A:G	W397R	0.993
4:138180718:A:T	W397R	0.993
4:138182379:G:T	A345E	0.993
4:138183240:G:C	C327W	0.993
4:138223305:A:C	N180K	0.993
4:138223305:A:T	N180K	0.993

dbSNP variants (sampled 300 via entrez): RS1000002068 (4:138168985 T>A), RS10000036 (4:138298108 C>T), RS1000008784 (4:138206680 C>A,T), RS1000014212 (4:138257282 T>C), RS1000039819 (4:138206212 C>A), RS1000058422 (4:138252398 C>T), RS1000063434 (4:138302530 T>G), RS1000072668 (4:138205775 A>C), RS1000102055 (4:138307004 T>C), RS1000115876 (4:138275476 A>T), RS10001990 (4:138237737 A>C,T), RS1000209931 (4:138219558 T>C), RS10002145 (4:138252173 G>A,C), RS1000227533 (4:138167971 A>G), RS1000233025 (4:138270844 C>A)

Disease associations

OMIM: gene MIM:607933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006940_143	Neurociticism	3.000000e-08
GCST008357_4	Mood instability	2.000000e-08
GCST012038_3	Sleep duration (> 10 hours)	1.000000e-08
GCST90002381_211	Eosinophil count	2.000000e-13
GCST90002382_106	Eosinophil percentage of white cells	3.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075149 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 806,876 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL863	CYSTEINE	4	733,144
CHEMBL1614646	SUSALIMOD	2	103

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC7 family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
imidazole ketone erastin	Inhibition	7.52	pIC50
quisqualate	Inhibition	5.3	pIC50

ChEMBL bioactivities

25 potent at pChembl≥5 of 49 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL3629669
8.00	IC50	10	nM	CHEMBL3629579
8.00	IC50	10	nM	CHEMBL3629668
8.00	IC50	10	nM	CHEMBL5571379
7.70	IC50	20	nM	CHEMBL3629578
7.52	IC50	30	nM	CHEMBL3629576
7.52	IC50	30	nM	CHEMBL3629671
7.52	IC50	30	nM	CHEMBL5564194
7.40	IC50	40	nM	CHEMBL3629577
7.22	IC50	60	nM	CHEMBL3629575
7.00	IC50	100	nM	CHEMBL3629670
7.00	IC50	100	nM	CHEMBL5590411
6.85	IC50	140	nM	ERASTIN
6.80	IC50	160	nM	SULFASALAZINE
6.70	IC50	200	nM	ERASTIN
6.52	IC50	300	nM	CHEMBL3629580
6.52	IC50	300	nM	CHEMBL5569941
6.10	IC50	800	nM	CHEMBL3629574
5.37	IC50	4300	nM	CHEMBL5394859
5.37	IC50	4300	nM	CHEMBL5395544
5.30	IC50	5000	nM	QUISQUALATE
5.30	IC50	5000	nM	CHEMBL94990

PubChem BioAssay actives

21 with measured affinity, of 160 total; 19 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-[2-[4-[(4-methoxyphenyl)methyl]piperazin-1-yl]acetyl]-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0040	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-morpholin-4-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0100	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[2-propan-2-yloxy-5-[2-(4-prop-2-enylpiperazin-1-yl)acetyl]phenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0100	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[4-(2-morpholin-4-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	2106962: Inhibition of Xc- in human HT-1080 cells assessed as decrease in glutamate release incubated for 2 hrs by Amplex red assay	ic50	0.0100	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[2-propan-2-yloxy-5-(2,2,2-trifluoroacetyl)phenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0200	uM
3-(5-acetyl-2-propan-2-yloxyphenyl)-2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0300	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[4-(2-imidazol-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	2106962: Inhibition of Xc- in human HT-1080 cells assessed as decrease in glutamate release incubated for 2 hrs by Amplex red assay	ic50	0.0300	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-imidazol-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0300	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-fluoroacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0400	uM
3-[2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-4-oxoquinazolin-3-yl]-4-propan-2-yloxybenzaldehyde	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.0600	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(2-piperazin-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.1000	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[4-(2-piperazin-1-ylacetyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	2106962: Inhibition of Xc- in human HT-1080 cells assessed as decrease in glutamate release incubated for 2 hrs by Amplex red assay	ic50	0.1000	uM
2-[1-[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]ethyl]-3-(2-ethoxyphenyl)quinazolin-4-one	1534338: Inhibition of cystine/glutamate antiporter system xc- in human Calu1 cells assessed as reduction in L-[3,3’-14C]-cystine uptake in presence of Na+ free uptake buffer by scintillation counting assay	ic50	0.1400	uM
2-hydroxy-5-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid	1534336: Inhibition of xCT-mediated cystein/glutamate transporter (unknown origin) assessed as reduction in L-[14C]cyctein uptake	ic50	0.1600	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-[2-(4-methylpiperazin-1-yl)acetyl]-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.3000	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[4-[2-(4-methylpiperazin-1-yl)acetyl]-2-propan-2-yloxyphenyl]quinazolin-4-one	2106962: Inhibition of Xc- in human HT-1080 cells assessed as decrease in glutamate release incubated for 2 hrs by Amplex red assay	ic50	0.3000	uM
2-[[4-[2-(4-chlorophenoxy)acetyl]piperazin-1-yl]methyl]-3-[5-(piperazin-1-ylmethyl)-2-propan-2-yloxyphenyl]quinazolin-4-one	1252343: Inhibition of Xct in human CCF-STTG1 cells assessed as glutamate release after 2 hrs by fluorometry	ic50	0.8000	uM
(2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)propanoic acid	475922: Inhibition of amino acid transport system xc-	ic50	5.0000	uM
4-[(S)-amino(carboxy)methyl]benzoic acid	475922: Inhibition of amino acid transport system xc-	ic50	5.0000	uM

CTD chemical–gene interactions

359 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, affects methylation, affects cotreatment, increases expression, decreases expression	16
ferrostatin-1	affects reaction, decreases expression, decreases reaction, increases expression, affects expression	10
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	10
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	10
bisphenol A	affects expression, increases expression, decreases expression	9
Benzo(a)pyrene	affects expression, decreases expression, increases expression	9
Cisplatin	decreases expression, decreases response to substance, increases expression, decreases reaction, affects reaction (+5 more)	9
Cyclosporine	increases expression	9
Arsenic Trioxide	increases expression, decreases response to substance	8
Tobacco Smoke Pollution	increases expression	7
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	7
methylmercuric chloride	increases expression, affects response to substance	6
Air Pollutants	increases expression, affects cotreatment, decreases expression, increases abundance	6
Arsenic	affects methylation, decreases expression, increases expression, affects cotreatment, increases abundance	6
lead acetate	increases expression, affects cotreatment	5
perfluorooctanoic acid	increases expression	5
Cadmium	increases abundance, increases expression, decreases expression	5
Tunicamycin	increases expression	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases expression	5
deoxynivalenol	decreases reaction, decreases expression, increases reaction	4
Acetaminophen	affects expression, affects cotreatment, increases expression	4
Deferoxamine	affects expression, affects reaction, decreases expression, decreases reaction	4
Hydrogen Peroxide	increases activity, increases uptake, affects expression, decreases expression, increases expression (+3 more)	4
Oxygen	increases expression, affects reaction, decreases expression, decreases abundance	4
Paraquat	decreases reaction, affects cotreatment, increases expression, decreases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression, decreases expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
cinnamaldehyde	increases expression	3
mono-(2-ethylhexyl)phthalate	decreases expression, increases expression, increases reaction	3

ChEMBL screening assays

72 unique, capped per target: 72 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1072817	Binding	Inhibition of amino acid transport system xc- in human SNB19 cells assessed as [3H]L-glutamate uptake at 250 uM by liquid scintillation counting	Isoxazole analogues bind the system xc- transporter: structure-activity relationship and pharmacophore model. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7V7	Abcam Hep-G2 SLC7A11 KO	Cancer cell line	Male
CVCL_D4QG	HCT116-SLC7A11-KO-c11	Cancer cell line	Male
CVCL_D8AK	Ubigene A-549 SLC7A11 KO	Cancer cell line	Male
CVCL_E0P1	Ubigene HeLa SLC7A11 KO	Cancer cell line	Female
CVCL_E1E5	Ubigene U-251 MG SLC7A11 KO	Cancer cell line	Male
CVCL_E1ER	Ubigene U-87 MG SLC7A11 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.