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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC38A2
solute carrier family 38 member 2
Chromosome 12 · 12q13.11
NCBI Gene: 54407Ensembl: ENSG00000134294.15HGNC: HGNC:13448UniProt: Q8NHT5
110PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cellular response to arsenite(3-)regulation of cellular response to stresspositive regulation of gene expressionprotein bindingAbnormality of the skeletal systemuterine fibroidAbruptio PlacentaeUterine leiomyoma
✦AI Summary

SLC38A2 is a sodium-dependent neutral amino acid symporter that mediates cotransport of amino acids and sodium ions across the plasma membrane with 1:1 stoichiometry 12. The transporter functions at critical physiological barriers, including the blood-brain barrier and placenta 12, and plays specialized roles in glutamine homeostasis and bone development through proline transport. Mechanistically, SLC38A2 exhibits pH-sensitive, electrogenic transport driven by the sodium electrochemical gradient and is intolerant to lithium 1. Protein stability is regulated through ubiquitination-mediated membrane localization, with monoubiquitination at lysine 59 suppressing endocytosis 3. The transporter's expression is tightly controlled by transcriptional regulators and inflammatory signaling pathways 45. Clinically, SLC38A2 dysregulation is implicated in multiple pathologies. In hypertension, SLC38A2 inhibition lowers blood pressure by modulating endothelial nitric oxide signaling through glutamine uptake regulation; the rs1873793 variant associates with hypertension risk 6. In cancer, SLC38A2 upregulation promotes glutamine addiction in lung adenocarcinoma and bladder cancer metastasis 43, while brain metastasis involves miR-199b-5p-mediated SLC38A2 downregulation in neurons to reprogram neural metabolism 7. ARID1A-mutant ovarian cancers exhibit SLC38A2 dependence exploitable therapeutically 8. In allergic rhinitis, SLC38A2 mediates alanine uptake by dendritic cells through CD169+ macrophage signaling 9.

Sources cited
1
SLC38A2 is a sodium-dependent neutral amino acid symporter that mediates cotransport of amino acids and sodium ions across the plasma membrane with 1:1 stoichiometry , .
PMID: 10930503
2
Protein stability is regulated through ubiquitination-mediated membrane localization, with monoubiquitination at lysine 59 suppressing endocytosis .
PMID: 38949026
3
In hypertension, SLC38A2 inhibition lowers blood pressure by modulating endothelial nitric oxide signaling through glutamine uptake regulation; the rs1873793 variant associates with hypertension risk .
PMID: 40901922
4
In cancer, SLC38A2 upregulation promotes glutamine addiction in lung adenocarcinoma and bladder cancer metastasis , , while brain metastasis involves miR-199b-5p-mediated SLC38A2 downregulation in neurons to reprogram neural metabolism .
PMID: 38811525
5
ARID1A-mutant ovarian cancers exhibit SLC38A2 dependence exploitable therapeutically .
PMID: 40658600
6
In allergic rhinitis, SLC38A2 mediates alanine uptake by dendritic cells through CD169+ macrophage signaling .
PMID: 39435598
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.52Moderate
uterine fibroidOpen Targets
0.38Weak
Abruptio PlacentaeOpen Targets
0.32Weak
Uterine leiomyomaOpen Targets
0.30Weak
hair colorOpen Targets
0.28Weak
alcohol drinkingOpen Targets
0.27Weak
epilepsyOpen Targets
0.25Weak
lymphatic system diseaseOpen Targets
0.22Weak
Varicose veinsOpen Targets
0.22Weak
atrial fibrillationOpen Targets
0.21Weak
vein disorderOpen Targets
0.20Weak
Respiratory insufficiencyOpen Targets
0.20Weak
pneumoconiosisOpen Targets
0.19Weak
nerve plexus diseaseOpen Targets
0.18Weak
Abnormality of the breastOpen Targets
0.17Weak
HypercholesterolemiaOpen Targets
0.17Weak
Parkinson diseaseOpen Targets
0.16Weak
breast cancerOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
fetal growth restrictionOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SCN11AProtein interaction77%PBX2Protein interaction76%AANATProtein interaction72%SLC3A2Protein interaction71%SLC1A5Protein interaction60%SLC38A1Protein interaction57%
Tissue Expression6 tissues
Liver
100%
Lung
96%
Ovary
77%
Bone Marrow
76%
Brain
52%
Heart
46%
Gene Interaction Network
Click a node to explore
SLC38A2SCN11APBX2AANATSLC3A2SLC1A5SLC38A1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NHT5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.31Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.31]
RankingsWhere SLC38A2 stands among ~20K protein-coding genes
  • #4,333of 20,598
    Most Researched110 · top quartile
  • #1,205of 17,882
    Most Constrained (LOEUF)0.31 · top 10%
Genes detectedSLC38A2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis.
PMID: 23459753
J Physiol · 2013
1.00
2
Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma.
PMID: 36209111
J Hematol Oncol · 2022
0.90
3
UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.
PMID: 38949026
J Clin Invest · 2024
0.80
4
Inhibiting SLC38A2 lowers blood pressure in rodent models of hypertension.
PMID: 40901922
Sci Transl Med · 2025
0.70
5
Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis.
PMID: 38811525
Nat Commun · 2024
0.60