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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC15A2
solute carrier family 15 member 2
Chromosome 3 · 3q13.33
NCBI Gene: 6565Ensembl: ENSG00000163406.12HGNC: HGNC:10921UniProt: Q16348
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomephagocytic vesicle membranepeptide:proton symporter activitydipeptide import across plasma membraneallergic rhinitisEczematoid dermatitischronic kidney diseasekidney failure
✦AI Summary

SLC15A2 (PEPT2) is a proton-coupled oligopeptide transporter primarily responsible for the renal reabsorption of di- and tripeptides from glomerular filtrate 1. The transporter operates via a 2:1 or 3:1 proton-to-peptide stoichiometry and demonstrates substrate specificity for neutral and anionic dipeptides 12. Beyond peptide transport, SLC15A2 mediates uptake of pharmacologically important substrates including beta-lactam antibiotics like cefadroxil and amoxicillin, as well as carnosine, a dipeptide-like molecule with antioxidant properties 134. Mechanistically, the transporter recognizes diverse chemical scaffolds through a conserved binding pocket that accommodates antibiotic and drug substrates 3. Beyond nutrient absorption, SLC15A2 contributes to innate immunity by transporting bacterial peptidoglycans such as muramyl dipeptide (the NOD2 ligand) across cell membranes 5. Clinically, SLC15A2 variants associate with warfarin dose variability in Han-Chinese populations 6, and upregulation correlates with enhanced nephrotoxin sensitivity, as demonstrated by colistin-induced kidney injury that can be mitigated by cefadroxil competition 7. Recent evidence reveals SLC15A2 as a prognostic biomarker in prostate cancer, where reduced expression associates with biochemical recurrence and poor survival 8. Additionally, exercise-generated carnosine protects hematopoietic stem cells from radiation injury through SLC15A2-mediated transport and p53 inhibition 9.

Sources cited
1
SLC15A2 transports oligopeptides (2-4 amino acids) and beta-lactam antibiotics like cefadroxil
PMID: 16434549
2
SLC15A2 preference for dipeptides as primary substrate
PMID: 18367661
3
SLC15A2 renal absorption function for di- and tripeptides from glomerular filtrate
PMID: 7756356
4
SLC15A2 transports carnosine
PMID: 31073693
5
SLC15A2 mediates bacterial peptidoglycan transport including muramyl dipeptide (NOD2 ligand)
PMID: 20406817
6
Cryo-EM structures of SLC15A2/PepT2 in complex with cefadroxil, amoxicillin, and cloxacillin reveal antibiotic recognition mechanism and role of protonation
PMID: 39384780
7
SLC15A2 variants (rs1143671, rs1143672) associated with warfarin maintenance dose variability in Han-Chinese population
PMID: 29234073
8
SLC15A2 upregulation in CKD including diabetic nephropathy; cefadroxil targeting SLC15A2 protects from colistin nephrotoxicity
PMID: 39522761
9
SLC15A2 downregulation in prostate cancer associates with biochemical recurrence and decreased overall survival
PMID: 39740843
10
Exercise-generated carnosine transported via SLC15A2 protects hematopoietic stem cells from radiation injury through p53 inhibition
PMID: 39627813
Disease Associationsⓘ20
allergic rhinitisOpen Targets
0.39Weak
Eczematoid dermatitisOpen Targets
0.38Weak
chronic kidney diseaseOpen Targets
0.30Weak
kidney failureOpen Targets
0.30Weak
respiratory system diseaseOpen Targets
0.29Weak
autoimmune diseaseOpen Targets
0.29Weak
osteoarthritisOpen Targets
0.28Weak
asthmaOpen Targets
0.27Weak
allergic diseaseOpen Targets
0.26Weak
deep vein thrombosisOpen Targets
0.26Weak
Abnormal thrombosisOpen Targets
0.26Weak
atopic asthmaOpen Targets
0.13Weak
childhood onset asthmaOpen Targets
0.12Weak
nephrotic syndromeOpen Targets
0.08Suggestive
focal segmental glomerulosclerosisOpen Targets
0.08Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.08Suggestive
Balkan nephropathyOpen Targets
0.07Suggestive
nephronophthisisOpen Targets
0.06Suggestive
chronic myelogenous leukemiaOpen Targets
0.06Suggestive
nephrotic syndrome, IIa 26Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ABCC5Shared pathway23%SLC67A1Shared pathway22%SLC47A2Shared pathway22%SLC22A8Shared pathway22%SLC15A1Co-mentioned in literature20%ABCG2Shared pathway19%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
32%
Lung
32%
Heart
9%
Ovary
6%
Liver
5%
Gene Interaction Network
Click a node to explore
SLC15A2ABCC5SLC67A1SLC47A2SLC22A8SLC15A1ABCG2
PROTEIN STRUCTURE
Preparing viewer…
PDB6EZI · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.94 [0.76–1.15]
RankingsWhere SLC15A2 stands among ~20K protein-coding genes
  • #8,494of 20,598
    Most Researched53
  • #12,022of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedSLC15A2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SLC15A2 Serves as a Novel Prognostic Biomarker and Target for Prostate Cancer.
PMID: 39740843
Anticancer Res · 2024
1.00
2
Cefadroxil Targeting of SLC15A2/PEPT2 Protects From Colistin Nephrotoxicity.
PMID: 39522761
Lab Invest · 2025
0.90
3
Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis.
PMID: 39627813
Cell Commun Signal · 2024
0.80
4
Structural basis for antibiotic transport and inhibition in PepT2.
PMID: 39384780
Nat Commun · 2024
0.70
5
Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population.
PMID: 29234073
Sci Rep · 2017
0.60