SLC15A2 Gene

HGNC Family	Solute carriers (SLC)
Name	solute carrier family 15 (oligopeptide transporter), member 2
Description	The mammalian kidney expresses a proton-coupled peptide transporter that is responsible for the absorption of small peptides, as well as beta-lactam antibiotics and other peptide-like drugs, from the tubular filtrate. This transporter, SLC15A2, belongs to the same gene family as SLC15A1 (MIM 600544), the proton-coupled peptide transporter found in the small intestine (Liu et al, 1995 [PubMed 7756356]).[supplied by OMIM, Feb 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC15A2 encodes the high‑affinity, low‑capacity proton‐coupled di‑/tripeptide transporter known as PEPT2. This transporter is widely expressed in key tissues including the kidney, brain, lung, and other organs, where it contributes to the reabsorption of small peptides and the clearance of peptidomimetics. In many of these tissues, PEPT2 plays an essential role in maintaining physiological homeostasis by mediating the internalization of both endogenous peptides and drug compounds, as well as by contributing to the elimination of peptide‐like substrates from the cerebrospinal fluid."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variations in SLC15A2 critically affect PEPT2 transport activity and pharmacokinetic properties. Studies have demonstrated that common polymorphisms (such as the main variants hPEPT21 and 2, along with specific amino acid substitutions like R57H) can significantly alter kinetic parameters—including substrate affinity (Km), maximal transport velocity (Vmax), and pH sensitivity—without necessarily affecting membrane expression. Furthermore, chimera studies comparing related peptide transporters have helped delineate the domains that govern substrate specificity and transport efficiency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its basic function in peptide uptake, PEPT2 is implicated in a range of specialized biological processes. For instance, in epithelial cells of the respiratory tract and in phagocytes, PEPT2 facilitates the uptake of bacterial-derived dipeptides such as γ-iE-DAP, which in turn activate innate immune receptors (NOD1/NOD2), thereby linking peptide transport to host defense mechanisms. Aberrant or enhanced expression of PEPT2 has also been observed in certain cancers (e.g., prostate carcinoma), where its activity may be exploited for targeted drug delivery, and its genetic variants have been associated with differential responses to chemotherapeutic agents and altered drug disposition. Additionally, in the upper airway, nasal epithelium, and epidermal keratinocytes, PEPT2 contributes to the uptake of dietary peptides (e.g. anserine and carnosine), further underscoring its importance in both nutrient absorption and pharmacology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "I Rubio-Aliaga, H Daniel "}, {"type": "b", "children": [{"type": "t", "text": "Peptide transporters and their roles in physiological processes and drug disposition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Xenobiotica (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/00498250701875254"}], "href": "https://doi.org/10.1080/00498250701875254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18668438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18668438"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Julia Pinsonneault, Carsten Uhd Nielsen, Wolfgang Sadée "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of the human H+/dipeptide transporter PEPT2: analysis of haplotype functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.104.073098"}], "href": "https://doi.org/10.1124/jpet.104.073098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15282265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15282265"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ilka Knütter, Claudia Wollesky, Gabor Kottra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.108.143339"}], "href": "https://doi.org/10.1124/jpet.108.143339"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18713951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18713951"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tomohiro Terada, Megumi Irie, Masahiro Okuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variant Arg57His in human H+/peptide cotransporter 2 causes a complete loss of transport function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.02.063"}], "href": "https://doi.org/10.1016/j.bbrc.2004.02.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15020234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15020234"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Monica Sala-Rabanal, Donald D F Loo, Bruce A Hirayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00030.2008"}], "href": "https://doi.org/10.1152/ajprenal.00030.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18367661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18367661"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "F Döring, C Martini, J Walter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Importance of a small N-terminal region in mammalian peptide transporters for substrate affinity and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Membr Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00232-001-0135-9"}], "href": "https://doi.org/10.1007/s00232-001-0135-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11944083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11944083"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Peter W Swaan, Timothy Bensman, Praveen M Bahadduri, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification of Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated muramyl dipeptide transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.115584"}], "href": "https://doi.org/10.1074/jbc.M110.115584"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20406817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20406817"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wanyi Tai, Zhijin Chen, Kun Cheng "}, {"type": "b", "children": [{"type": "t", "text": "Expression profile and functional activity of peptide transporters in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharm (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/mp300364k"}], "href": "https://doi.org/10.1021/mp300364k"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22950754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22950754"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Remigius Agu, Elizabeth Cowley, Di Shao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proton-coupled oligopeptide transporter (POT) family expression in human nasal epithelium and their drug transport potential."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharm (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/mp100234z"}], "href": "https://doi.org/10.1021/mp100234z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21366347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21366347"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Praveen M Bahadduri, Vanessa M D'Souza, Julia K Pinsonneault, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of the peptide transporter PEPT2 in primary cultures of human upper airway epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2004-0322OC"}], "href": "https://doi.org/10.1165/rcmb.2004-0322OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15626774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15626774"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Christina Sobin, Mayra Gisel Flores-Montoya, Marisela Gutierrez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2009.07528.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2009.07528.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20067523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20067523"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Christina Sobin, Natali Parisi, Tanner Schaub, et al. "}, {"type": "b", "children": [{"type": "t", "text": "δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 and peptide transporter 2*2 haplotype may differentially mediate lead exposure in male children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Environ Contam Toxicol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00244-011-9645-3"}], "href": "https://doi.org/10.1007/s00244-011-9645-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21327641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21327641"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "David R Foster, Shiyin Yee, Barry E Bleske, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of interaction between the peptidomimetic substrates captopril and cephradine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0091270008329554"}], "href": "https://doi.org/10.1177/0091270008329554"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19246733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19246733"}]}]}]}
Synonyms	PEPT2
Proteins	S15A2_HUMAN
NCBI Gene ID	6565
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SLC15A2 has 6,324 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for SLC15A2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SLC15A2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by SLC15A2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC15A2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC15A2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SLC15A2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SLC15A2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SLC15A2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SLC15A2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC15A2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC15A2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SLC15A2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SLC15A2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC15A2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SLC15A2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SLC15A2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC15A2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SLC15A2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SLC15A2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SLC15A2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SLC15A2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SLC15A2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SLC15A2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SLC15A2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SLC15A2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SLC15A2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SLC15A2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SLC15A2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SLC15A2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SLC15A2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for SLC15A2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with SLC15A2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SLC15A2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SLC15A2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SLC15A2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SLC15A2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SLC15A2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for SLC15A2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SLC15A2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SLC15A2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SLC15A2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SLC15A2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.