SLC15A1

Summary

SLC15A1 (solute carrier family 15 member 1, HGNC:10920) is a protein-coding gene on chromosome 13q32.2-q32.3, encoding Solute carrier family 15 member 1 (P46059). Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides.

This gene encodes an intestinal hydrogen peptide cotransporter that is a member of the solute carrier family 15. The encoded protein is localized to the brush border membrane of the intestinal epithelium and mediates the uptake of di- and tripeptides from the lumen into the enterocytes. This protein plays an important role in the uptake and digestion of dietary proteins. This protein also facilitates the absorption of numerous peptidomimetic drugs.

Source: NCBI Gene 6564 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 120 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10920
Approved symbol	SLC15A1
Name	solute carrier family 15 member 1
Location	13q32.2-q32.3
Locus type	gene with protein product
Status	Approved
Aliases	PEPT1, HPECT1, HPEPT1
Ensembl gene	ENSG00000088386
Ensembl biotype	protein_coding
OMIM	600544
Entrez	6564

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000376494, ENST00000376503, ENST00000856774

RefSeq mRNA: 1 — MANE Select: NM_005073 NM_005073

CCDS: CCDS9489

Canonical transcript exons

ENST00000376503 — 23 exons

Exon	Start	End
ENSE00000514905	98719237	98719320
ENSE00000514907	98712498	98712584
ENSE00000514908	98711854	98711943
ENSE00000514911	98709572	98709660
ENSE00000514912	98708686	98708767
ENSE00000514914	98704289	98704435
ENSE00000685589	98706134	98706253
ENSE00000685602	98709742	98709774
ENSE00000685604	98709867	98709911
ENSE00000685610	98715878	98715960
ENSE00000917019	98686190	98686297
ENSE00000940168	98687581	98687724
ENSE00001007056	98688248	98688356
ENSE00001007057	98688470	98688577
ENSE00001007058	98702480	98702529
ENSE00001270728	98721495	98721585
ENSE00001470740	98683801	98684915
ENSE00001693958	98726368	98726449
ENSE00001771719	98726843	98726859
ENSE00001820228	98752595	98752672
ENSE00003459536	98726123	98726264
ENSE00003548630	98723912	98724031
ENSE00003619732	98721804	98721903

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 96.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.3772 / max 523.3990, expressed in 136 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137945	1.3059	120
137948	0.0474	20
137946	0.0163	4
137947	0.0076	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	96.35	gold quality
jejunal mucosa	UBERON:0000399	95.30	gold quality
ileal mucosa	UBERON:0000331	93.98	gold quality
gall bladder	UBERON:0002110	93.45	gold quality
mammalian vulva	UBERON:0000997	87.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.36	gold quality
small intestine	UBERON:0002108	86.72	gold quality
skin of abdomen	UBERON:0001416	86.41	gold quality
upper arm skin	UBERON:0004263	86.00	gold quality
upper leg skin	UBERON:0004262	85.81	gold quality
skin of leg	UBERON:0001511	85.38	gold quality
lower esophagus mucosa	UBERON:0035834	85.31	gold quality
zone of skin	UBERON:0000014	84.32	gold quality
right lobe of liver	UBERON:0001114	83.22	gold quality
penis	UBERON:0000989	82.28	gold quality
buccal mucosa cell	CL:0002336	81.71	gold quality
body of pancreas	UBERON:0001150	80.41	gold quality
liver	UBERON:0002107	80.38	gold quality
jejunum	UBERON:0002115	79.21	gold quality
pancreas	UBERON:0001264	78.18	gold quality
islet of Langerhans	UBERON:0000006	76.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.79	silver quality
diaphragm	UBERON:0001103	74.38	gold quality
frontal pole	UBERON:0002795	73.60	silver quality
endometrium epithelium	UBERON:0004811	73.16	gold quality
caput epididymis	UBERON:0004358	72.17	gold quality
paraflocculus	UBERON:0005351	72.10	silver quality
hair follicle	UBERON:0002073	72.01	silver quality
adult mammalian kidney	UBERON:0000082	71.94	gold quality
middle frontal gyrus	UBERON:0002702	71.82	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	37.04
E-ANND-3	yes	16.42
E-MTAB-6678	yes	9.21
E-ENAD-27	yes	6.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX2, CREB1, NFE2L2, PPARA, SP1

miRNA regulators (miRDB)

36 targeting SLC15A1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-496	98.66	69.80	931
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-649	97.96	67.21	704
HSA-MIR-6818-5P	97.50	67.10	1167

Literature-anchored findings (GeneRIF, showing 40)

• 3,5,3’-L-triiodothyronine regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells. (PMID:11897620)
• the two identified aminoterminal regions in mammalian peptide carriers play an important role in determining the substrate affinity and also other characteristic features of the two transporter subtypes. (PMID:11944083)
• Hormonal regulation of this transporter in Caco-2 cells with normal and anoxia/reoxygenation management. (PMID:12679938)
• role of transmembrane segment 5 of hPepT1, the most conserved segment across different species, in forming a part of the aqueous substrate translocation pathway (PMID:12788085)
• the extracellular end of TMS7 may shift following substrate binding, providing the basis for channel opening and substrate translocation (PMID:14532279)
• Wealth of new information on regulation of key transporter in intestine. Useful applications in nutritional and pharmacological treatments. Review. (PMID:14561585)
• hPepT1 is able to bind protons at a relatively basic pH, resulting in facilitation of transport of Gly-Sar by hPepT1 at higher pH (PMID:14725353)
• hPepT1 expression in colonic inflammation is increased which plays an important role in promoting participation in host defense. (PMID:15521010)
• Ala-Gln, but not somatropin, maintained cellular glutathione and prevented the decrease in PepT1 protein expression. (PMID:15623827)
• the inferred mechanisms are able to sufficiently interpret the transport of both neutral and charged substrates by PEPT1 (PMID:15802293)
• PepT1 is a transporter of proven pharmaceutical utility for enhancing oral absorption. (PMID:15832502)
• Transfected hPepT1 cell line may serve as a useful in vitro model for screening and quantifying peptide and peptide-like drug transport (PMID:15832510)
• Identification of regions which are crucial for the interaction between peptidomimetics and PEPT1. (PMID:15974593)
• functionalities of PEPT1 and PEPT2 were largely conserved in terms of glycylsarcosine uptake kinetics and inhibitor specificity (PMID:15981923)
• PEPT1 mediates oligopeptide-induced hormone secretion in enteroendocrine cells. (PMID:16181611)
• Functional PepT1 recovers efficiently in a budded virus fraction and this expression system will be a useful tool for characterization and screening of peptide-mimetic drugs in drug discovery. (PMID:16198124)
• PEPT1 is expressed and functional in MKN45 cells; function of PEPT1 is unaffected by cellular injury induced by fluorouracil (PMID:16253763)
• model can simulate Gly-Sar transport in cells expressing PEPT1 at different levels (PMID:16283203)
• Tumor necrosis factor-alpha and interferon-gamma increased the expression of PepT1 protein in a concentration- and time-dependent fashion. (PMID:16328452)
• hPepT1 is expressed in macrophages, where the transporter functions best at the physiological pH 7.2. hPepT1-mediates fMLP transport, which might constitute a novel immune cell activation pathway during intestinal inflammation. (PMID:16568107)
• The common hPEPT1 single-nucleotide polymorphisms Ser117Asn and Gly419Ala retained the essential kinetic and drug recognition characteristics of the wild type, suggesting that neither variant is likely to have a major impact on oral absorption of drugs. (PMID:16627568)
• leptin, which is increased in inflamed colonic mucosa, triggers colonic expression of hPepT1 via the CREB and Cdx2 transcription factors (PMID:16963449)
• our results are consistent with a salt bridge between R282 and D341 in hPepT1, and we use these and other data to propose a role for the R282-D341 charge pair in the hPepT1 translocation mechanism (PMID:17009102)
• The strategy behind the present work is that by linking a suitable di- or tripeptidic promoiety to a drug substance, by a hydrolysable ester bond, it may give rise to a prodrug that targets hPEPT1. (PMID:17407174)
• Acetaldehyde significantly modulates PEPT1 function and thereby affects drug bioavailability. (PMID:18028524)
• Results indicate that Gly-Sar uptake and transport in Calu-3 cells are hPEPT1-mediated rather than hPEPT2-mediated. (PMID:18094991)
• ethanol significantly reduced transport of dipeptides via a reduction in transport capacity, rather than competing for binding sites in hPepT1 (PMID:18336632)
• Review summarizes current knowledge on the functional and phenotypic consequences of genetic variation in intestinally, hepatically and renally expressed members of the peptide transporter-1 (SLC15) family. (PMID:18466105)
• PEPT1 exhibits ectopic expression in colonic inflammation (PMID:18668438)
• there are no major differences in the substrate recognition pattern of hPEPT1 and rPEPT2 with regard to the ACE inhibitors tested. (PMID:18713951)
• diet-induced obesity, that a 4-week hypercaloric diet resulted in a 46% decrease in PepT1-specific transport, because of a 30% decrease in PepT1 protein and a 50% decrease in PepT1 mRNA levels. (PMID:19144638)
• hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans (PMID:19246733)
• Report morphological adaptation with preserved proliferation/PepT1 content in the colon of patients with short bowel syndrome. (PMID:19389806)
• Results suggest that oseltamivir is a substrate of PEPT1 and that PEPT1 is involved in its intestinal absorption. (PMID:19439487)
• Single Nucleotide Polymorphisms in SLC15A1 is associated with inflammatory bowel disease. (PMID:19462432)
• Demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation. (PMID:19549526)
• Results suggest that Gly594 and Glu595 in transmembrane domain 10 of hPEPT1 have key roles in substrate transport and that Tyr588 may have an important secondary mechanistic role. (PMID:19685173)
• We conclude that anserine and carnosine interact with the human intestinal peptide transporter and are transported by hPEPT1 in an active, electrogenic H(+) symport. (PMID:20067523)
• Pyrraline containing dipeptides are transported by human PEPT1 in an electrogenic manner into intestinal cells. (PMID:20104847)
• AMP-activated protein kinase provides a link between the hPepT1 transporter and the metabolic state of Caco-2 cells. (PMID:20430871)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc15a1b	ENSDARG00000044528
danio_rerio	slc15a1a	ENSDARG00000100315
mus_musculus	Slc15a1	ENSMUSG00000025557
rattus_norvegicus	Slc15a1	ENSRNOG00000011598

Paralogs (4): SLC15A3 (ENSG00000110446), SLC15A4 (ENSG00000139370), SLC15A2 (ENSG00000163406), SLC15A5 (ENSG00000188991)

Protein

Protein identifiers

Solute carrier family 15 member 1 — P46059 (reviewed: P46059)

Alternative names: Intestinal H(+)/peptide cotransporter, Oligopeptide transporter, small intestine isoform, Peptide transporter 1

All UniProt accessions (2): P46059, B2CQT6

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1. Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen. Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system.

Subunit / interactions. Interacts (via extracellular domain region) with trypsin.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed in small intestine.

Domain organisation. The extracellular domain (ECD) region specifically binds trypsin.

Similarity. Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.

RefSeq proteins (1): NP_005064* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000109	POT_fam	Family
IPR004768	Oligopep_transport	Family
IPR018456	PTR2_symporter_CS	Conserved_site
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00854

Catalyzed reactions (Rhea), 12 shown:

• a dipeptide(out) + H(+)(out) = a dipeptide(in) + H(+)(in) (RHEA:64392)
• glycyl-sarcosine(out) + H(+)(out) = glycyl-sarcosine(in) + H(+)(in) (RHEA:64396)
• an L-amino acid tripeptide(out) + H(+)(out) = an L-amino acid tripeptide(in) + H(+)(in) (RHEA:64400)
• carnosine(out) + H(+)(out) = carnosine(in) + H(+)(in) (RHEA:64404)
• N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(out) + 2 H(+)(out) = N-acetyl-D-muramoyl-L-alanyl-D-isoglutamine(in) + 2 H(+)(in) (RHEA:64408)
• L-alanyl-L-proline(out) + H(+)(out) = L-alanyl-L-proline(in) + H(+)(in) (RHEA:64420)
• L-leucyl-L-proline(out) + H(+)(out) = L-leucyl-L-proline(in) + H(+)(in) (RHEA:64424)
• glycyl-L-proline(out) + H(+)(out) = glycyl-L-proline(in) + H(+)(in) (RHEA:64428)
• L-alanyl-L-prolylglycine(out) + H(+)(out) = L-alanyl-L-prolylglycine(in) + H(+)(in) (RHEA:64432)
• glycylglycyl-L-isoleucine(out) + H(+)(out) = glycylglycyl-L-isoleucine(in) + H(+)(in) (RHEA:64436)
• glycylglycyl-L-proline(out) + H(+)(out) = glycylglycyl-L-proline(in) + H(+)(in) (RHEA:64440)
• glycyl-L-glutamine(out) + H(+)(out) = glycyl-L-glutamine(in) + H(+)(in) (RHEA:71671)

UniProt features (102 total): helix 28, strand 18, transmembrane region 12, topological domain 12, sequence variant 10, mutagenesis site 8, glycosylation site 7, turn 5, chain 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7PMX	ELECTRON MICROSCOPY	3.5
7PN1	ELECTRON MICROSCOPY	3.9
7PMW	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46059-F1	87.04	0.50

Functional residue map

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

Glycosylation sites (7): 50, 404, 408, 439, 509, 514, 562

Mutagenesis-validated functional residues (8):

Position	Phenotype
573	does not affect peptide transporter activity.
588	reduced peptide transporter activity.
594	does not affect peptide transporter activity.
594	nearly abolished peptide transporter activity.
594	abolished peptide transporter activity.
595	nearly abolished peptide transporter activity.
595	does not affect peptide transporter activity.
595	abolished peptide transporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-427975	Proton/oligopeptide cotransporters
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 152 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, MORF_ITGA2, MODULE_162, MORF_RAD51L3, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_368, MORF_CTSB, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, MORF_IL4, MORF_PRKCA, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, MORF_THPO, GOCC_APICAL_PLASMA_MEMBRANE, SABATES_COLORECTAL_ADENOMA_DN, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (8): monoatomic ion transport (GO:0006811), protein transport (GO:0015031), dipeptide import across plasma membrane (GO:0140206), tripeptide import across plasma membrane (GO:0140207), oligopeptide transport (GO:0006857), peptide transport (GO:0015833), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (7): proton-dependent oligopeptide secondary active transmembrane transporter activity (GO:0005427), peptide:proton symporter activity (GO:0015333), tripeptide transmembrane transporter activity (GO:0042937), dipeptide transmembrane transporter activity (GO:0071916), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), oligopeptide transmembrane transporter activity (GO:0035673)

GO Cellular Component (4): plasma membrane (GO:0005886), brush border (GO:0005903), membrane (GO:0016020), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of oligopeptides	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	4
dipeptide transmembrane transport	2
oligopeptide import across plasma membrane	2
secondary active transmembrane transporter activity	2
oligopeptide transmembrane transporter activity	2
apical part of cell	2
intracellular protein localization	1
establishment of protein localization	1
tripeptide transmembrane transport	1
peptide transport	1
nitrogen compound transport	1
cellular process	1
monoatomic cation transmembrane transport	1
solute:proton symporter activity	1
peptide transmembrane transporter activity	1
tripeptide transport	1
transporter activity	1
transmembrane transport	1
transmembrane transporter activity	1
oligopeptide transmembrane transport	1
membrane	1
cell periphery	1
microvillus	1
cluster of actin-based cell projections	1
cellular anatomical structure	1
plasma membrane region	1

Protein interactions and networks

STRING

1606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC15A1	SLC5A1	P13866	800
SLC15A1	SLC1A1	P43005	718
SLC15A1	SLC2A2	P11168	706
SLC15A1	SLC22A6	Q4U2R8	704
SLC15A1	ABCC2	Q92887	702
SLC15A1	SLCO2B1	O94956	696
SLC15A1	SLC22A5	O76082	672
SLC15A1	SLC2A5	P22732	645
SLC15A1	GPRC6A	Q5T6X5	644
SLC15A1	ABCG2	Q9UNQ0	644
SLC15A1	SLC9A3	P48764	643
SLC15A1	SLC22A8	Q8TCC7	643
SLC15A1	SLC6A19	Q695T7	641
SLC15A1	ACE	P12821	638
SLC15A1	SLC3A1	Q07837	634

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
CLPB	CLUH	psi-mi:“MI:0914”(association)	0.530
SLC15A1	LCMT2	psi-mi:“MI:0914”(association)	0.350
SLC15A1	MEN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (148): TAMM41 (Affinity Capture-MS), C4A (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), PTPLA (Affinity Capture-MS), FAM127A (Affinity Capture-MS), SLC25A24 (Affinity Capture-MS), PDS5B (Affinity Capture-MS), SLC25A28 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), CDYL (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), RAB3A (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), PXMP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ILB2, A0A8M9Q308, A2CER7, A2SWM2, A2ZN77, A4FV52, A8WGF7, B0S6T2, O23596, O62786, P11170, P30638, P36836, P46029, P46059, P51574, P60815, Q05B21, Q0ILJ3, Q10R54, Q16348, Q1L8X9, Q28FF3, Q3TXX4, Q5M7K3, Q5XGK0, Q62634, Q63424, Q6INC8, Q7TSF2, Q7ZU13, Q8AVC3, Q8BFU8, Q8TDB8, Q8WMX5, Q91X85, Q9C5L3, Q9C8X2, Q9ES07, Q9FE59

Diamond homologs: A0A2R9TD79, A1JRI8, A2RMA8, B6VMU9, O07380, P0C2U2, P0C2U3, P36836, P46059, P51574, P75742, P94408, Q83S84, Q8WMX5, Q8X9D3, Q9JIP7, A6T6E2, A8AJB3, B0S6T2, B5XZE5, C0PWD2, D0ZQC5, D2TNL4, P39276, P46029, P91679, Q16348, Q17758, Q21219, Q57RM6, Q63424, Q7CQY0, Q9ES07, O01840, Q0WP01, Q0WSZ6, Q84WG0, Q8GFA2, Q93Z20, Q9M817

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLC15A1	“up-regulates activity”	“muramyl dipeptide”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3578 predictions. Top by Δscore:

Variant	Effect	Δscore
13:98684939:C:CT	acceptor_gain	1.0000
13:98684940:A:T	acceptor_gain	1.0000
13:98686184:CCATA:C	donor_loss	1.0000
13:98686185:CATA:C	donor_loss	1.0000
13:98686186:ATAC:A	donor_loss	1.0000
13:98686187:TA:T	donor_loss	1.0000
13:98686188:A:C	donor_loss	1.0000
13:98686189:C:G	donor_loss	1.0000
13:98687597:T:TA	donor_gain	1.0000
13:98687624:TCGCC:T	donor_gain	1.0000
13:98688468:A:AC	donor_gain	1.0000
13:98688468:ACATG:A	donor_gain	1.0000
13:98688469:C:CC	donor_gain	1.0000
13:98688469:CATG:C	donor_gain	1.0000
13:98688469:CATGC:C	donor_gain	1.0000
13:98702476:ATAC:A	donor_loss	1.0000
13:98702477:TA:T	donor_loss	1.0000
13:98702478:A:AC	donor_gain	1.0000
13:98702478:ACCTG:A	donor_loss	1.0000
13:98702479:C:A	donor_loss	1.0000
13:98702479:C:CC	donor_gain	1.0000
13:98702529:CCTGA:C	acceptor_loss	1.0000
13:98702530:CTG:C	acceptor_loss	1.0000
13:98704288:CCA:C	donor_gain	1.0000
13:98704375:C:CT	acceptor_gain	1.0000
13:98704376:A:T	acceptor_gain	1.0000
13:98704431:TTTGT:T	acceptor_gain	1.0000
13:98704432:TTGT:T	acceptor_gain	1.0000
13:98704433:TGT:T	acceptor_gain	1.0000
13:98704434:GT:G	acceptor_gain	1.0000

AlphaMissense

4709 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:98709902:A:G	W304R	0.999
13:98709902:A:T	W304R	0.999
13:98686239:C:A	G629V	0.998
13:98686261:A:G	W622R	0.998
13:98686261:A:T	W622R	0.998
13:98687594:A:G	F605S	0.998
13:98708719:A:C	F372L	0.998
13:98708719:A:T	F372L	0.998
13:98708721:A:G	F372L	0.998
13:98709890:C:G	A308P	0.998
13:98721529:A:C	S174R	0.998
13:98721529:A:T	S174R	0.998
13:98721531:T:G	S174R	0.998
13:98721533:C:T	G173E	0.998
13:98721562:A:C	F163L	0.998
13:98721562:A:T	F163L	0.998
13:98721564:A:G	F163L	0.998
13:98721849:T:A	K140N	0.998
13:98721849:T:G	K140N	0.998
13:98721859:C:T	G137E	0.998
13:98721865:C:T	G135E	0.998
13:98721866:C:A	G135W	0.998
13:98726179:G:C	C63W	0.998
13:98726390:T:A	R27S	0.998
13:98726390:T:G	R27S	0.998
13:98726393:T:A	E26D	0.998
13:98726393:T:G	E26D	0.998
13:98686240:C:G	G629R	0.997
13:98687593:G:C	F605L	0.997
13:98687593:G:T	F605L	0.997

dbSNP variants (sampled 300 via entrez): RS1000066284 (13:98707469 G>C), RS1000099451 (13:98728312 A>G), RS1000326544 (13:98690057 G>A,T), RS1000457721 (13:98742116 A>C,G), RS1000476521 (13:98684142 T>C), RS1000612099 (13:98747462 A>G), RS1000622115 (13:98709012 G>A), RS1000673456 (13:98696283 A>C,G), RS1000684029 (13:98736729 C>A,G,T), RS1000836422 (13:98702994 G>A,T), RS1000908396 (13:98752494 G>T), RS1001104137 (13:98752629 C>T), RS1001119037 (13:98736995 A>G,T), RS1001136253 (13:98715665 C>G,T), RS1001185535 (13:98739814 T>C)

Disease associations

OMIM: gene MIM:600544 | 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
GCST001533_11	Immune reponse to smallpox (secreted IL-1beta)	3.000000e-08
GCST002598_68	Educational attainment	3.000000e-07
GCST004033_18	QRS interval (sulfonylurea treatment interaction)	2.000000e-07
GCST005986_19	Blood urea nitrogen levels	1.000000e-13
GCST010002_194	Refractive error	2.000000e-76

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004784	self reported educational attainment
EFO:0007922	response to sulfonylurea

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4605 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,133 (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
CHEMBL1604	CEPHRADINE	4	20,133

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8001466	SLC15A1		0.00	0
rs1339067	SLC15A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC15 family of peptide transporters

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
Lys[Z(NO2)]-Val	Inhibition	5.7	pKi
Lys[Z(NO2)]-Pro	Inhibition	5.3	pKi
Lys[Z(NO2)]-Lys[Z(NO2)]	Inhibition	4.9	pKi
4-AMBA	Inhibition	2.3	pKi

ChEMBL bioactivities

9 potent at pChembl≥5 of 71 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	IC50	180	nM	CHEMBL429950
6.75	Ki	180	nM	CHEMBL429950
6.70	IC50	200	nM	CHEMBL417979
6.70	Ki	200	nM	CHEMBL417979
6.40	IC50	400	nM	CHEMBL10650
6.40	Ki	400	nM	CHEMBL10650
5.01	Ki	9800	nM	CEPHRADINE
5.00	Ki	1e+04	nM	CHEMBL190869
5.00	Ki	1e+04	nM	CHEMBL156844

PubChem BioAssay actives

9 with measured affinity, of 958 total; 6 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
(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]propanoic acid	92024: Concentration required to inhibit the maximum [14C]Gly-Sar uptake by human Intestinal peptide transporter PepT1 in Caco-2 cells	ic50	0.1800	uM
2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetic acid	92024: Concentration required to inhibit the maximum [14C]Gly-Sar uptake by human Intestinal peptide transporter PepT1 in Caco-2 cells	ic50	0.2000	uM
(5S)-5-amino-4-oxo-6-phenylhexanoic acid	92024: Concentration required to inhibit the maximum [14C]Gly-Sar uptake by human Intestinal peptide transporter PepT1 in Caco-2 cells	ic50	0.4000	uM
(6R,7R)-7-[[(2R)-2-amino-2-cyclohexa-1,4-dien-1-ylacetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	681115: TP_TRANSPORTER: inhibition of Gly-Sar uptake (pH6.0) in Caco-2 cells	ki	9.8000	uM
2-[[2-amino-3-(4-phenylmethoxyphenyl)propanoyl]amino]propanoic acid	92023: Inhibition constant (Ki) for human intestinal peptide carrier	ki	10.0000	uM
(2S)-2-[[(2S)-2-amino-3-(4-phenylphenyl)propanoyl]amino]propanoic acid	238858: Binding affinity against membrane transport protein PEPT1 in human Caco-2 cells	ki	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
glycylsarcosine	decreases reaction, increases uptake, increases transport, decreases activity, decreases uptake	5
pirinixic acid	affects binding, decreases expression, increases activity, increases expression	2
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tobacco Smoke Pollution	affects expression	2
Zinc	affects binding, decreases reaction, decreases uptake, decreases activity	2
Cyclosporine	decreases expression	2
methyleugenol	decreases expression	1
terbufos	increases methylation	1
phenylalanylserine	affects binding	1
benzo(e)pyrene	increases methylation	1
AICA ribonucleotide	decreases activity	1
cinnabar	decreases expression, affects transport	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
benazepril	decreases reaction, increases uptake	1
mifobate	decreases reaction, increases activity, increases expression	1
trandolapril	decreases reaction, increases uptake	1
spirapril	decreases reaction, increases uptake	1
quinaprilat	decreases reaction, increases uptake	1
moexipril	decreases reaction, increases uptake	1
repaglinide	decreases activity	1
JBP 485	affects binding, decreases activity, decreases reaction, decreases uptake	1
Lisdexamfetamine Dimesylate	decreases reaction, increases transport	1
Rosiglitazone	decreases reaction, increases activity, increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Fluvastatin	decreases activity	1
Valganciclovir	increases transport, decreases reaction	1
Quinapril	decreases reaction, increases uptake	1
Ceftibuten	decreases activity, decreases uptake	1

ChEMBL screening assays

165 unique, capped per target: 89 functional, 52 admet, 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1066196	Binding	Inhibition of human PEPT1-mediated [3H]Gly-Sar uptake in human HeLa cells	Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach. — J Med Chem
CHEMBL1743153	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, PEPT1	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL2075132	Functional	TP_TRANSPORTER: inhibition of VACV uptake (VAVC: 20 uM, Ala-Ala: 10000 uM) in PEPT1-expressing CHO cells	Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line. — J Pharmacol Exp Ther

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4RS	HuH7-SLC15A1-KO-c2	Cancer cell line	Male
CVCL_D4RT	HuH7-SLC15A1-KO-c6	Cancer cell line	Male
CVCL_E0NJ	Ubigene HeLa SLC15A1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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