SLC28A2

Summary

SLC28A2 (solute carrier family 28 member 2, HGNC:11002) is a protein-coding gene on chromosome 15q21.1, encoding Sodium/nucleoside cotransporter 2 (O43868). Sodium-dependent and purine-selective transporter.

Enables neurotransmitter transmembrane transporter activity and nucleoside transmembrane transporter activity. Involved in neurotransmitter transport; nucleoside transport; and purine nucleobase transmembrane transport. Located in apicolateral plasma membrane.

Source: NCBI Gene 9153 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 102 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004212

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11002
Approved symbol	SLC28A2
Name	solute carrier family 28 member 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	CNT2, SPNT1, HCNT2, HsT17153
Ensembl gene	ENSG00000137860
Ensembl biotype	protein_coding
OMIM	606208
Entrez	9153

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000347644, ENST00000559924, ENST00000560438, ENST00000560767, ENST00000959719, ENST00000959720

RefSeq mRNA: 1 — MANE Select: NM_004212 NM_004212

CCDS: CCDS10121

Canonical transcript exons

ENST00000347644 — 18 exons

Exon	Start	End
ENSE00000685998	45272673	45272784
ENSE00000686037	45272295	45272393
ENSE00000686066	45269338	45269535
ENSE00000686071	45268210	45268378
ENSE00000686075	45267666	45267796
ENSE00000686082	45266081	45266161
ENSE00000686094	45263881	45264022
ENSE00000686098	45263061	45263244
ENSE00000686102	45262015	45262106
ENSE00000686106	45253432	45253520
ENSE00000686134	45253200	45253296
ENSE00001398081	45275396	45277846
ENSE00001673907	45270195	45270276
ENSE00002570682	45252234	45252278
ENSE00003504691	45265583	45265663
ENSE00003608318	45267455	45267580
ENSE00003619928	45265089	45265166
ENSE00003631017	45264655	45264768

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 99.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1840 / max 79.5490, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146431	0.1840	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.14	gold quality
ileal mucosa	UBERON:0000331	95.31	gold quality
duodenum	UBERON:0002114	93.18	gold quality
rectum	UBERON:0001052	91.92	gold quality
buccal mucosa cell	CL:0002336	85.72	silver quality
gall bladder	UBERON:0002110	81.60	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.12	gold quality
small intestine	UBERON:0002108	79.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.04	gold quality
colonic mucosa	UBERON:0000317	77.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.87	gold quality
jejunum	UBERON:0002115	75.51	gold quality
mucosa of transverse colon	UBERON:0004991	73.34	gold quality
pancreatic ductal cell	CL:0002079	71.64	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	70.10	gold quality
sural nerve	UBERON:0015488	69.61	gold quality
colonic epithelium	UBERON:0000397	69.38	gold quality
intestine	UBERON:0000160	65.45	gold quality
stomach	UBERON:0000945	63.78	gold quality
transverse colon	UBERON:0001157	63.02	gold quality
fundus of stomach	UBERON:0001160	62.39	gold quality
body of stomach	UBERON:0001161	62.01	gold quality
large intestine	UBERON:0000059	60.72	gold quality
colon	UBERON:0001155	60.04	gold quality
placenta	UBERON:0001987	59.32	gold quality
bronchial epithelial cell	CL:0002328	57.27	silver quality
epithelium of bronchus	UBERON:0002031	56.82	silver quality
adult mammalian kidney	UBERON:0000082	56.74	gold quality
bronchus	UBERON:0002185	56.22	silver quality
oviduct epithelium	UBERON:0004804	55.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, FOXA3, MYC

miRNA regulators (miRDB)

11 targeting SLC28A2, 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-1323	99.83	69.89	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-7855-5P	97.39	67.18	925

Literature-anchored findings (GeneRIF, showing 18)

• there are notable species differences in the specificity of SPNT for synthetic nucleoside analogs. (PMID:12110519)
• Characterization of sodium-dependent nucleoside transporter hCNT2 cloned from duodenum. (PMID:12893280)
• Human nucleoside transporters involved in cellular uptake of Bbenzamide riboside and tiazofurin and their role in cytotoxicity. (PMID:15486050)
• analysis of polymorphisms in the human concentrative nucleoside transporter, CNT2 (PMID:15861032)
• Results identify the critical domains and amino acid residues that contribute to the observed difference in specificity between concentrative nucleoside transporter (CNT)2 orthologs. (PMID:16840788)
• HNF4alpha is a major determinant of SLC28A1 expression, whereas C/EBPalpha and HNF3gamma modulate SLC28A2 gene expression. (PMID:17187757)
• hCNT2 shares common cation specificity and coupling characteristics with hCNT1, which differ markedly from those of hCNT3. (PMID:17453413)
• This study shows that adenosine elimination on human airway epithelia is mediated by ADA1, CNT2, and CNT3, which constitute important regulators of adenosine-mediated inflammation. (PMID:17696452)
• Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) expressed in U-251 cells revealed that all except E385K can uptake various substrates of CNT2: inosine, ribavirin and uridine. (PMID:17700367)
• These data suggest that selected genes of the SLC28 and SLC29 families are not only targets of HIV-1 infection, but might also contribute to the development of adipose tissue alterations leading to lipodystrophy. (PMID:17926640)
• Report expression and hepatobiliary transport characteristics of CNT2 in sandwich-cultured human hepatocytes. (PMID:18635603)
• Single nucleotide polymorphisms of this protein may play a role in variation in the pharmacokinetics and pharmacological effects of nucleoside analogs. (PMID:19098160)
• These findings support the theory that CNT2 plays roles other than salvage and establishes links with energy metabolism. (PMID:20506327)
• genetic association studies in population in Italy: Data suggest that 3 SNPs (SLC28A2 rs11854484; IL28B, rs8099917; CYP27B1, rs4646536) are associated with pharmacokinetics of ribavirin and thus, sustained virologic response in hepatitis C patients. (PMID:23149444)
• association between ribavirin (RBV) serum levels and SLC28A2 rs11854484 genotype, as well as the replicated association of ITPA and SLC28A3 genetic polymorphisms with RBV-induced anemia and treatment response (PMID:23195617)
• results that validate the newly developed structural homology model of CNT membrane architecture for human CNTs, revealed extended conformationally mobile regions within transport-domain TMs, identified pore-lining residues of functional importance, and provided evidence of an emerging novel elevator-type mechanism of transporter function. (PMID:28385889)
• significant association of intron variants in the SLC28A2 gene with both serum uric acid level and hyperuricemia phenotype, and another exonic variant with gout in Han Chinese (PMID:30679935)
• Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters. (PMID:33910126)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc28a1	ENSDARG00000060879
mus_musculus	Slc28a2	ENSMUSG00000027219
mus_musculus	Slc28a2b	ENSMUSG00000079071
rattus_norvegicus	Slc28a2	ENSRNOG00000028668
rattus_norvegicus	LOC120101643	ENSRNOG00000066870
rattus_norvegicus	LOC120101644	ENSRNOG00000068036
drosophila_melanogaster	CNT2	FBGN0025709
drosophila_melanogaster	CNT1	FBGN0033371
caenorhabditis_elegans		WBGENE00017867
caenorhabditis_elegans		WBGENE00017868

Paralogs (2): SLC28A1 (ENSG00000156222), SLC28A3 (ENSG00000197506)

Protein

Protein identifiers

Sodium/nucleoside cotransporter 2 — O43868 (reviewed: O43868)

Alternative names: Concentrative nucleoside transporter 2, Na(+)/nucleoside cotransporter 2, Sodium-coupled nucleoside transporter 2, Sodium/purine nucleoside co-transporter, Solute carrier family 28 member 2

All UniProt accessions (3): O43868, H0YNK4, H0YNM6

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-dependent and purine-selective transporter. Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine). Plays a critical role in specific uptake and salvage of purine nucleosides in kidney and other tissues. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier.

Subcellular location. Membrane. Apicolateral cell membrane.

Tissue specificity. Expressed in heart and skeletal muscle followed by liver, kidney, intestine, pancreas, placenta and brain. Weak expression in lung. In testis, primarily localized to the apicolateral membranes of Sertoli cells and vascular endothelial cells, and weakly expressed in Leydig cells, peritubular myoid cells and germ cells.

Activity regulation. Inhibited by formycin B.

Similarity. Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.

RefSeq proteins (1): NP_004203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002668	CNT_N_dom	Domain
IPR008276	C_nuclsd_transpt	Family
IPR011642	Gate_dom	Domain
IPR011657	CNT_C_dom	Domain
IPR018270	C_nuclsd_transpt_met_bac	Family

Pfam: PF01773, PF07662, PF07670

Catalyzed reactions (Rhea), 4 shown:

• uridine(out) + Na(+)(out) = uridine(in) + Na(+)(in) (RHEA:69887)
• adenosine(out) + Na(+)(out) = adenosine(in) + Na(+)(in) (RHEA:69927)
• inosine(out) + Na(+)(out) = inosine(in) + Na(+)(in) (RHEA:69931)
• guanosine(out) + Na(+)(out) = guanosine(in) + Na(+)(in) (RHEA:69935)

UniProt features (31 total): transmembrane region 14, sequence variant 12, compositionally biased region 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43868-F1	82.05	0.46

Functional residue map

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

Post-translational modifications (1): 45

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-9748787	Azathioprine ADME
R-HSA-9755088	Ribavirin ADME
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-9748784	Drug ADME

MSigDB gene sets: 214 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, BOYLAN_MULTIPLE_MYELOMA_D_DN, GOCC_COATED_VESICLE, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOCC_APICOLATERAL_PLASMA_MEMBRANE, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORT, GOBP_RETINA_HOMEOSTASIS, GOBP_NUCLEOSIDE_TRANSPORT, VECCHI_GASTRIC_CANCER_EARLY_DN, DANG_BOUND_BY_MYC

GO Biological Process (15): retina homeostasis (GO:0001895), nucleobase-containing compound metabolic process (GO:0006139), xenobiotic metabolic process (GO:0006805), neurotransmitter transport (GO:0006836), xenobiotic transmembrane transport (GO:0006855), purine nucleoside transmembrane transport (GO:0015860), uridine transmembrane transport (GO:0015862), adenosine transport (GO:0032238), inosine transport (GO:0035340), azole transmembrane transport (GO:0045117), pyrimidine-containing compound transmembrane transport (GO:0072531), transport across blood-brain barrier (GO:0150104), nucleoside transmembrane transport (GO:1901642), purine nucleobase transmembrane transport (GO:1904823), pyrimidine nucleobase transport (GO:0015855)

GO Molecular Function (8): neurotransmitter transmembrane transporter activity (GO:0005326), purine nucleobase transmembrane transporter activity (GO:0005345), nucleoside:sodium symporter activity (GO:0005415), purine nucleoside transmembrane transporter activity (GO:0015211), uridine transmembrane transporter activity (GO:0015213), pyrimidine- and adenosine-specific:sodium symporter activity (GO:0015389), azole transmembrane transporter activity (GO:1901474), nucleoside transmembrane transporter activity (GO:0005337)

GO Cellular Component (6): plasma membrane (GO:0005886), vesicle membrane (GO:0012506), membrane (GO:0016020), apicolateral plasma membrane (GO:0016327), coated vesicle (GO:0030135), brush border membrane (GO:0031526)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Drug ADME	2
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	4
nucleoside transmembrane transport	3
nucleoside transport	3
purine-containing compound transmembrane transport	2
nitrogen compound transport	2
transmembrane transporter activity	2
nucleoside transmembrane transporter activity	2
tissue homeostasis	1
primary metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
transport	1
xenobiotic transport	1
pyrimidine nucleoside transport	1
pyrimidine-containing compound transmembrane transport	1
vascular transport	1
purine nucleobase transport	1
nucleobase transport	1
neurotransmitter transport	1
nucleobase transmembrane transporter activity	1
purine nucleobase transmembrane transport	1
solute:sodium symporter activity	1
purine nucleoside transmembrane transport	1
pyrimidine nucleoside transmembrane transporter activity	1
uridine transmembrane transport	1
purine nucleobase transmembrane transporter activity	1
pyrimidine nucleobase transmembrane transporter activity	1
nucleoside:sodium symporter activity	1
nucleobase:monoatomic cation symporter activity	1
azole transmembrane transport	1
nucleobase-containing compound transmembrane transporter activity	1
carbohydrate derivative transmembrane transporter activity	1
membrane	1
cell periphery	1
organelle membrane	1
vesicle	1
cellular anatomical structure	1
plasma membrane region	1
cytoplasmic vesicle	1
brush border	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC28A2	SLC29A2	Q14542	892
SLC28A2	SLC29A1	Q99808	883
SLC28A2	SLC22A1	O15245	815
SLC28A2	SLC30A4	O14863	789
SLC28A2	GATM	P50440	773
SLC28A2	DUOX1	Q9NRD9	764
SLC28A2	SLC29A3	Q9BZD2	747
SLC28A2	DUOX2	Q9NRD8	721
SLC28A2	SLC29A4	Q7RTT9	700
SLC28A2	ADK	P55263	516
SLC28A2	SLC15A1	P46059	508
SLC28A2	SLC22A4	Q9H015	505
SLC28A2	SLC22A5	O76082	492
SLC28A2	DCK	P27707	476
SLC28A2	SLC22A7	Q9Y694	460

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SLC28A2	EMC8	psi-mi:“MI:0914”(association)	0.350
SLC28A2	NACA	psi-mi:“MI:0914”(association)	0.350
SLCO2B1	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): ALG8 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), TUSC3 (Affinity Capture-MS), C16orf71 (Affinity Capture-MS), SARAF (Affinity Capture-MS), RNF181 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), EMC8 (Affinity Capture-MS), SPCS1 (Affinity Capture-MS), EMC2 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), EMC4 (Affinity Capture-MS), ALG12 (Affinity Capture-MS), KIAA0368 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KQY6, A0A6I8PMZ8, A0JPN2, A4IGY6, A5D7L5, A7T1N0, B3DHU2, O43868, O75899, O88871, O94402, P04919, P0DX17, P23562, P26432, P26433, P48764, P55205, Q08E40, Q0DHJ5, Q0DWA9, Q0VCH8, Q15043, Q28C60, Q4VAE3, Q504Y0, Q5FVQ0, Q5FWH7, Q5RAB7, Q5Z413, Q6DCK1, Q6L8F3, Q6PI78, Q75N73, Q78IQ7, Q80T41, Q8K596, Q8VIH3, Q8W469, Q91W10

Diamond homologs: E9PXX9, O00337, O25792, O32115, O43868, O62667, O88627, P33021, P33024, P44742, Q62674, Q62773, Q8VIH3, Q9ERH8, Q9HAS3, Q9MZT2, Q9UA35, P39141, P0AFF2, P0AFF3, P42312

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2512 predictions. Top by Δscore:

Variant	Effect	Δscore
15:45252276:GGG:G	donor_gain	1.0000
15:45252277:GG:G	donor_gain	1.0000
15:45252277:GGG:G	donor_gain	1.0000
15:45252278:GG:G	donor_gain	1.0000
15:45252278:GGTA:G	donor_loss	1.0000
15:45252279:G:GA	donor_loss	1.0000
15:45262131:G:GG	donor_gain	1.0000
15:45263058:TA:T	acceptor_loss	1.0000
15:45263059:A:AG	acceptor_gain	1.0000
15:45263059:AGCCT:A	acceptor_loss	1.0000
15:45263060:G:GA	acceptor_gain	1.0000
15:45263060:GC:G	acceptor_gain	1.0000
15:45263060:GCC:G	acceptor_gain	1.0000
15:45263060:GCCT:G	acceptor_gain	1.0000
15:45263060:GCCTA:G	acceptor_gain	1.0000
15:45263242:ATGGT:A	donor_loss	1.0000
15:45263243:TGGT:T	donor_loss	1.0000
15:45263245:G:GA	donor_loss	1.0000
15:45263245:G:GG	donor_gain	1.0000
15:45263250:A:G	donor_gain	1.0000
15:45265084:TTCA:T	acceptor_loss	1.0000
15:45265086:CAG:C	acceptor_loss	1.0000
15:45265087:A:AG	acceptor_gain	1.0000
15:45265088:G:GA	acceptor_gain	1.0000
15:45265088:G:T	acceptor_loss	1.0000
15:45265088:GATT:G	acceptor_gain	1.0000
15:45265144:TC:T	donor_gain	1.0000
15:45265149:G:GT	donor_gain	1.0000
15:45265659:AGAAG:A	donor_loss	1.0000
15:45265663:GGT:G	donor_loss	1.0000

AlphaMissense

4291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:45270234:T:C	F536L	0.986
15:45270236:T:A	F536L	0.986
15:45270236:T:G	F536L	0.986
15:45270219:T:C	F531L	0.975
15:45270221:T:A	F531L	0.975
15:45270221:T:G	F531L	0.975
15:45265126:T:A	V247D	0.974
15:45268232:G:C	A408P	0.974
15:45268236:C:A	A409D	0.970
15:45269453:C:A	A495D	0.963
15:45269485:C:A	R506S	0.962
15:45269410:G:C	A481P	0.961
15:45268238:A:C	S410R	0.959
15:45268240:C:A	S410R	0.959
15:45268240:C:G	S410R	0.959
15:45269411:C:A	A481D	0.959
15:45272378:A:C	S578R	0.958
15:45272380:T:A	S578R	0.958
15:45272380:T:G	S578R	0.958
15:45270246:A:C	S540R	0.957
15:45270248:T:A	S540R	0.957
15:45270248:T:G	S540R	0.957
15:45265096:T:C	L237P	0.956
15:45269486:G:C	R506P	0.956
15:45270242:T:A	N538K	0.956
15:45270242:T:G	N538K	0.956
15:45272357:G:T	G571W	0.954
15:45268290:T:C	L427P	0.953
15:45268235:G:C	A409P	0.952
15:45268305:C:A	A432D	0.952

dbSNP variants (sampled 300 via entrez): RS1000027020 (15:45277095 C>T), RS1000058390 (15:45276743 T>C), RS1000224601 (15:45262416 G>C), RS1000225543 (15:45259410 A>G), RS1000266068 (15:45256094 T>C), RS1000328976 (15:45263217 A>G,T), RS1000581802 (15:45260407 C>T), RS1000645898 (15:45255292 T>C), RS1000722312 (15:45255768 G>A), RS1000872501 (15:45272907 C>T), RS1001056421 (15:45275272 T>C), RS1001151049 (15:45266895 G>C), RS1001316818 (15:45270933 G>C), RS1001389536 (15:45268032 T>A), RS1001560320 (15:45271393 T>A)

Disease associations

OMIM: gene MIM:606208 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001374_4	Uric acid levels	3.000000e-06
GCST007876_8	Estimated glomerular filtration rate	1.000000e-56
GCST009733_115	Urinary metabolite levels in chronic kidney disease	8.000000e-25
GCST009733_28	Urinary metabolite levels in chronic kidney disease	1.000000e-26

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5780 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 325,018 (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
CHEMBL477	ADENOSINE	4	222,014
CHEMBL100259	URIDINE	3	103,004

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1060896	Efficacy,Toxicity	3	gemcitabine	Neoplasms
rs11854484	Toxicity	3	peginterferon alfa-2b;protease inhibitors;ribavirin	Hepatitis C virus infection
rs11854484	Toxicity	3	tenofovir disoproxil fumarate	HIV infectious disease;Nephrotoxicity
rs11854484	Efficacy	3	gemcitabine	Non-Small Cell Lung Carcinoma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1060896	SLC28A2	3	2.50	1	gemcitabine
rs2413775	SLC28A2		0.00	0
rs11854484	SLC28A2	3	2.75	3	tenofovir disoproxil fumarate;gemcitabine;peginterferon alfa-2b;protease inhibitors;ribavirin

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC28 family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 48 [PMID: 25815140]	Inhibition	6.19	pIC50

ChEMBL bioactivities

30 potent at pChembl≥5 of 43 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	IC50	62	nM	CHEMBL3808747
6.19	IC50	640	nM	CHEMBL3427690
6.03	IC50	940	nM	CHEMBL3809613
6.00	IC50	1000	nM	CHEMBL3809974
5.96	IC50	1100	nM	CHEMBL3809514
5.96	IC50	1100	nM	CHEMBL3809075
5.92	IC50	1200	nM	CHEMBL3808410
5.89	IC50	1300	nM	CHEMBL3809204
5.89	IC50	1300	nM	CHEMBL3809978
5.82	IC50	1500	nM	CHEMBL3809948
5.80	IC50	1600	nM	CHEMBL3809286
5.79	IC50	1610	nM	THPP-1
5.64	IC50	2300	nM	CHEMBL3810002
5.57	IC50	2700	nM	CHEMBL3808652
5.51	IC50	3100	nM	CHEMBL3808498
5.48	IC50	3300	nM	CHEMBL3808970
5.28	IC50	5300	nM	CHEMBL3427687
5.28	Ki	5300	nM	ADENOSINE
5.28	IC50	5200	nM	CHEMBL3808769
5.27	IC50	5400	nM	CHEMBL3427681
5.27	IC50	5400	nM	CHEMBL3808969
5.26	IC50	5500	nM	ADENOSINE
5.26	IC50	5500	nM	CHEMBL3808734
5.24	IC50	5700	nM	CHEMBL3427686
5.24	IC50	5700	nM	CHEMBL3427680
5.03	IC50	9300	nM	CHEMBL3808405
5.01	IC50	9700	nM	MLi-2
5.00	IC50	1e+04	nM	CHEMBL5270911

PubChem BioAssay actives

27 with measured affinity, of 88 total; 25 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
(2R,3R,4S,5R)-2-[2-[[3-(4-hydroxybutoxy)-4-phenylphenyl]methylamino]benzimidazol-1-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	0.0620	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1205658: Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	ic50	0.6400	uM
(2R,3R,4S,5R)-2-[6-amino-8-[[3-(4-hydroxybutoxy)-4-phenylphenyl]methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	0.9400	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-pyridin-3-ylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.0000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(2-methoxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.1000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[[3-(3-hydroxypropoxy)-4-phenylphenyl]methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.1000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3-hydroxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.2000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(2-hydroxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3-methoxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-pyridin-2-ylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.5000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[[3-(5-hydroxypentoxy)-4-phenylphenyl]methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	1.6000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3-ethoxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	2.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-pyridin-4-ylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	2.7000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[[3-(2-hydroxyethoxy)-4-phenylphenyl]methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	3.1000	uM
methyl 2-[5-[[[6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-8-yl]amino]methyl]-2-phenylphenoxy]acetate	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	3.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-phenyl-3-propoxyphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	5.2000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(naphthalen-2-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1205658: Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	ic50	5.3000	uM
Adenosine	1222908: Binding affinity to recombinant human CNT2 expressed in Saccharomyces cerevisiae assessed as inhibition of [3H]-uridine transport after 15 mins by scintillation counting analysis	ki	5.3000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(3-chlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1205658: Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	ic50	5.4000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(2-ethoxy-4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	5.4000	uM
2-[5-[[[6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-8-yl]amino]methyl]-2-phenylphenoxy]acetamide	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	5.5000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(2-chlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1205658: Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	ic50	5.7000	uM
(2R,3R,4S,5R)-2-[6-amino-8-(naphthalen-1-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1205658: Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	ic50	5.7000	uM
(2R,3R,4S,5R)-2-[6-amino-8-[(4-phenyl-2-propan-2-yloxyphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	1301687: Inhibition of human CNT2 expressed in African green monkey COS7 cells assessed as reduction of [14C]-inosine uptake by liquid scintillation counting analysis	ic50	9.3000	uM
(1S,2S,4S,5S)-4-(6-aminopurin-9-yl)-1-(hydroxymethyl)bicyclo[3.1.0]hexan-2-ol	1930054: Inhibition of human CNT2	ic50	10.0000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	2
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Adenosine	increases transport	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Deoxyadenosines	increases transport	1
Plant Extracts	affects cotreatment, decreases expression	1
Purine Nucleosides	increases transport	1
Sodium	increases transport	1
Uridine	increases transport	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

17 unique, capped per target: 15 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3428943	Binding	Inhibition of human CNT2 expressed in COS7 cells assessed as reduction in sodium-dependent [14C]-inosine uptake in presence of Na+ by liquid scintillation counting method	Identification of 8-aminoadenosine derivatives as a new class of human concentrative nucleoside transporter 2 inhibitors. — ACS Med Chem Lett
CHEMBL3528993	ADMET	Binding affinity to recombinant human CNT2 expressed in Saccharomyces cerevisiae assessed as inhibition of [3H]-uridine transport after 15 mins by scintillation counting analysis	Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1. — Drug Metab Dispos

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4VK	LS180-SLC28A2-KO-c1	Cancer cell line	Female
CVCL_D4VL	LS180-SLC28A2-KO-c3	Cancer cell line	Female

Clinical trials (associated diseases)

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