SLC29A2

Summary

SLC29A2 (solute carrier family 29 member 2, HGNC:11004) is a protein-coding gene on chromosome 11q13.2, encoding Equilibrative nucleoside transporter 2 (Q14542). Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis.

The uptake of nucleosides by transporters, such as SLC29A2, is essential for nucleotide synthesis by salvage pathways in cells that lack de novo biosynthetic pathways. Nucleoside transport also plays a key role in the regulation of many physiologic processes through its effect on adenosine concentration at the cell surface (Griffiths et al., 1997 [PubMed 9396714]).

Source: NCBI Gene 3177 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_001532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11004
Approved symbol	SLC29A2
Name	solute carrier family 29 member 2
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DER12
Ensembl gene	ENSG00000174669
Ensembl biotype	protein_coding
OMIM	602110
Entrez	3177

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 2 nonsense_mediated_decay

ENST00000311161, ENST00000357440, ENST00000540386, ENST00000541567, ENST00000544554, ENST00000546034, ENST00000619145, ENST00000873641, ENST00000932622, ENST00000932623, ENST00000932624, ENST00000932625, ENST00000932626, ENST00000932627, ENST00000932628, ENST00000944718, ENST00000944719

RefSeq mRNA: 3 — MANE Select: NM_001532 NM_001300868, NM_001300869, NM_001532

CCDS: CCDS73326, CCDS8137

Canonical transcript exons

ENST00000357440 — 12 exons

Exon	Start	End
ENSE00001189124	66369060	66369199
ENSE00001189128	66369369	66369532
ENSE00001189132	66371244	66371325
ENSE00003494038	66364225	66364424
ENSE00003512896	66367772	66367869
ENSE00003521504	66366126	66366231
ENSE00003549563	66366431	66366564
ENSE00003575651	66367464	66367548
ENSE00003605597	66365936	66366021
ENSE00003693328	66368537	66368671
ENSE00003846486	66362521	66363547
ENSE00003846988	66371563	66371760

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.4437 / max 352.4793, expressed in 1191 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120800	11.2793	1125
120797	2.1303	414
120798	0.9425	364
120803	0.3536	190
120801	0.2674	134
120802	0.2347	114
120799	0.1468	77
120804	0.0892	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.64	gold quality
muscle of leg	UBERON:0001383	94.39	gold quality
apex of heart	UBERON:0002098	93.66	gold quality
muscle organ	UBERON:0001630	92.82	gold quality
mucosa of transverse colon	UBERON:0004991	91.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.22	gold quality
right atrium auricular region	UBERON:0006631	89.94	gold quality
body of tongue	UBERON:0011876	89.70	gold quality
vastus lateralis	UBERON:0001379	89.58	gold quality
cerebellar hemisphere	UBERON:0002245	89.18	gold quality
quadriceps femoris	UBERON:0001377	89.09	gold quality
cerebellar cortex	UBERON:0002129	88.90	gold quality
skeletal muscle tissue	UBERON:0001134	88.68	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.65	gold quality
cardiac atrium	UBERON:0002081	88.51	gold quality
heart left ventricle	UBERON:0002084	86.76	gold quality
metanephros cortex	UBERON:0010533	86.74	gold quality
cerebellum	UBERON:0002037	86.31	gold quality
biceps brachii	UBERON:0001507	86.17	gold quality
cardiac ventricle	UBERON:0002082	86.09	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.62	gold quality
muscle tissue	UBERON:0002385	85.47	gold quality
endometrium epithelium	UBERON:0004811	85.24	silver quality
body of stomach	UBERON:0001161	84.61	gold quality
body of pancreas	UBERON:0001150	84.48	gold quality
heart	UBERON:0000948	83.94	gold quality
triceps brachii	UBERON:0001509	83.78	gold quality
transverse colon	UBERON:0001157	83.48	gold quality
diaphragm	UBERON:0001103	83.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

34 targeting SLC29A2, 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-4481	100.00	66.42	1669
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-6736-3P	96.98	65.22	1342

Literature-anchored findings (GeneRIF, showing 28)

• role in functional and molecular characterization of nucleobase transport (PMID:12006583)
• hENT1 and hENT2 on the basolateral membrane function with concentrative nucleoside transporters on the apical membrane to mediate active reabsorption of nucleosides within the kidney. (PMID:12527552)
• an analysis of function by site-directed glycosylation mutagenesis (PMID:12590919)
• Equilibrative nucleoside transporters (hENT1, hENT2) together with adenosine kinase and 5’-nucleotidase play a crucial role in the regulation of CFTR through an adenosine-dependent pathway in human airway epithelia. (PMID:12820662)
• Only a few endometrial carcinomas (15%) were found to be negative for hCNT1, but they all retained hENT1 and hENT2 expression. (PMID:15386342)
• residue 33 resides in an extracellular domain as predicted by the current hENT2 topology model and suggested that it is a functionally important component of both the permeant and dipyridamole binding sites. (PMID:15644498)
• the corresponding residues in TMs 1 and 11 of hENT1, hENT2, and CeENT1 are important for dipyridamole interactions and nucleoside transport. (PMID:15649894)
• The low overall genetic diversity in SLC29A2 makes it unlikely that variation in the coding region contributes significantly to clinically observed differences in drug response. (PMID:16214850)
• Data show that insulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium. (PMID:16924660)
• Human cardiac microvascular endothelial cells rely on ENT1 for nucleoside transport with little contribution from ENT2. (PMID:17921321)
• 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 ENT2 in sandwich-cultured human hepatocytes. (PMID:18635603)
• hPMEC from pre-eclampsia exhibit increased total transport (hENT1+hENT2), and maximal velocity (Vmax) for hENT2- (2-fold), but reduced Vmax for hENT1-mediated adenosine transport (PMID:18703227)
• correlation between the recently described p53-inducible apoptosis gene TIGAR and both sensitivity to fludarabine and hENT2 expression in chronic lymphocytic leukemia cells. (PMID:18945750)
• HIF-1alpha-dependent repression of ENT2 increases mucosal adenosine signaling and attenuates hypoxia-associated inflammation of the intestine. (PMID:19105964)
• This evidence suggested that apical CNT3 and basolateral ENT2 are involved in proximal tubular reabsorption of adenosine and some nucleoside drugs and that apical ENT1 is involved in proximal tubular secretion of 2’-deoxyadenosine. (PMID:19297449)
• Studies show that ABCC4 and SLC29A2 expression were predictive of achieving CR, and the high expression of GSTP1 suggests that this may be a therapeutic target for relapsed AML. (PMID:21156465)
• Data show that ENT1, ENT2, ENT4 and CNT3 protein was detected on ovarian carcinoma cells in all effusions, with expression observed in 1-95% of tumor cells. (PMID:21822668)
• these findings reveal the transcriptional repression of ENT1,2 as an innate protective response during acute pulmonary inflammation. (PMID:23590299)
• Data suggest that SLC29A2 is localized to apical membrane of adult Sertoli cells. In contrast, SLC29A1 is located on basolateral membrane of Sertoli cells; SLC29A1 is primarily responsible for basolateral nucleoside uptake into Sertoli cells. (PMID:23639800)
• Direct evidence for apical localization of ENT1 and integral expression of ENT2 in intestinal epithelial cells. (PMID:27160886)
• two novel functional splice variants of equilibrative nucleoside transporter 2 (ENT2), which are present at the nuclear envelope, were identified. (PMID:27271752)
• Results showed that both SLC29A1 and SLC29A2 were expressed at lower levels in colon cancer cell lines originating from metastatic sites than from primary sites. (PMID:28218790)
• Hypoxia did not change expression of either hENT1, hENT2, or TK1. (PMID:31601121)
• Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma. (PMID:33994542)
• Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites. (PMID:34503974)
• Deletion of equilibrative nucleoside transporter 2 disturbs energy metabolism and exacerbates disease progression in an experimental model of Huntington’s disease. (PMID:36669543)
• Functional nucleoside transporter in stable and transient transfection studies in mammalian cells. (PMID:9478986)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc29a2	ENSDARG00000001767
danio_rerio		ENSDARG00000099078
mus_musculus	Slc29a2	ENSMUSG00000024891
rattus_norvegicus	Slc29a2	ENSRNOG00000020025
drosophila_melanogaster	Ent1	FBGN0031250

Paralogs (3): SLC29A1 (ENSG00000112759), SLC29A4 (ENSG00000164638), SLC29A3 (ENSG00000198246)

Protein

Protein identifiers

Equilibrative nucleoside transporter 2 — Q14542 (reviewed: Q14542)

Alternative names: 36 kDa nucleolar protein HNP36, Delayed-early response protein 12, Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter, Hydrophobic nucleolar protein, 36 kDa, Nucleoside transporter, ei-type, Solute carrier family 29 member 2

All UniProt accessions (1): Q14542

UniProt curated annotations — full annotation on UniProt →

Function. Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis. Functions as a Na(+)-independent, passive transporter. Involved in the transport of nucleosides such as inosine, adenosine, uridine, thymidine, cytidine and guanosine. Also able to transport purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil). Involved in nucleoside transport at basolateral membrane of kidney cells, allowing liver absorption of nucleoside metabolites. Mediates apical nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis-barrier. Mediates both the influx and efflux of hypoxanthine in skeletal muscle microvascular endothelial cells to control the amount of intracellular hypoxanthine available for xanthine oxidase-mediated ROS production. Non functional nucleoside transporter protein for adenosine or thymidine transport. Does not express on cell membrane.

Subcellular location. Apical cell membrane. Basolateral cell membrane.

Tissue specificity. Highly expressed in skeletal muscle. Expressed in liver, lung, placenta, brain, heart, kidney and ovarian tissues. Expressed in testis at the blood-brain-barrier.

Post-translational modifications. Glycosylated.

Miscellaneous. Transport activity is insensitive to nanomolar concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR). Inhibited by higher concentrations of NBMPR (1uM-10uM). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14542-1	1, Long	yes
Q14542-2	2, Short, HNP36
Q14542-3	3, hENT2A
Q14542-4	4

RefSeq proteins (3): NP_001287797, NP_001287798, NP_001523* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002259	Eqnu_transpt	Family
IPR034764	ENT1/ENT2	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF01733

Catalyzed reactions (Rhea), 11 shown:

• uracil(in) = uracil(out) (RHEA:69404)
• hypoxanthine(out) = hypoxanthine(in) (RHEA:71515)
• uridine(out) = uridine(in) (RHEA:71519)
• adenine(out) = adenine(in) (RHEA:71523)
• thymine(out) = thymine(in) (RHEA:71527)
• guanine(out) = guanine(in) (RHEA:71531)
• adenosine(in) = adenosine(out) (RHEA:75343)
• thymidine(in) = thymidine(out) (RHEA:75363)
• cytidine(in) = cytidine(out) (RHEA:75367)
• guanosine(in) = guanosine(out) (RHEA:75371)
• inosine(in) = inosine(out) (RHEA:75375)

UniProt features (30 total): transmembrane region 11, splice variant 5, sequence variant 4, mutagenesis site 4, glycosylation site 3, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14542-F1	84.48	0.61

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): 252

Glycosylation sites (3): 48, 57, 225

Mutagenesis-validated functional residues (4):

Position	Phenotype
48	no difference in uridine or cytidine uptake. no differences in km values and lower vmax values for either uridine or cyt
57	no difference in uridine or cytidine uptake. no differences in km values and lower vmax values for either uridine or cyt
455	reduces drastically localization at the cell surface. no effect on uptake of adenosine and thymidine. reduces drasticall
456	reduces drastically localization at the cell surface and induces an significant reduction of adenosine or thymidine upta

Function

Pathways and Gene Ontology

Reactome pathways

6 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-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: 160 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, chr11q13, SHEPARD_BMYB_MORPHOLINO_DN, GCM_RING1, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (20): neurotransmitter uptake (GO:0001504), neurotransmitter transport (GO:0006836), xenobiotic transmembrane transport (GO:0006855), nucleobase transport (GO:0015851), adenine transport (GO:0015853), guanine transport (GO:0015854), nucleoside transport (GO:0015858), purine nucleoside transmembrane transport (GO:0015860), cytidine transport (GO:0015861), uridine transmembrane transport (GO:0015862), adenosine transport (GO:0032238), inosine transport (GO:0035340), hypoxanthine transport (GO:0035344), thymine transport (GO:0035364), pyrimidine-containing compound transmembrane transport (GO:0072531), transport across blood-brain barrier (GO:0150104), nucleoside transmembrane transport (GO:1901642), guanine transmembrane transport (GO:1903716), uracil transmembrane transport (GO:1903791), purine nucleobase transmembrane transport (GO:1904823)

GO Molecular Function (9): neurotransmitter transmembrane transporter activity (GO:0005326), nucleoside transmembrane transporter activity (GO:0005337), nucleobase transmembrane transporter activity (GO:0015205), adenine transmembrane transporter activity (GO:0015207), guanine transmembrane transporter activity (GO:0015208), uracil transmembrane transporter activity (GO:0015210), purine nucleoside transmembrane transporter activity (GO:0015211), cytidine transmembrane transporter activity (GO:0015212), uridine transmembrane transporter activity (GO:0015213)

GO Cellular Component (5): nucleolus (GO:0005730), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine nucleobase transport	4
transmembrane transport	3
nucleoside transmembrane transport	3
nucleoside transport	3
neurotransmitter transport	2
nitrogen compound transport	2
purine-containing compound transmembrane transport	2
pyrimidine nucleoside transport	2
transmembrane transporter activity	2
purine nucleobase transmembrane transporter activity	2
pyrimidine nucleoside transmembrane transporter activity	2
plasma membrane region	2
import into cell	1
transport	1
xenobiotic transport	1
nucleobase-containing compound transport	1
carbohydrate derivative transport	1
pyrimidine-containing compound transmembrane transport	1
pyrimidine nucleobase transport	1
vascular transport	1
guanine transport	1
purine nucleobase transmembrane transport	1
uracil transport	1
pyrimidine nucleobase transmembrane transport	1
nucleobase-containing compound transmembrane transporter activity	1
carbohydrate derivative transmembrane transporter activity	1
nucleobase transport	1
adenine transport	1
guanine transmembrane transport	1
pyrimidine nucleobase transmembrane transporter activity	1
uracil transmembrane transport	1
nucleoside transmembrane transporter activity	1
purine nucleoside transmembrane transport	1
cytidine transport	1
uridine transmembrane transport	1
nuclear lumen	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
basal plasma membrane	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC29A2	SLC28A1	O00337	893
SLC29A2	SLC28A2	O43868	892
SLC29A2	SLC28A3	Q9HAS3	892
SLC29A2	ADORA1	P30542	689
SLC29A2	ADK	P55263	684
SLC29A2	CD63	P08962	649
SLC29A2	DCK	P27707	633
SLC29A2	ADA	P00813	593
SLC29A2	SLC22A4	Q9H015	572
SLC29A2	SLC22A5	O76082	569
SLC29A2	SLC22A7	Q9Y694	512
SLC29A2	ABCC4	O15439	490
SLC29A2	SLCO3A1	Q9UIG8	488
SLC29A2	NT5E	P21589	468
SLC29A2	ADORA2A	P29274	464

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CREB3	SLC29A2	psi-mi:“MI:0915”(physical association)	0.370
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
SLC22A9	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC29A2	EIF3CL	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): UBQLN1 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Proximity Label-MS), SLC29A2 (Proximity Label-MS), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid), SLC29A2 (Two-hybrid)

ESM2 similar proteins: A1A4N1, A2AWR3, A2VE54, B0S5Y3, B2RXV4, B5X4H8, C1BKZ7, D2HSA6, O00400, O54698, O54699, O75387, P28573, Q08B29, Q0VCM6, Q14542, Q28E13, Q4FZU9, Q4HX89, Q5E9R1, Q5RF58, Q60825, Q61672, Q62687, Q6AYY8, Q6BZ39, Q6BZW3, Q6GMG6, Q6PGE7, Q710D3, Q758C3, Q80WK7, Q84XI3, Q86WB7, Q8CGA3, Q8N370, Q8VXY7, Q944P0, Q94AA1, Q99808

Diamond homologs: A1A4N1, O54698, O54699, Q14542, Q61672, Q80WK7, Q99808, Q99P65, Q9BZD2, Q9JIM1, Q9NBV4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2069 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66364306:T:TA	donor_gain	1.0000
11:66365934:A:AC	donor_gain	1.0000
11:66365934:AC:A	donor_gain	1.0000
11:66365935:C:CC	donor_gain	1.0000
11:66365935:CC:C	donor_gain	1.0000
11:66365935:CCCA:C	donor_gain	1.0000
11:66366017:CTGAC:C	acceptor_gain	1.0000
11:66366018:TGACC:T	acceptor_loss	1.0000
11:66366020:ACC:A	acceptor_loss	1.0000
11:66366021:CCTGG:C	acceptor_loss	1.0000
11:66366124:A:AC	donor_gain	1.0000
11:66366124:ACT:A	donor_gain	1.0000
11:66366124:ACTC:A	donor_gain	1.0000
11:66366125:C:CT	donor_gain	1.0000
11:66366125:CT:C	donor_gain	1.0000
11:66366125:CTC:C	donor_gain	1.0000
11:66366125:CTCC:C	donor_gain	1.0000
11:66366125:CTCCA:C	donor_gain	1.0000
11:66366132:T:TA	donor_gain	1.0000
11:66366133:C:A	donor_gain	1.0000
11:66366192:C:CC	acceptor_gain	1.0000
11:66366392:C:A	donor_gain	1.0000
11:66366565:C:CC	acceptor_gain	1.0000
11:66366570:G:GC	acceptor_gain	1.0000
11:66367458:GCTTA:G	donor_loss	1.0000
11:66367459:CTT:C	donor_loss	1.0000
11:66367460:TTA:T	donor_loss	1.0000
11:66367462:A:AC	donor_gain	1.0000
11:66367462:A:AT	donor_loss	1.0000
11:66367463:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000180735 (11:66362107 T>C,G), RS1000230951 (11:66362474 A>T), RS1000266554 (11:66370121 G>A,T), RS1000835181 (11:66372431 C>A), RS1000926450 (11:66372701 C>T), RS1001404625 (11:66370703 A>C), RS1001774164 (11:66370418 T>G), RS1002844050 (11:66369822 G>A), RS1002938667 (11:66370153 C>T), RS1003032975 (11:66371775 G>A,T), RS1003359845 (11:66362580 G>A), RS1003476130 (11:66371922 C>G,T), RS1003823041 (11:66362872 G>A), RS1003889759 (11:66372398 C>T), RS1003966322 (11:66366358 C>T)

Disease associations

OMIM: gene MIM:602110 | 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
GCST001241_12	Bipolar disorder	2.000000e-07
GCST010512_21	Serum uric acid levels	1.000000e-11
GCST012020_186	Serum metabolite levels	6.000000e-11
GCST012021_111	Serum metabolite levels	6.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3509606 (SINGLE PROTEIN), CHEMBL6066081 (PROTEIN FAMILY)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC29 family

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	IC50	570	nM	CHEMBL1325639
5.77	IC50	1690	nM	CHEMBL5219061
5.36	IC50	4360	nM	CHEMBL5219061

PubChem BioAssay actives

3 with measured affinity, of 12 total; 2 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
6-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-2-N-(3-methylphenyl)-1,3,5-triazine-2,4-diamine	1917087: Inhibition of human ENT2 transfected in nucleoside transporter-deficient pig PK-15 cells assessed as inhibition of [3H]-uridine uptake by liquid scintillation counter analysis	ic50	0.5700	uM
6-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]-2-N-naphthalen-1-yl-1,3,5-triazine-2,4-diamine	1917087: Inhibition of human ENT2 transfected in nucleoside transporter-deficient pig PK-15 cells assessed as inhibition of [3H]-uridine uptake by liquid scintillation counter analysis	ic50	1.6900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Uridine	affects cotreatment, decreases reaction, increases uptake, increases reaction	2
Valproic Acid	increases methylation, affects expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
4-nitrobenzylthioinosine	increases reaction, affects cotreatment, decreases reaction, increases uptake	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
3-iodothyronamine	affects uptake	1
trans-10,cis-12-conjugated linoleic acid	increases expression	1
abrine	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
fatostatin	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Decitabine	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Adenosine	increases uptake	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Azacitidine	decreases expression	1
Cadmium	increases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 4 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3528991	ADMET	Binding affinity to recombinant human ENT2 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
CHEMBL5216607	Binding	Inhibition of human ENT2 transfected in nucleoside transporter-deficient pig PK-15 cells assessed as inhibition of [3H]-adenosine uptake by liquid scintillation counter analysis	A closer look at N2,6-substituted 1,3,5-triazine-2,4-diamines: Advances in synthesis and biological activities. — Eur J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9RW	Ubigene HEK293 SLC29A2 KO	Transformed cell line	Female
CVCL_TM75	HAP1 SLC29A2 (-) 1	Cancer cell line	Male
CVCL_XT11	HAP1 SLC29A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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