SLC28A1

Summary

SLC28A1 (solute carrier family 28 member 1, HGNC:11001) is a protein-coding gene on chromosome 15q25.3, encoding Sodium/nucleoside cotransporter 1 (O00337). Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient.

Enables azole transmembrane transporter activity; pyrimidine- and adenosine-specific:sodium symporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport and nucleoside transport. Located in apical plasma membrane; cytosol; and nuclear speck.

Source: NCBI Gene 9154 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 131 total — 1 pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11001
Approved symbol	SLC28A1
Name	solute carrier family 28 member 1
Location	15q25.3
Locus type	gene with protein product
Status	Approved
Aliases	CNT1
Ensembl gene	ENSG00000156222
Ensembl biotype	protein_coding
OMIM	606207
Entrez	9154

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 21 protein_coding

ENST00000286749, ENST00000338602, ENST00000394573, ENST00000538177, ENST00000859183, ENST00000859184, ENST00000859185, ENST00000859186, ENST00000859187, ENST00000859188, ENST00000859189, ENST00000859190, ENST00000859191, ENST00000859192, ENST00000859193, ENST00000859194, ENST00000859195, ENST00000859196, ENST00000859197, ENST00000859198, ENST00000859199

RefSeq mRNA: 6 — MANE Select: NM_004213 NM_001287761, NM_001287762, NM_001321721, NM_001321722, NM_004213, NM_201651

CCDS: CCDS10334, CCDS10335, CCDS73777

Canonical transcript exons

ENST00000394573 — 19 exons

Exon	Start	End
ENSE00001229496	84886672	84886787
ENSE00003844455	84884662	84884751
ENSE00003845897	84945125	84945798
ENSE00003889099	84923985	84924110
ENSE00003889219	84887745	84887856
ENSE00003889499	84944756	84944867
ENSE00003889590	84944566	84944664
ENSE00003889712	84888772	84888860
ENSE00003890211	84908718	84908795
ENSE00003890220	84918524	84918604
ENSE00003890337	84894940	84895123
ENSE00003892365	84920989	84921069
ENSE00003892559	84935026	84935194
ENSE00003893322	84904097	84904238
ENSE00003893654	84890443	84890534
ENSE00003893723	84943445	84943526
ENSE00003894291	84905539	84905652
ENSE00003895584	84933145	84933275
ENSE00003895955	84935321	84935518

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 96.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4359 / max 135.5677, expressed in 26 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148154	0.2093	20
148155	0.0818	17
148157	0.0737	11
148153	0.0446	13
148158	0.0181	8
148156	0.0083	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.21	silver quality
liver	UBERON:0002107	88.56	gold quality
adult mammalian kidney	UBERON:0000082	87.30	gold quality
diaphragm	UBERON:0001103	85.63	silver quality
duodenum	UBERON:0002114	84.71	gold quality
ileal mucosa	UBERON:0000331	83.14	gold quality
kidney	UBERON:0002113	79.25	gold quality
jejunal mucosa	UBERON:0000399	78.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.36	silver quality
biceps brachii	UBERON:0001507	76.19	gold quality
metanephros cortex	UBERON:0010533	75.11	gold quality
cortex of kidney	UBERON:0001225	75.02	gold quality
small intestine	UBERON:0002108	74.63	gold quality
buccal mucosa cell	CL:0002336	73.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.64	gold quality
kidney epithelium	UBERON:0004819	72.35	silver quality
cervix squamous epithelium	UBERON:0006922	72.33	gold quality
nephron tubule	UBERON:0001231	71.68	silver quality
hindlimb stylopod muscle	UBERON:0004252	71.54	gold quality
orbitofrontal cortex	UBERON:0004167	70.27	gold quality
tongue squamous epithelium	UBERON:0006919	69.96	gold quality
cerebellar vermis	UBERON:0004720	69.77	gold quality
vastus lateralis	UBERON:0001379	68.34	gold quality
quadriceps femoris	UBERON:0001377	68.27	gold quality
jejunum	UBERON:0002115	68.22	gold quality
apex of heart	UBERON:0002098	68.08	gold quality
type B pancreatic cell	CL:0000169	67.80	gold quality
olfactory bulb	UBERON:0002264	67.50	gold quality
male germ cell	CL:0000015	67.38	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	48.95
E-ANND-3	yes	3.19
E-CURD-53	no	43.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

47 targeting SLC28A1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277

Literature-anchored findings (GeneRIF, showing 28)

• hCNT1 and hENT1 are expressed in polarized MDCK cells on the apical and basolateral membrane, respectively, allowing vectorial transport in both directions depending on the relative activity of each transporter for their substrates (PMID:12097333)
• human pancreatic adenocarcinoma cells overexpress hENT1, although they retain the ability to express a functional hCNT1 transporter, an isoform that confers sensitivity to gemcitabine (PMID:14581375)
• hCNT1 was by far the isoform whose expression was most frequently reduced or lost in the 3 types of gynecologic tumors analyzed.In uterine cervix tumors, the loss of expression of hCNT1 was significantly associated with the adenocarcinoma subtype. (PMID:15386342)
• the N4 transport system is a naturally occurring variant of hCNT1, perhaps at the F316 position. Collectively, and G476 is important for correct membrane targeting, folding, and/or intracellular processing of hCNT1 (PMID:15456697)
• HNF4alpha is a major determinant of SLC28A1 expression, whereas C/EBPalpha and HNF3gamma modulate SLC28A2 gene expression. (PMID:17187757)
• We now report the effects of mutations in transmembrane helix 8 & demonstrate unique S353T- and L354V-induced changes in nucleoside specificity and cation coupling, respectively. (PMID:17279631)
• hCNT2 shares common cation specificity and coupling characteristics with hCNT1, which differ markedly from those of hCNT3. (PMID:17453413)
• 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)
• In NSCLC and normal tissues expression of hENT1 and hCNT1 ranged from completely negative to high. (PMID:18600541)
• We found a strong relationship between IHC staining of hCNT3 and clinical resistance to F-ara-A therapy in chronic lymphocytic leukemia. (PMID:18604194)
• Report expression and hepatobiliary transport characteristics of CNT1 in sandwich-cultured human hepatocytes. (PMID:18635603)
• In nonsmall cell lung cancer CNT1 565A showed a borderline significant positive influence on the early response for carriers of the variant allele which, however, did not translate to the survival of the patients (PMID:19107936)
• 5-azacytidine as a novel substrate for hCNT1 and provides direct evidence that hCNT1 is involved in the DNA-demethylating effects of this drug (PMID:19139132)
• The CNT1 promoter was characterized with respect to DNA response elements and their binding factors are reported. (PMID:19228884)
• Patients with low levels of hCNT1 achieved inferior clinical response. (PMID:19647871)
• variability in hCNT1 and hENT1 expression in tumour and normal human breast tissue with different expression patterns related to patient prognosis and clinical outcome. (PMID:20734919)
• Two pyrimidine nucleoside analogs were potent inhibitors of CNT1, with negligible transportability and little apparent cytotoxicity, suggesting that they may have utility as cytoprotective agents. (PMID:20854794)
• our findings identify hCNT1 as a potential candidate to render drug-resistant pancreatic cancer cells amenable to chemotherapy. (PMID:21343396)
• Site-directed mutagenesis analysis reveals that only one sodium binding site is affected by a mutation; lack of serine546 residue is responsible for apparent loss of CNT1 function. (PMID:21998139)
• MUC4 and hCNT1 as potential targets to ameliorate the response of pancreatic tumors to gemcitabine treatment. (PMID:22580602)
• CNT1-mediated gemcitabine uptake shows a higher correlation with the CNT1 expression level than does ENT1-mediated uptake with ENT1 expression. (PMID:22644860)
• Human CNT1 fits the profile of a transceptor in a substrate translocation-independent manner and is likely to be relevant to tumor biology. (PMID:23722537)
• hCNT1 is a putative determinant for nucleoside analog chemoresistance in ovarian cancer. (PMID:25600708)
• ErbB2 modulates gemcitabine and irinotecan/SN-38 chemoresistance of human pancreatic cancer cells via hCNT1 transporter and multidrug-resistance associated protein MRP-2. (PMID:25890497)
• Brazilian Amerindian ancestry compared to Asian, European, and African Genomes.SNPs within or proximal to CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch. SNPs in ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) in the Asian comparison. (PMID:28100790)
• 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)
• Expression of the nucleoside transporters hENT1 (SLC29) and hCNT1 (SLC28) in pediatric acute myeloid leukemia. (PMID:32312148)
• Characterization of deoxyribonucleoside transport mediated by concentrative nucleoside transporters. (PMID:33910126)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc28a1	ENSDARG00000060879
mus_musculus	Slc28a1	ENSMUSG00000025726
rattus_norvegicus	Slc28a1	ENSRNOG00000018940
drosophila_melanogaster	CNT2	FBGN0025709
drosophila_melanogaster	CNT1	FBGN0033371
caenorhabditis_elegans		WBGENE00017867
caenorhabditis_elegans		WBGENE00017868

Paralogs (2): SLC28A2 (ENSG00000137860), SLC28A3 (ENSG00000197506)

Protein

Protein identifiers

Sodium/nucleoside cotransporter 1 — O00337 (reviewed: O00337)

Alternative names: Concentrative nucleoside transporter 1, Na(+)/nucleoside cotransporter 1, Sodium-coupled nucleoside transporter 1, Solute carrier family 28 member 1

All UniProt accessions (2): O00337, B7Z3L6

UniProt curated annotations — full annotation on UniProt →

Function. Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient. Also transports adenosine, an atypical substrate transported with high apparent affinity, but low maximum velocity. Therefore, exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit). Involved in renal nucleoside (re)absorption.

Subcellular location. Cell membrane. Apical cell membrane.

Tissue specificity. Expressed in kidney.

Post-translational modifications. N-glycosylated. N-glycosylation is required for localization to the plasma membrane and the transporter activity.

Disease relevance. Uridine-cytidineuria (URCTU) [MIM:618477] An autosomal recessive inborn error of metabolism characterized by increased urinary uridine and cytidine excretion. It is a likely benign metabolic trait without clinical manifestations. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Due to its high apparent affinity but slow transport, adenosine could act as a negative regulator of pyrimidine transport under some conditions.

Polymorphism. All three alleles (A, B and C) have similar nucleoside transport activity.

Miscellaneous. Can also transport the antiviral pyrimidine nucleoside analogs 3’-azido-3’-deoxythymidine (AZT) and 2’,3’-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of pyrimidine nucleoside analogs used to treat acquired immunodeficiency syndrome (AIDS).

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00337-1	1	yes
O00337-2	2

RefSeq proteins (6): NP_001274690, NP_001274691, NP_001308650, NP_001308651, NP_004204, NP_964014 (=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)
• thymidine(out) + Na(+)(out) = thymidine(in) + Na(+)(in) (RHEA:69891)
• cytidine(out) + Na(+)(out) = cytidine(in) + Na(+)(in) (RHEA:69895)
• adenosine(out) + Na(+)(out) = adenosine(in) + Na(+)(in) (RHEA:69927)

UniProt features (47 total): topological domain 14, transmembrane region 13, sequence variant 10, mutagenesis site 5, glycosylation site 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00337-F1	81.94	0.49

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 (2): 605, 643

Mutagenesis-validated functional residues (5):

Position	Phenotype
318	changed pyrimidine- and adenosine-specific:sodium symporter activity. decreased specificity for pyrimidine nucleosides e
319	changed pyrimidine- and adenosine-specific:sodium symporter activity. loss of specificity for pyrimidine nucleosides; wh
352	changed pyrimidine- and adenosine-specific:sodium symporter activity. loss of specificity for pyrimidine nucleosides; wh
546	no effect on localization to the apical plasma membrane. loss of pyrimidine- and adenosine-specific:sodium symporter act
546	loss of pyrimidine- and adenosine-specific:sodium symporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 97 (showing top): MODULE_120, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORT, GOBP_NUCLEOSIDE_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_CARBOHYDRATE_DERIVATIVE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, MODULE_112, GOBP_AZOLE_TRANSMEMBRANE_TRANSPORT, SHEN_SMARCA2_TARGETS_DN, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOCC_CLUSTER_OF_ACTIN_BASED_CELL_PROJECTIONS

GO Biological Process (8): pyrimidine nucleobase transport (GO:0015855), cytidine transport (GO:0015861), uridine transmembrane transport (GO:0015862), azole transmembrane transport (GO:0045117), pyrimidine-containing compound transmembrane transport (GO:0072531), nucleoside import across plasma membrane (GO:0180015), nucleoside transmembrane transport (GO:1901642), purine nucleobase transmembrane transport (GO:1904823)

GO Molecular Function (8): purine nucleobase transmembrane transporter activity (GO:0005345), nucleoside:sodium symporter activity (GO:0005415), cytidine transmembrane transporter activity (GO:0015212), 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), symporter activity (GO:0015293)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), nuclear speck (GO:0016607), brush border membrane (GO:0031526), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
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
nucleoside transmembrane transport	3
transmembrane transport	3
pyrimidine nucleoside transport	2
nitrogen compound transport	2
pyrimidine nucleoside transmembrane transporter activity	2
cellular anatomical structure	2
nucleobase transport	1
pyrimidine-containing compound transmembrane transport	1
import across plasma membrane	1
nucleoside transport	1
purine nucleobase transport	1
purine-containing compound transmembrane transport	1
nucleobase transmembrane transporter activity	1
purine nucleobase transmembrane transport	1
nucleoside transmembrane transporter activity	1
solute:sodium symporter activity	1
cytidine transport	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
transmembrane transporter activity	1
azole transmembrane transport	1
nucleobase-containing compound transmembrane transporter activity	1
carbohydrate derivative transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
cytoplasm	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
nuclear ribonucleoprotein granule	1
brush border	1
apical plasma membrane	1
cell projection membrane	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC28A1	SLC29A1	Q99808	894
SLC28A1	SLC29A2	Q14542	893
SLC28A1	SLC22A1	O15245	860
SLC28A1	SLC29A3	Q9BZD2	747
SLC28A1	SLC29A4	Q7RTT9	701
SLC28A1	DCK	P27707	668
SLC28A1	CDA	P32320	637
SLC28A1	DCTD	P32321	540
SLC28A1	SLC22A4	Q9H015	539
SLC28A1	SLC22A7	Q9Y694	539
SLC28A1	ABCC5	O15440	528
SLC28A1	TYMS	P04818	522
SLC28A1	RAB10	P61026	507
SLC28A1	RRM1	P23921	483
SLC28A1	SLC22A5	O76082	479

IntAct

3 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350
SLC28A1	POLR3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): SLC28A1 (Positive Genetic), ALDH3A2 (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5L (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5J (Affinity Capture-MS), ATRN (Affinity Capture-MS), C17orf80 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CHAF1B (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS), HADHA (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0A0G2KQY6, A0A6I8PMZ8, A0JPN2, A4IGY6, A5D7L5, B2RXE2, E9PU17, E9PX95, E9PXX9, G3X943, O00337, O43868, O88627, O94402, P02730, P04919, P0DX17, P23562, P55205, P97441, Q08E40, Q0DWA9, Q0VCH8, Q14940, Q15043, Q4VAE3, Q504Y0, Q5FVQ0, Q5FWH7, Q5RAB7, Q5Z413, Q62674, Q62773, Q6L8F3, Q6PI78, Q6TL19, Q75N73, Q78IQ7, Q8HYW2

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	9
Benign	22

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
687710	GRCh37/hg19 15q25.2-25.3(chr15:84884801-85724984)x1	Pathogenic

SpliceAI

3649 predictions. Top by Δscore:

Variant	Effect	Δscore
15:84884750:GG:G	donor_gain	1.0000
15:84884751:GG:G	donor_gain	1.0000
15:84904095:AGG:A	acceptor_gain	1.0000
15:84904096:GGG:G	acceptor_gain	1.0000
15:84904234:GCGCA:G	donor_gain	1.0000
15:84904236:GCA:G	donor_gain	1.0000
15:84904239:G:GG	donor_gain	1.0000
15:84908714:TCAG:T	acceptor_loss	1.0000
15:84908716:A:C	acceptor_loss	1.0000
15:84908717:G:A	acceptor_loss	1.0000
15:84908778:G:GT	donor_gain	1.0000
15:84908791:TTCAG:T	donor_loss	1.0000
15:84908792:TCAGG:T	donor_loss	1.0000
15:84908793:CAGGT:C	donor_loss	1.0000
15:84908794:AGGTC:A	donor_loss	1.0000
15:84908795:GG:G	donor_loss	1.0000
15:84908797:T:G	donor_loss	1.0000
15:84908859:G:GT	donor_gain	1.0000
15:84908859:G:T	donor_gain	1.0000
15:84918603:AGG:A	donor_loss	1.0000
15:84918604:GGTAA:G	donor_loss	1.0000
15:84918605:GTA:G	donor_loss	1.0000
15:84918606:T:A	donor_loss	1.0000
15:84920984:TCTAG:T	acceptor_loss	1.0000
15:84920986:TAG:T	acceptor_loss	1.0000
15:84920987:A:AG	acceptor_gain	1.0000
15:84920987:A:G	acceptor_loss	1.0000
15:84920988:G:GA	acceptor_gain	1.0000
15:84920988:G:T	acceptor_loss	1.0000
15:84920988:GATT:G	acceptor_gain	1.0000

AlphaMissense

4223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:84943484:T:C	F541L	0.995
15:84943486:T:A	F541L	0.995
15:84943486:T:G	F541L	0.995
15:84921064:A:C	S318R	0.992
15:84921066:C:A	S318R	0.992
15:84921066:C:G	S318R	0.992
15:84924081:A:C	S352R	0.990
15:84924083:C:A	S352R	0.990
15:84924083:C:G	S352R	0.990
15:84943496:A:C	S545R	0.990
15:84943498:C:A	S545R	0.990
15:84943498:C:G	S545R	0.990
15:84943492:T:A	N543K	0.989
15:84943492:T:G	N543K	0.989
15:84933185:C:A	A375D	0.987
15:84935448:T:C	L504P	0.986
15:84943506:G:A	G548E	0.985
15:84921040:A:C	S310R	0.983
15:84921042:T:A	S310R	0.983
15:84921042:T:G	S310R	0.983
15:84905563:G:A	G210R	0.982
15:84905563:G:C	G210R	0.982
15:84943482:G:A	G540E	0.981
15:84918548:A:C	S274R	0.980
15:84918550:C:A	S274R	0.980
15:84918550:C:G	S274R	0.980
15:84924067:C:A	A347D	0.980
15:84935436:C:A	A500D	0.980
15:84935425:C:A	N496K	0.979
15:84935425:C:G	N496K	0.979

dbSNP variants (sampled 300 via entrez): RS1000021107 (15:84887274 A>G), RS1000067574 (15:84908308 C>G), RS1000068968 (15:84900417 AAAAAAAAG>A), RS1000149011 (15:84927425 G>A), RS1000204146 (15:84927567 T>G), RS1000228073 (15:84886756 C>A,T), RS1000236629 (15:84931109 T>C), RS1000259106 (15:84886456 T>G), RS1000261525 (15:84902294 A>C,G), RS1000332397 (15:84974138 C>T), RS1000369999 (15:84927173 C>T), RS1000417424 (15:84925058 G>A), RS1000427900 (15:84965523 T>C), RS1000448413 (15:84972328 T>G), RS1000473960 (15:84890044 A>G)

Disease associations

OMIM: gene MIM:606207 | disease phenotypes: MIM:618477

GenCC curated gene-disease

Mondo (1): uridine-cytidineuria (MONDO:0032773)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0032573	Elevated urinary cytidine
HP:0032574	Elevated urinary uridine level

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001280_12	Alzheimer’s disease (age of onset)	9.000000e-06
GCST001280_6	Alzheimer’s disease (age of onset)	9.000000e-06
GCST002830_30	Urate levels in lean individuals	8.000000e-06
GCST004521_253	Autism spectrum disorder or schizophrenia	6.000000e-11
GCST004635_29	Testicular germ cell tumor	5.000000e-08
GCST005979_3	Systolic blood pressure	3.000000e-08
GCST006979_938	Heel bone mineral density	2.000000e-09
GCST007703_47	Systolic blood pressure	1.000000e-07
GCST007706_119	Mean arterial pressure	3.000000e-07
GCST008103_25	Bipolar disorder	3.000000e-08
GCST012020_196	Serum metabolite levels	4.000000e-15
GCST012020_197	Serum metabolite levels	8.000000e-11
GCST012020_198	Serum metabolite levels	1.000000e-17
GCST012020_199	Serum metabolite levels	3.000000e-12
GCST012021_71	Serum metabolite levels	4.000000e-15
GCST012021_72	Serum metabolite levels	8.000000e-11
GCST012021_73	Serum metabolite levels	1.000000e-17
GCST012021_74	Serum metabolite levels	3.000000e-12
GCST012226_539	Waist circumference adjusted for body mass index	1.000000e-13
GCST012226_540	Waist circumference adjusted for body mass index	2.000000e-12
GCST012226_541	Waist circumference adjusted for body mass index	1.000000e-08
GCST012228_501	Waist-hip index	2.000000e-09
GCST012228_502	Waist-hip index	4.000000e-08
GCST012230_144	Waist-to-hip ratio adjusted for BMI	6.000000e-09
GCST012231_133	A body shape index	1.000000e-10
GCST012231_134	A body shape index	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004531	urate measurement
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0006340	mean arterial pressure
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5551 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 325,400 (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
CHEMBL392149	TECADENOSON	2	382

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12148896	Toxicity	3	gemcitabine	Neutropenia;Pancreatic Neoplasms
rs2242046	Toxicity	3	gemcitabine	Non-Small Cell Lung Carcinoma
rs2290271	Toxicity	4	anthracyclines and related substances
rs2305364	Toxicity	4	anthracyclines and related substances	Neoplasms
rs3825876	Toxicity	3	gemcitabine	Neutropenia;Pancreatic Neoplasms

PharmGKB variants

11 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2242046	SLC28A1	3	1.75	1	gemcitabine
rs2242047	SLC28A1		0.00	0
rs2242048	SLC28A1		0.00	0
rs2290271	SLC28A1	4	-1.50	1	anthracyclines and related substances
rs2290272	SLC28A1		0.00	0
rs2305364	SLC28A1	4	-1.50	1	anthracyclines and related substances
rs8187758	SLC28A1		0.00	0
rs11853372	SLC28A1		0.00	0
rs17215836	SLC28A1		0.00	0
rs3825876	SLC28A1	3	2.75	1	gemcitabine
rs12148896	SLC28A1	3	2.75	1	gemcitabine

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC28 family

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.43	IC50	370	nM	CHEMBL5084426
5.75	Ki	1800	nM	ADENOSINE
5.28	Ki	5200	nM	URIDINE
5.26	IC50	5500	nM	ADENOSINE
5.24	IC50	5800	nM	URIDINE

PubChem BioAssay actives

4 with measured affinity, of 13 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
Adenosine	1222907: Binding affinity to recombinant human CNT1 expressed in Saccharomyces cerevisiae assessed as inhibition of [3H]-uridine transport after 15 mins by scintillation counting analysis	ki	1.8000	uM
Uridine	1222907: Binding affinity to recombinant human CNT1 expressed in Saccharomyces cerevisiae assessed as inhibition of [3H]-uridine transport after 15 mins by scintillation counting analysis	ki	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, increases methylation, affects expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cytidine	increases uptake, increases transport, decreases reaction	2
Sodium	affects reaction, increases uptake	2
Uridine	decreases reaction, increases uptake, increases transport, affects reaction	2
bisphenol A	affects cotreatment, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
clothianidin	increases expression	1
Rosiglitazone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Gemcitabine	decreases reaction, increases transport	1
Adenosine	decreases reaction, increases uptake, affects transport	1
Atrazine	increases expression	1
Azacitidine	increases response to substance, increases uptake, decreases expression, affects reaction	1
Cytarabine	decreases reaction, increases transport	1
Deoxycytidine	increases transport	1
Formaldehyde	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Thymidine	decreases reaction, increases uptake	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1

ChEMBL screening assays

7 unique, capped per target: 5 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3528992	ADMET	Binding affinity to recombinant human CNT1 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
CHEMBL5233329	Binding	Inhibition of human CNT1	Expanding the repertoire of methanocarba nucleosides from purinergic signaling to diverse targets. — RSC Med Chem

Clinical trials (associated diseases)

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