SLC2A2

Summary

SLC2A2 (solute carrier family 2 member 2, HGNC:11006) is a protein-coding gene on chromosome 3q26.2, encoding Solute carrier family 2, facilitated glucose transporter member 2 (P11168). Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose.

This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 6514 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycogen storage disease due to GLUT2 deficiency (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 385 total — 38 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11006
Approved symbol	SLC2A2
Name	solute carrier family 2 member 2
Location	3q26.2
Locus type	gene with protein product
Status	Approved
Aliases	GLUT-2
Ensembl gene	ENSG00000163581
Ensembl biotype	protein_coding
OMIM	138160
Entrez	6514

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000314251, ENST00000461867, ENST00000469787, ENST00000471379, ENST00000497642, ENST00000878396, ENST00000878397, ENST00000878398, ENST00000878399, ENST00000878400, ENST00000878401, ENST00000878402

RefSeq mRNA: 3 — MANE Select: NM_000340 NM_000340, NM_001278658, NM_001278659

CCDS: CCDS3215

Canonical transcript exons

ENST00000314251 — 11 exons

Exon	Start	End
ENSE00001204130	170996347	170998103
ENSE00001213480	171014469	171014731
ENSE00001839148	171026656	171026720
ENSE00003507103	170999065	170999166
ENSE00003511861	171005943	171006105
ENSE00003526942	170998193	170998396
ENSE00003549768	171002576	171002680
ENSE00003590791	171005285	171005472
ENSE00003593217	171009958	171010082
ENSE00003600739	171007148	171007263
ENSE00003689114	171018531	171018623

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 98.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.5072 / max 1056.8565, expressed in 44 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45573	3.5072	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.05	gold quality
liver	UBERON:0002107	97.71	gold quality
jejunal mucosa	UBERON:0000399	95.90	gold quality
duodenum	UBERON:0002114	91.73	gold quality
ileal mucosa	UBERON:0000331	88.64	gold quality
nephron tubule	UBERON:0001231	86.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.82	gold quality
islet of Langerhans	UBERON:0000006	80.87	gold quality
kidney epithelium	UBERON:0004819	80.50	gold quality
adult mammalian kidney	UBERON:0000082	79.55	gold quality
renal glomerulus	UBERON:0000074	77.77	gold quality
metanephric glomerulus	UBERON:0004736	77.63	gold quality
gall bladder	UBERON:0002110	76.86	gold quality
small intestine	UBERON:0002108	76.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.32	gold quality
kidney	UBERON:0002113	75.00	gold quality
jejunum	UBERON:0002115	71.12	gold quality
cortex of kidney	UBERON:0001225	68.89	gold quality
pancreas	UBERON:0001264	68.56	gold quality
epithelial cell of pancreas	CL:0000083	67.19	gold quality
metanephros	UBERON:0000081	65.57	gold quality
corpus callosum	UBERON:0002336	64.05	gold quality
body of pancreas	UBERON:0001150	63.55	gold quality
cerebellar vermis	UBERON:0004720	55.91	gold quality
metanephros cortex	UBERON:0010533	53.78	gold quality
renal medulla	UBERON:0000362	52.80	silver quality
adrenal tissue	UBERON:0018303	52.13	gold quality
adult organism	UBERON:0007023	50.73	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, CEBPG, EP300, ESR1, FOXA2, FOXA3, FOXM1, HNF1A, HNF1B, HNF4A, JUN, MAFA, MITF, NKX6-1, NR1H2, ONECUT1, PAX6, PDX1, PPARA, PPARG, SP1, SREBF1, STAT1, STAT3, ZNF236

miRNA regulators (miRDB)

95 targeting SLC2A2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• mutated in patients with fanconi-Bickel syndrome (PMID:11810292)
• Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. (PMID:11978637)
• polymorphisms at positions -269, -44, or + 103 may affect GLUT2 gene transcription, possibly associated with reduced expression of the GLUT2 gene in NIDDM patients. (PMID:12017192)
• Expression is responsible for resistance to alloxan and streptozotocin toxicity. (PMID:14614558)
• We have found GLUT-2 and glucokinase mRNAs in several brain regions, including the ventromedial and arcuate nuclei of the hypothalamus (PMID:15009676)
• SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with impaired glucose tolerance. (PMID:15983230)
• identify Glut2 as a GroPIns transporter in mammals, and define a physiologically relevant cell-permeation mechanism (PMID:17141226)
• kidney of diabetic rats, an initial and transient upregulation of GLUT2 was induced specifically by insulin only. (PMID:17204838)
• recent progress in elucidating the transcriptional regulation of GLUT2 in the liver and pancreatic beta-cells and the relevance to type 2 diabetes.[RREVIEW] (PMID:18220613)
• Data show that glucose transport in human airway epithelial cells in vitro and in vivo utilises GLUT2 transporters, and suggest that these transporters could contribute to glucose uptake/homeostasis in the human airway. (PMID:18239936)
• Our findings show that a genetic variation in GLUT2 is associated with habitual consumption of sugars, suggesting an underlying glucose-sensing mechanism that regulates food intake. (PMID:18349384)
• The contribution of GLUT2 to human metabolic diseases (Review) (PMID:19223655)
• combined presence of rs5393 & rs5394 polymorphisms of GLUT2 was more frequent in type 2 diabetics than non-diabeteics; rs5394 appeared to be associated with decreased glucose stimulated insulin release & a tendency to a reduced GLUT2 gene expression (PMID:19269875)
• HCV replication down-regulates cell surface expression of GLUT2 partly at the transcriptional level, and possibly at the intracellular trafficking level as suggested for GLUT1, thereby lowering glucose uptake by hepatocytes. (PMID:19303158)
• The expression pattern of GLUT2 is reported in newly diagnosed esophageal adenocarcinoma by means of immunohistochemistry. (PMID:19554504)
• Genetic polymorphisms of SLC2A2 and HP is associated with serum cholesterol levels. (PMID:20066028)
• prostate cancer was inversely associated with the SLC2A2 rs5400 Thr110 allele (PMID:20142250)
• Intestinal glucose absorption by the apical GLUT2 pathway can be 3 to 5-times greater then by SGLT1 et the high concentration of sugar. (PMID:20201351)
• Polyphenols, phenolic acids and tannins from strawberry and apple are potent inhibitors of GLUT2 and SGLT1 at concentrations predicted after dietary ingestion. (PMID:20564476)
• In human enterocytes, GLUT2 was consistently located in basolateral membranes; mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. (PMID:21852673)
• SLC2A1 and SLC2A3 predominate in both human islets and beta-cells their expression level was 2.8 and 2.7 fold higher than SLC2A2 respectively and GLUT2 is therefore unlikely to be the principal glucose transporter in human beta-cells (PMID:21920790)
• Constitutive expression of GLUT2 in the apical membrane along with additional translocation of cytoplasmic GLUT2 to the apical membrane via an intact cytoskeleton and activated PKC appears responsible for enhanced carrier-mediated glucose uptake. (PMID:21943636)
• We report the first Chinese cases of Fanconi-Bickel syndrome (FBS),a rare inherited disease caused by mutations in the glucose transporter 2 gene, SLC2A2. (PMID:22145468)
• report on two siblings with Fanconi-Bickel syndrome (FBS) and an unusually mild clinical course; both patients were found to be compound heterozygous for the novel GLUT2 (SLC2A2) mutations c.457_462delCTTATA (p.153_4delLI) and c.1250C>G (p.P417R) (PMID:22214819)
• enhanced expression of GLUT1 and GLUT2 during differentiation of human embryonic stem cells (PMID:22221271)
• Mutation analysis of the GLUT2 gene in three unrelated Egyptian families with Fanconi-Bickel syndrome detected three different mutations. (PMID:22350464)
• The finding that patients with homozygous SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the human beta cell. (PMID:22660720)
• Homozygous mutations in GLUT2, which cause Fanconi-Bickel syndrome, can lead to very different clinical and biochemical findings that are not limited to mild proximal renal tubulopathy but can include significant hypercalciuria. (PMID:22865906)
• GLUT2 gene expression is suppressed in Hepatitis C virus infection via downregulation of HNF-1alpha expression at transcriptional and posttranslational levels. (PMID:22993150)
• Case-control analyses revealed a unique association between the G allele of rs9875793 and bipolar disorder patients with ’negative mood delusions’ compared with controls. (PMID:23010768)
• Genetic variant SLC2A2 is marginally associated with risk of cardiovascular disease in type 2 diabetes mellitus patients. (PMID:23185617)
• associated with caries risk (PMID:23257979)
• This study determined if single nucleotide polymorphisms in genes involved in fructose transport,SLC2A2 and SLC2A5 and metabolism, etohexokinase affect inter-individual variability in metabolic phenotypes. (PMID:23341889)
• Intestinal dehydroascorbic acid (DHA) transport is mediated by the facilitative sugar transporters, GLUT2 and GLUT8 (PMID:23396969)
• the first gain of function mutations for hGLUT2, revealing the importance of its receptor versus transporter function in pancreatic beta cell development and insulin secretion. (PMID:23986439)
• SGLT1 mRNA and GLUT2 mRNA expression are reduced significantly in CACo-2 cells exposed to berry extracts. (PMID:24236070)
• GLUT-2 expression may be associated with cholangiocarcinogenesis of large bile duct and is a helpful marker for detecting high-grade biliary intraepithelial neoplasia lesions in atypical bile ducts. (PMID:24824030)
• Mutations in the GLUT2 gene is associated with ccute metabolic acidosis in Fanconi-Bickel syndrome. (PMID:25165176)
• A novel 6 nucleotide deletion in GLUT2 gene, a member of the facilitative glucose transporter family, is shown to be segregated with Fanconi-Bickel syndrome in an Iranian family. (PMID:25523092)
• Data identified the last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)and the putative tyrosine phosphatase PTPLAD1 as new regulators of Glut2(SLC2A2)translocation in HEK293 cells. SiRNA-mediated knockdown of ATIC delayed insulin response of Glut2 translocation while depletion of PTPLAD1(HACD3} strongly enhanced it in HEK293 cells. (PMID:25687571)

Cross-species orthologs

45 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc2a2	ENSDARG00000056196
mus_musculus	Slc2a2	ENSMUSG00000027690
rattus_norvegicus	Slc2a2	ENSRNOG00000011875
drosophila_melanogaster	Glut3	FBGN0015230
drosophila_melanogaster	sut4	FBGN0028560
drosophila_melanogaster	sut3	FBGN0028561
drosophila_melanogaster	sut2	FBGN0028562
drosophila_melanogaster	sut1	FBGN0028563
drosophila_melanogaster	CG4607	FBGN0029932
drosophila_melanogaster	CG15406	FBGN0031517
drosophila_melanogaster	CG8837	FBGN0031520
drosophila_melanogaster	CG3285	FBGN0031522
drosophila_melanogaster	CG15408	FBGN0031523
drosophila_melanogaster	CG7882	FBGN0033047
drosophila_melanogaster	Tret1-2	FBGN0033644
drosophila_melanogaster	CG8249	FBGN0034045
drosophila_melanogaster	CG6484	FBGN0034247
drosophila_melanogaster	CG14160	FBGN0036066
drosophila_melanogaster	nebu	FBGN0036316
drosophila_melanogaster	CG1208	FBGN0037386
drosophila_melanogaster	CG14606	FBGN0037485
drosophila_melanogaster	CG14605	FBGN0037486
drosophila_melanogaster	CG6901	FBGN0038414
drosophila_melanogaster	CG17929	FBGN0038415
drosophila_melanogaster	CG17930	FBGN0038416
drosophila_melanogaster	Tret1-1	FBGN0050035
drosophila_melanogaster	CG32053	FBGN0052053
drosophila_melanogaster	CG32054	FBGN0052054
drosophila_melanogaster	CG33281	FBGN0053281
drosophila_melanogaster	CG33282	FBGN0053282
drosophila_melanogaster	Srg2	FBGN0262007
drosophila_melanogaster	CG42826	FBGN0262008
caenorhabditis_elegans		WBGENE00008730
caenorhabditis_elegans		WBGENE00010684
caenorhabditis_elegans		WBGENE00010811
caenorhabditis_elegans		WBGENE00012536
caenorhabditis_elegans		WBGENE00013074
caenorhabditis_elegans		WBGENE00016431
caenorhabditis_elegans		WBGENE00017382
caenorhabditis_elegans		WBGENE00019207
caenorhabditis_elegans		WBGENE00019547
caenorhabditis_elegans		WBGENE00019548
caenorhabditis_elegans		WBGENE00019549
caenorhabditis_elegans		WBGENE00019550
caenorhabditis_elegans		WBGENE00043980

Paralogs (13): SLC2A3 (ENSG00000059804), SLC2A9 (ENSG00000109667), SLC2A1 (ENSG00000117394), SLC2A11 (ENSG00000133460), SLC2A8 (ENSG00000136856), SLC2A5 (ENSG00000142583), SLC2A12 (ENSG00000146411), SLC2A13 (ENSG00000151229), SLC2A6 (ENSG00000160326), SLC2A14 (ENSG00000173262), SLC2A4 (ENSG00000181856), SLC2A7 (ENSG00000197241), SLC2A10 (ENSG00000197496)

Protein

Protein identifiers

Solute carrier family 2, facilitated glucose transporter member 2 — P11168 (reviewed: P11168)

Alternative names: Glucose transporter type 2, liver

All UniProt accessions (4): A0A0C4DH64, C9J0E8, P11168, F8WBJ2

UniProt curated annotations — full annotation on UniProt →

Function. Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose. Likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of beta cells. May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney. Also able to mediate the transport of dehydroascorbate and urate.

Subcellular location. Cell membrane.

Tissue specificity. Liver, insulin-producing beta cell, small intestine and kidney.

Post-translational modifications. N-glycosylated; required for stability and retention at the cell surface of pancreatic beta cells.

Disease relevance. Fanconi-Bickel syndrome (FBS) [MIM:227810] Rare, well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. D-glucose and maltose competitively inhibit fructose transport. D-glucose, D-fructose and maltose inhibit deoxyglucose transport. Glucose and fructose transport are inhibited by flavonoids such as epigallocatechin gallate, apigenin and quercetin.

Similarity. Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P11168-1	1	yes
P11168-2	2

RefSeq proteins (3): NP_000331, NP_001265587, NP_001265588 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002440	Glc_transpt_2	Family
IPR003663	Sugar/inositol_transpt	Family
IPR005828	MFS_sugar_transport-like	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR045263	GLUT	Family

Pfam: PF00083

Catalyzed reactions (Rhea), 5 shown:

• D-galactose(in) = D-galactose(out) (RHEA:34915)
• urate(out) = urate(in) (RHEA:60368)
• D-fructose(out) = D-fructose(in) (RHEA:60372)
• D-glucose(out) = D-glucose(in) (RHEA:60376)
• L-dehydroascorbate(out) = L-dehydroascorbate(in) (RHEA:60380)

UniProt features (48 total): topological domain 13, transmembrane region 12, sequence variant 9, binding site 6, sequence conflict 3, chain 1, modified residue 1, glycosylation site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11168-F1	86.56	0.65

Functional residue map

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

Ligand- & substrate-binding residues (6): 193; 314–315; 320; 349; 412; 420

Post-translational modifications (1): 523

Glycosylation sites (1): 62

Mutagenesis-validated functional residues (1):

Position	Phenotype
322	reduced fructose transport.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-210745	Regulation of gene expression in beta cells
R-HSA-422356	Regulation of insulin secretion
R-HSA-5619098	Defective SLC2A2 causes Fanconi-Bickel syndrome (FBS)
R-HSA-8981373	Intestinal hexose absorption

MSigDB gene sets: 297 (showing top): GOBP_CARBOHYDRATE_TRANSPORT, PID_HNF3B_PATHWAY, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, LEE_LIVER_CANCER_CIPROFIBRATE_DN, chr3q26, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, UEDA_PERIFERAL_CLOCK, HOSHIDA_LIVER_CANCER_SUBCLASS_S3

GO Biological Process (8): carbohydrate metabolic process (GO:0005975), fructose transmembrane transport (GO:0015755), galactose transmembrane transport (GO:0015757), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), obsolete D-glucose import (GO:0046323), dehydroascorbic acid transport (GO:0070837), D-glucose transmembrane transport (GO:1904659), transmembrane transport (GO:0055085)

GO Molecular Function (6): fructose transmembrane transporter activity (GO:0005353), galactose transmembrane transporter activity (GO:0005354), hexose transmembrane transporter activity (GO:0015149), dehydroascorbic acid transmembrane transporter activity (GO:0033300), D-glucose transmembrane transporter activity (GO:0055056), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): cytoplasm (GO:0005737), plasma membrane (GO:0005886), brush border (GO:0005903), cell-cell junction (GO:0005911), membrane (GO:0016020), apical plasma membrane (GO:0016324), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Regulation of beta-cell development	1
Integration of energy metabolism	1
SLC transporter disorders	1
Intestinal absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hexose transmembrane transport	4
cellular anatomical structure	4
hexose transmembrane transporter activity	3
apical part of cell	2
sperm flagellum	2
primary metabolic process	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
vitamin transport	1
transport	1
cellular process	1
fructose transmembrane transport	1
galactose transmembrane transport	1
monosaccharide transmembrane transporter activity	1
dehydroascorbic acid transport	1
vitamin transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
microvillus	1
cluster of actin-based cell projections	1
anchoring junction	1
plasma membrane region	1

Protein interactions and networks

STRING

2716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC2A2	GCK	P35557	960
SLC2A2	INS	P01308	941
SLC2A2	SLC5A1	P13866	889
SLC2A2	GCG	P01275	871
SLC2A2	NEUROD1	Q13562	863
SLC2A2	NKX6-1	P78426	861
SLC2A2	NEUROG3	Q9Y4Z2	852
SLC2A2	NKX6-2	Q9C056	833
SLC2A2	G6PC2	Q9NQR9	818
SLC2A2	KCNJ11	Q14654	814
SLC2A2	SLC5A2	P31639	812
SLC2A2	PAX4	O43316	803
SLC2A2	ABCC8	Q09428	801
SLC2A2	G6PC3	Q9BUM1	794
SLC2A2	MAFA	Q8NHW3	779

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FAM20C	SLC2A2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SLC2A2	ST3GAL2	psi-mi:“MI:0915”(physical association)	0.400
SLC2A2	APOB	psi-mi:“MI:0914”(association)	0.350
SLC2A2	CAPG	psi-mi:“MI:0914”(association)	0.350
SLC2A2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (117): TRUB1 (Affinity Capture-MS), APOB (Affinity Capture-MS), SLC2A2 (Synthetic Lethality), SLC2A2 (Reconstituted Complex), SLC2A2 (Affinity Capture-Western), UFD1L (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), NUDT9 (Affinity Capture-MS), TRUB1 (Affinity Capture-MS), CAPG (Affinity Capture-MS), ST3GAL2 (Affinity Capture-MS), SLC2A2 (Affinity Capture-MS), SLC2A2 (Cross-Linking-MS (XL-MS)), ABCB6 (Affinity Capture-MS), ABCC1 (Affinity Capture-MS)

ESM2 similar proteins: A4ZYQ5, O35956, O57379, O62786, O62787, P0C6A1, P11166, P11167, P11168, P11169, P12336, P13355, P14142, P14246, P14672, P17809, P19357, P20303, P22732, P27674, P28568, P32037, P43427, P46896, P47842, P47843, P58351, P58352, P58353, P79365, Q07647, Q27994, Q28ES4, Q5R608, Q5RET7, Q66J52, Q6A4L0, Q6DFR1, Q6NUB3, Q6NYN7

Diamond homologs: A1Z8N1, A4ZYQ5, A5LGM7, A9ZSY3, B3MG58, B3NSE1, B4HNS0, B4HNS1, B4J913, B4KR05, B4LPX5, B4P624, B4QBN2, B4QBN3, C0SPB2, O44616, O44827, O62786, O62787, P0C6A1, P11166, P11167, P11168, P11169, P12336, P13355, P14142, P14246, P14672, P17809, P19357, P20303, P22732, P27674, P28568, P32037, P32466, P43427, P46333, P46408

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MAFA	“up-regulates quantity by expression”	SLC2A2	“transcriptional regulation”
SLC2A2	“up-regulates quantity”	α-D-glucose	relocalization
SLC2A2	“up-regulates quantity”	glucose	relocalization
PDX1	“up-regulates quantity by expression”	SLC2A2	“transcriptional regulation”
streptozocin	“down-regulates quantity”	SLC2A2	“chemical inhibition”
PKA	“down-regulates activity”	SLC2A2	phosphorylation
PRKACA	“down-regulates activity”	SLC2A2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	16
Uncertain significance	164
Likely benign	97
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1045992	NM_000340.2(SLC2A2):c.1359T>A (p.Cys453Ter)	Pathogenic
1339447	NM_000340.2(SLC2A2):c.2T>G (p.Met1Arg)	Pathogenic
1339448	NM_000340.2(SLC2A2):c.144del (p.Pro49fs)	Pathogenic
1355333	NM_000340.2(SLC2A2):c.1280del (p.Phe427fs)	Pathogenic
1434311	NC_000003.11:g.(?170727727)(170727891_?)del	Pathogenic
1451164	NM_000340.2(SLC2A2):c.1170+1G>T	Pathogenic
16091	NM_000340.2(SLC2A2):c.137del (p.Leu46fs)	Pathogenic
16092	NM_000340.2(SLC2A2):c.1093C>T (p.Arg365Ter)	Pathogenic
16093	NM_000340.2(SLC2A2):c.901C>T (p.Arg301Ter)	Pathogenic
16096	NM_000340.2(SLC2A2):c.1259G>A (p.Trp420Ter)	Pathogenic
16097	NM_000340.2(SLC2A2):c.1051del (p.Val351fs)	Pathogenic
16098	SLC2A2, 1-BP INS, 793C	Pathogenic
16099	NM_000340.2(SLC2A2):c.952G>A (p.Gly318Arg)	Pathogenic
16100	NM_000340.2(SLC2A2):c.157C>T (p.Arg53Ter)	Pathogenic
16101	NM_000340.2(SLC2A2):c.1268T>A (p.Val423Glu)	Pathogenic
16102	NM_000340.2(SLC2A2):c.109-2A>G	Pathogenic
16103	NM_000340.2(SLC2A2):c.859C>T (p.Gln287Ter)	Pathogenic
16104	NM_000340.2(SLC2A2):c.1166T>C (p.Leu389Pro)	Pathogenic
1686207	NM_000340.2(SLC2A2):c.682C>T (p.Arg228Ter)	Pathogenic
1687276	NM_000340.2(SLC2A2):c.351G>A (p.Trp117Ter)	Pathogenic
2422929	NC_000003.11:g.(?170732238)(170732540_?)del	Pathogenic
2572454	NM_000340.2(SLC2A2):c.482dup (p.Gly162fs)	Pathogenic
2815922	NM_000340.2(SLC2A2):c.1183del (p.Trp395fs)	Pathogenic
2832588	NM_000340.2(SLC2A2):c.1392T>A (p.Tyr464Ter)	Pathogenic
3367193	NM_000340.2(SLC2A2):c.1020T>G (p.Tyr340Ter)	Pathogenic
3588928	NM_000340.2(SLC2A2):c.775+1del	Pathogenic
3588943	NM_000340.2(SLC2A2):c.2T>C (p.Met1Thr)	Pathogenic
3647230	NM_000340.2(SLC2A2):c.666_667del (p.Gly223fs)	Pathogenic
427888	NM_000340.2(SLC2A2):c.625G>T (p.Glu209Ter)	Pathogenic
444008	NM_000340.2(SLC2A2):c.963+1G>A	Pathogenic

SpliceAI

1295 predictions. Top by Δscore:

Variant	Effect	Δscore
3:171002569:GACTT:G	donor_loss	1.0000
3:171002570:ACTTA:A	donor_loss	1.0000
3:171002571:CTT:C	donor_loss	1.0000
3:171002572:TTA:T	donor_loss	1.0000
3:171002573:T:TG	donor_loss	1.0000
3:171002574:A:AC	donor_gain	1.0000
3:171002575:C:A	donor_loss	1.0000
3:171002575:C:CT	donor_gain	1.0000
3:171002575:CA:C	donor_gain	1.0000
3:171002575:CAG:C	donor_gain	1.0000
3:171002575:CAGAG:C	donor_gain	1.0000
3:171002676:AAAAT:A	acceptor_gain	1.0000
3:171002677:AAAT:A	acceptor_gain	1.0000
3:171002678:AAT:A	acceptor_gain	1.0000
3:171002679:AT:A	acceptor_gain	1.0000
3:171002681:C:CA	acceptor_loss	1.0000
3:171002681:C:CC	acceptor_gain	1.0000
3:171005278:AACTT:A	donor_loss	1.0000
3:171005279:ACTT:A	donor_loss	1.0000
3:171005280:CTTAC:C	donor_loss	1.0000
3:171005281:TTACG:T	donor_loss	1.0000
3:171005282:TACG:T	donor_loss	1.0000
3:171005283:A:AC	donor_gain	1.0000
3:171005283:A:C	donor_loss	1.0000
3:171005283:ACG:A	donor_gain	1.0000
3:171005283:ACGC:A	donor_gain	1.0000
3:171005284:C:CA	donor_gain	1.0000
3:171005284:C:T	donor_loss	1.0000
3:171005284:CG:C	donor_gain	1.0000
3:171005284:CGC:C	donor_gain	1.0000

AlphaMissense

3417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:171005992:G:C	S242R	0.995
3:171005992:G:T	S242R	0.995
3:171005994:T:G	S242R	0.995
3:171005295:C:T	G318E	0.992
3:170998326:C:T	G414E	0.991
3:170999100:A:G	C379R	0.991
3:171007151:A:C	S203R	0.991
3:171007151:A:T	S203R	0.991
3:171007153:T:G	S203R	0.991
3:170998367:G:C	S400R	0.990
3:170998367:G:T	S400R	0.990
3:170998369:T:G	S400R	0.990
3:170998327:C:G	G414R	0.988
3:170998327:C:T	G414R	0.988
3:170998340:G:C	S409R	0.988
3:170998340:G:T	S409R	0.988
3:170998342:T:G	S409R	0.988
3:170998263:G:T	A435D	0.987
3:171002647:C:G	A333P	0.987
3:170998327:C:A	G414W	0.986
3:170999079:C:G	G386R	0.986
3:170999079:C:T	G386R	0.986
3:170999141:C:G	R365P	0.986
3:170999121:C:G	G372R	0.984
3:170999121:C:T	G372R	0.984
3:171006066:A:G	W218R	0.984
3:171006066:A:T	W218R	0.984
3:171018565:C:T	G25E	0.984
3:170998080:A:C	F466L	0.983
3:170998080:A:T	F466L	0.983

dbSNP variants (sampled 300 via entrez): RS1000016245 (3:171019292 G>A), RS1000072650 (3:171008080 G>A), RS1000084900 (3:171006617 G>A), RS1000116119 (3:171015745 T>C), RS1000252316 (3:171015500 A>C), RS1000373429 (3:171002072 T>C), RS1000480235 (3:171009286 G>A), RS1000616993 (3:171020972 A>G,T), RS1000688851 (3:171008117 T>A), RS1000746659 (3:171009530 A>G), RS1000910062 (3:171027100 A>G,T), RS1001105694 (3:171027447 C>A,T), RS1001146839 (3:171026261 C>T), RS1001338096 (3:171021791 A>C), RS1001398123 (3:171027502 A>C)

Disease associations

OMIM: gene MIM:138160 | disease phenotypes: MIM:227810, MIM:125853, MIM:192500

GenCC curated gene-disease

Disease	Classification	Inheritance
glycogen storage disease due to GLUT2 deficiency	Definitive	Autosomal recessive
neonatal diabetes mellitus	Strong	Autosomal recessive
transient neonatal diabetes mellitus	Strong	Autosomal recessive
permanent neonatal diabetes mellitus	Strong	Autosomal recessive

Mondo (7): glycogen storage disease due to GLUT2 deficiency (MONDO:0009216), type 2 diabetes mellitus (MONDO:0005148), monogenic diabetes (MONDO:0015967), familial long QT syndrome (MONDO:0019171), neonatal diabetes mellitus (MONDO:0016391), transient neonatal diabetes mellitus (MONDO:0020525), permanent neonatal diabetes mellitus (MONDO:0100164)

Orphanet (4): Fanconi-Bickel syndrome (Orphanet:2088), Rare genetic diabetes mellitus (Orphanet:183625), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768)

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000124	Renal tubular dysfunction
HP:0000295	Doll-like facies
HP:0000819	Diabetes mellitus
HP:0000855	Insulin resistance
HP:0000938	Osteopenia
HP:0001263	Global developmental delay
HP:0001399	Hepatic failure
HP:0001402	Hepatocellular carcinoma
HP:0001406	Intrahepatic cholestasis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001941	Acidosis
HP:0001942	Metabolic acidosis
HP:0001947	Renal tubular acidosis
HP:0002024	Malabsorption
HP:0002148	Hypophosphatemia
HP:0002150	Hypercalciuria
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002748	Rickets
HP:0002749	Osteomalacia
HP:0002900	Hypokalemia
HP:0002904	Hyperbilirubinemia
HP:0002909	Generalized aminoaciduria
HP:0002919	Ketonuria

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000568_6	Fasting blood glucose	8.000000e-13
GCST001277_13	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-11
GCST001527_25	Fasting blood glucose (BMI interaction)	8.000000e-11
GCST003542_33	Night sleep phenotypes	1.000000e-06
GCST004206_11	Fasting plasma glucose	8.000000e-11
GCST004206_2	Fasting plasma glucose	1.000000e-11
GCST004522_1	Response to metformin in type 2 diabetes (HbA1c reduction)	7.000000e-14
GCST005180_4	Homeostasis model assessment of beta-cell function	5.000000e-06
GCST005186_25	Fasting blood glucose	2.000000e-09
GCST006001_20	Hemoglobin A1c levels	5.000000e-09
GCST006002_6	Blood sugar levels	4.000000e-18
GCST006613_13	Triglycerides	1.000000e-13
GCST007615_18	C-reactive protein levels	4.000000e-08
GCST007899_4	Fasting blood glucose	5.000000e-08
GCST007954_3	Glycated hemoglobin levels	1.000000e-11
GCST009379_141	Type 2 diabetes	5.000000e-21
GCST010118_28	Type 2 diabetes	1.000000e-11
GCST010244_289	Triglyceride levels	2.000000e-15
GCST010988_123	Adult body size	9.000000e-15
GCST011349_47	Gamma glutamyl transferase levels	4.000000e-10
GCST90011898_156	Alanine aminotransferase levels	2.000000e-09
GCST90013405_97	Liver enzyme levels (alanine transaminase)	2.000000e-11
GCST90013407_12	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-95

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004340	body mass index
EFO:0004541	HbA1c measurement
EFO:0004469	HOMA-B
EFO:0004468	glucose measurement
EFO:0004530	triglyceride measurement
EFO:0004458	C-reactive protein measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5873 (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: 74,559 (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
CHEMBL50	QUERCETIN	3	74,559

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs8192675	Efficacy	3	metformin	Diabetes Mellitus

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8192675	SLC2A2	3	0.00	1	metformin
rs1499821	SLC2A2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Class I transporters

ChEMBL bioactivities

94 potent at pChembl≥5 of 116 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.68	IC50	21	nM	CHEMBL3781913
7.22	IC50	60	nM	CHEMBL3781149
7.00	IC50	100	nM	CHEMBL3781331
6.66	IC50	220	nM	CHEMBL3780717
6.29	IC50	510	nM	CHEMBL3780372
6.22	IC50	600	nM	CHEMBL3780756
6.06	IC50	880	nM	CHEMBL3780470
6.05	IC50	900	nM	CHEMBL3780772
6.02	IC50	950	nM	CHEMBL3781835
6.00	IC50	1000	nM	CHEMBL3781347
5.96	IC50	1100	nM	CHEMBL3781548
5.95	IC50	1120	nM	CHEMBL3780459
5.92	IC50	1210	nM	CHEMBL3781994
5.92	IC50	1200	nM	CHEMBL3781654
5.92	IC50	1200	nM	CHEMBL3780235
5.87	IC50	1360	nM	CHEMBL3780764
5.85	IC50	1400	nM	CHEMBL3781308
5.83	IC50	1480	nM	CHEMBL3781827
5.77	IC50	1700	nM	CHEMBL3781183
5.70	IC50	2000	nM	CHEMBL3780527
5.68	IC50	2100	nM	CHEMBL3780729
5.67	IC50	2150	nM	CHEMBL5661921
5.60	IC50	2500	nM	CHEMBL3781633
5.58	IC50	2600	nM	CHEMBL3781625
5.55	IC50	2800	nM	CYTOCHALASIN B
5.48	IC50	3300	nM	CHEMBL3781384
5.46	IC50	3500	nM	CHEMBL3780785
5.41	IC50	3940	nM	CHEMBL5661909
5.36	IC50	4400	nM	CHEMBL3780845
5.30	IC50	5000	nM	CHEMBL3781757
5.25	IC50	5630	nM	CHEMBL5661924
5.22	IC50	5990	nM	CHEMBL3781094
5.22	IC50	6000	nM	CHEMBL3781797
5.16	IC50	7000	nM	CHEMBL3781535
5.15	IC50	7110	nM	CHEMBL5661942
5.10	IC50	8000	nM	CHEMBL3780349
5.07	IC50	8500	nM	CHEMBL5661925
5.06	IC50	8700	nM	CHEMBL3780534
5.03	IC50	9400	nM	BAY-876
5.03	IC50	9280	nM	CHEMBL5661833
5.00	IC50	1e+04	nM	CHEMBL3780043
5.00	IC50	1e+04	nM	CHEMBL1551510
5.00	IC50	1e+04	nM	CHEMBL4277734
5.00	IC50	1e+04	nM	CHEMBL4284767
5.00	IC50	1e+04	nM	CHEMBL4285795
5.00	IC50	1e+04	nM	CHEMBL4292886
5.00	IC50	1e+04	nM	CHEMBL4289272
5.00	IC50	1e+04	nM	CHEMBL4280482
5.00	IC50	1e+04	nM	CHEMBL4277326
5.00	IC50	1e+04	nM	CHEMBL4289936

PubChem BioAssay actives

41 with measured affinity, of 126 total; 41 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
4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0210	uM
2-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]phenol	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0600	uM
4-methoxy-3-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzamide	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1000	uM
3-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.2200	uM
4-[4-(4-methoxy-3-pyridinyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.5100	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[3,4-b]pyridine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.6000	uM
1-(5-fluoro-2-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.8800	uM
1-(3-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.9000	uM
4-[4-(3-methoxy-2-pyridinyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.9500	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(2-methylphenyl)pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.0000	uM
1-(2-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.1000	uM
4-[4-(2-fluorophenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.1200	uM
1-(2-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.2000	uM
4-[4-(2-fluoro-6-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.2000	uM
4-[4-(3-fluorophenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.2100	uM
4-[4-(2-methoxy-3-pyridinyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.3600	uM
4-[4-(2-methoxyphenyl)-3-methylpiperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.4000	uM
4-[4-(3-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.4800	uM
3-methoxy-4-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	1.7000	uM
1-cyclopentyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	2.0000	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(1-phenylethyl)pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	2.1000	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-8-fluoroquinoline-2,4-dicarboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	2.1500	uM
4-[4-(2-methoxyphenyl)-2-methylpiperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	2.5000	uM
1-(4-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	2.6000	uM
(1S,4E,6R,10R,12E,14S,15S,17S,18S,19S)-19-benzyl-6,15-dihydroxy-10,17-dimethyl-16-methylidene-2-oxa-20-azatricyclo[12.7.0.01,18]henicosa-4,12-diene-3,21-dione	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	2.8000	uM
7-[4-(2-methoxyphenyl)piperazin-1-yl]-3-phenyltriazolo[4,5-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	3.3000	uM
6-[4-(2-methoxyphenyl)piperazin-1-yl]-9-phenylpurine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	3.5000	uM
N-[1-[(4-fluorophenyl)methyl]-3,5-dimethylpyrazol-4-yl]-2-(furan-2-yl)-6,8-dimethylquinoline-4-carboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	3.9400	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-pyridin-4-ylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	4.4000	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[4,5-c]pyridine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	5.0000	uM
6-bromo-N-[1-[2-(4-fluorophenyl)ethyl]-3,5-dimethylpyrazol-4-yl]-2-(trifluoromethyl)quinoline-4-carboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	5.6300	uM
2-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	5.9900	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-pyridin-3-ylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	6.0000	uM
1-(3-fluoro-2-pyridinyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	7.0000	uM
6-bromo-N-[1-[1-(4-fluorophenyl)ethyl]-3,5-dimethylpyrazol-4-yl]-2-(trifluoromethyl)quinoline-4-carboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	7.1100	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-pyridin-2-ylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	8.0000	uM
6-bromo-N-[3,5-dimethyl-1-(oxan-4-ylmethyl)pyrazol-4-yl]-2-(trifluoromethyl)quinoline-4-carboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	8.5000	uM
4-[4-(4-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	8.7000	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-7-methoxyquinoline-2,4-dicarboxamide	2155043: Inhibition of human GLUT2 expressed in CHO cells assessed as reduction in fructose uptake by measuring decrease in ATP production incubated for 15 mins in presence of oxidative phosphorylation inhibitor rotenone by CellTiter-Glo Luminescent Cell Viability Assay	ic50	9.2800	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(3-methylphenyl)pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	10.0000	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(4-methylphenyl)pyrazolo[5,4-d]pyrimidine	1288119: Inhibition of human GLUT2 expressed in CHO cells assessed as ATP production co-incubated with 30 mM fructose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, decreases reaction, increases expression, decreases expression, increases reaction (+1 more)	7
Benzo(a)pyrene	decreases expression, affects methylation	6
Glucose	decreases expression, decreases reaction, increases transport, increases expression	4
Cyclosporine	decreases expression	4
Metformin	increases response to substance, decreases expression, decreases reaction, increases phosphorylation	3
Rifampin	decreases expression, increases reaction	3
Aflatoxin B1	decreases methylation, affects expression, decreases expression	3
arsenite	decreases expression, increases methylation	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression, increases abundance	2
sodium arsenite	decreases expression	2
Resveratrol	affects localization, affects reaction, decreases reaction, increases expression, increases reaction	2
Acetaminophen	decreases expression	2
Cadmium	affects cotreatment, increases abundance, affects binding, increases reaction, decreases reaction (+1 more)	2
Calcitriol	decreases expression	2
Endosulfan	affects cotreatment, decreases expression, increases reaction	2
Fructose	decreases reaction, increases transport	2
Quercetin	decreases activity, decreases expression	2
Oleic Acid	decreases reaction, increases expression, affects cotreatment, decreases expression	2
Palmitic Acid	affects cotreatment, increases abundance, increases expression, decreases expression	2
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide	decreases expression, decreases reaction	1
dicrotophos	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	decreases expression, increases abundance	1
bisphenol A	affects expression	1
tributyltin	increases expression	1
afimoxifene	decreases reaction, increases expression	1
hyperoside	increases expression	1
indirubin	decreases expression	1
benazol P	affects expression	1
5-iodotubercidin	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1045565	Binding	Inhibition of GLUT2-mediated [14C]D-glucose uptake in human MCF7 cells by liquid scintillation counting	Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. — Bioorg Med Chem
CHEMBL5209605	Functional	Inhibition of the Glucose Transporter (GLUT2, SLC2A2) as assessed by a FRET based flow cytometry assay using a genetically-encoded biosensor for measuring free glucose (FLII12Pglu-700uDelta6) in HEK293 JumpIN TRex SLC2A2 WT-OE cells (PubChe	Flow cytometry transport assay for SLC2A2 using HEK293 JumpIN TRex SLC2A2 WT-OE cells

Cellosaurus cell lines

8 cell lines: 4 induced pluripotent stem cell, 3 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4NT	QBRIi007-B	Induced pluripotent stem cell	Female
CVCL_A4NU	QBRIi007-C	Induced pluripotent stem cell	Female
CVCL_A8MY	QBRIi012-A	Induced pluripotent stem cell	Male
CVCL_D4T0	HuH7-SLC2A2-KO-c5	Cancer cell line	Male
CVCL_D4T1	HuH7-SLC2A2-KO-c7	Cancer cell line	Male
CVCL_HA59	BHK-PPI-C16-GCK-GLUT	Spontaneously immortalized cell line	Male
CVCL_HA61	HEP G2ins/g	Cancer cell line	Male
CVCL_YR07	QBRIi007-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes