SLC2A3

Summary

SLC2A3 (solute carrier family 2 member 3, HGNC:11007) is a protein-coding gene on chromosome 12p13.31, encoding Solute carrier family 2, facilitated glucose transporter member 3 (P11169). Facilitative glucose transporter.

Enables D-glucose binding activity; dehydroascorbic acid transmembrane transporter activity; and hexose transmembrane transporter activity. Involved in D-glucose import across plasma membrane; galactose transmembrane transport; and transport across blood-brain barrier. Located in aggresome and plasma membrane. Biomarker of Alzheimer’s disease; acanthosis nigricans; diabetes mellitus; and type 2 diabetes mellitus.

Source: NCBI Gene 6515 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Huntington disease (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 79 total
• Phenotypes (HPO): 52
• Druggable target: yes
• MANE Select transcript: NM_006931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11007
Approved symbol	SLC2A3
Name	solute carrier family 2 member 3
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000059804
Ensembl biotype	protein_coding
OMIM	138170
Entrez	6515

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 retained_intron, 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000075120, ENST00000469295, ENST00000476634, ENST00000479059, ENST00000486749, ENST00000490763, ENST00000495813, ENST00000541671, ENST00000543435, ENST00000544291, ENST00000544936, ENST00000631571, ENST00000707174, ENST00000707175, ENST00000715759, ENST00000926562, ENST00000926563

RefSeq mRNA: 1 — MANE Select: NM_006931 NM_006931

CCDS: CCDS8586

Canonical transcript exons

ENST00000075120 — 10 exons

Exon	Start	End
ENSE00001659755	7929684	7929871
ENSE00001801301	7930480	7930642
ENSE00001922435	7919230	7921631
ENSE00003497022	7933810	7933902
ENSE00003506596	7925844	7925948
ENSE00003532473	7936020	7936187
ENSE00003575499	7924410	7924511
ENSE00003600832	7931245	7931485
ENSE00003643202	7932987	7933147
ENSE00003684296	7922821	7923024

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.4519 / max 2453.1434, expressed in 1602 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129303	68.4519	1602

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.02	gold quality
vena cava	UBERON:0004087	98.92	gold quality
pericardium	UBERON:0002407	98.87	gold quality
saphenous vein	UBERON:0007318	98.74	gold quality
blood	UBERON:0000178	98.49	gold quality
monocyte	CL:0000576	97.67	gold quality
gall bladder	UBERON:0002110	97.65	gold quality
omental fat pad	UBERON:0010414	97.46	gold quality
mononuclear cell	CL:0000842	97.44	gold quality
peritoneum	UBERON:0002358	97.40	gold quality
leukocyte	CL:0000738	97.31	gold quality
bone marrow	UBERON:0002371	97.07	gold quality
colonic epithelium	UBERON:0000397	96.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.82	gold quality
trigeminal ganglion	UBERON:0001675	96.72	gold quality
bone marrow cell	CL:0002092	96.46	gold quality
upper lobe of left lung	UBERON:0008952	96.46	gold quality
dorsal root ganglion	UBERON:0000044	96.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.37	gold quality
upper lobe of lung	UBERON:0008948	96.09	gold quality
periodontal ligament	UBERON:0008266	95.92	gold quality
nerve	UBERON:0001021	95.74	gold quality
tibial nerve	UBERON:0001323	95.74	gold quality
right lung	UBERON:0002167	95.72	gold quality
mucosa of stomach	UBERON:0001199	94.85	gold quality
granulocyte	CL:0000094	94.81	gold quality
olfactory bulb	UBERON:0002264	94.48	gold quality
primary visual cortex	UBERON:0002436	94.13	gold quality
middle frontal gyrus	UBERON:0002702	94.10	gold quality
stromal cell of endometrium	CL:0002255	94.08	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	17686.65
E-GEOD-36552	yes	3546.49
E-GEOD-131882	yes	3111.70
E-ANND-2	yes	2867.78
E-CURD-97	yes	2777.59
E-GEOD-106540	yes	2394.44
E-GEOD-75688	yes	1832.22
E-GEOD-135922	yes	1821.53
E-ENAD-20	yes	1523.82
E-MTAB-8205	yes	456.94
E-MTAB-10287	yes	70.99
E-CURD-88	yes	52.85
E-CURD-122	yes	49.81
E-HCAD-1	yes	40.92
E-CURD-112	yes	24.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, CTNNB1, HIF1A, HMGA1, MECP2, MYOG, NR3C1, POU5F1, SP1, SP3, TFCP2, YBX1, ZBTB7A, ZEB1

miRNA regulators (miRDB)

130 targeting SLC2A3, 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-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977

Literature-anchored findings (GeneRIF, showing 40)

• GLUT3 is expressed by normal articular chondrocytes. (PMID:11991658)
• observed differential response of individual isoforms GLUT1, GLUT3, & GLUT4 in neutrophils and granulocytes to hypoglycemia may represent a mechanism to protect the cells from the stress of glucose deprivation (PMID:12064911)
• glucose transporter 1 and 3 in the placenta (PMID:12112827)
• Restricted to regenerating muscle fibres and nerves in adult human muscle. GLUT3 may be important for glucose supply in fetal muscle fibres and regenerating adult muscle fibres. (PMID:12397394)
• Embedded in microvillous (maternal-facing) and basal (fetal-facing) membranes of syncytiotrophoblast, main placental barrier layer. (review) (PMID:12583599)
• Differentiation of THP-1 monocytes into macrophages was associated with marked induction of GLUT 3 and GLUT 5 protein expression, and high levels of GLUT 1, GLUT 3, and GLUT 5 were maintained after transformation to foam cells. (PMID:14757434)
• in platelets glucose transport through GLUT3 is regulated by changes in surface expression and affinity modulation, which are both under control of PKB (PMID:16049004)
• We present an alternative hypothesis centring on presumed deficits in membrane bound glucose transporter proteins GLUT 1 and GLUT 3, either in absolute numbers or functional capacity. (PMID:16125330)
• This review presents a model incorporating hypoxia responsive facilitative GLUT1 and GLUT3 as putative components of the glucose sensing apparatus in chondrocytes (PMID:16136514)
• During trophoblast hypoxia glucose transporters (GLUT1/3) are upregulated via HIF-1 alpha pathway. (PMID:17442736)
• Regulation of GLUT3 and glucose uptake by the cAMP signallling pathway in the breast cancer cell line ZR-75 is reported. (PMID:17559076)
• Findings suggest that characteristic differences in the patterns of glucose uptake can exist according to the histological type and that GLUT1, GLUT3 and GLUT4 could be related to tumor angiogenesis in epithelial ovarian carcinoma. (PMID:17611657)
• IGF-1 plays a role in maintaining muscle GLUT3 expression and basal glucose uptake via the transcriptional factor Sp1. (PMID:17920708)
• GLUT3 expression was studied in normal and degenerate intervertebral discs. (PMID:18172662)
• In hyperthyroidism: 1) basal abundance of GLUT3 and GLUT4 on the plasma membrane is increased and 2) the sensitivity of the recruitment of GLUT3 and GLUT4 transporters on the plasma membrane in response to IGF-I is increased (PMID:18299470)
• GLUT-3 gene expression level was high in head and neck carcinoma (HNCs), and its expression was associated with an increased incidence of lymph node metastasis of HNCs. (PMID:18401196)
• differential expression of Glut-3 by benign and malignant melanocytic lesions (PMID:18764953)
• Sertoli cells express GLUT1 and GLUT3 throughout pubertal development. (PMID:18802725)
• the activation of AMP-activated protein kinase and its regulation of cell surface GLUT3 expression is critical in mediating neuronal tolerance to excitotoxicity (PMID:19261894)
• study to evaluate the expression of glucose transporters (Gluts) 1 and 3 in Hodgkin and nonHodgkin lymphoma and to assess the association between their expression and the tumor intensity on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PMID:19536037)
• The expression pattern of GLUT3 is reported in newly diagnosed esophageal adenocarcinoma by means of immunohistochemistry. (PMID:19554504)
• The neuronal glucose transporter 3 was decreased to a bigger extent in Type 2 Diabetes Mellitus brain than in Alzheimer’s disease brain. (PMID:19659459)
• At physiological glucose, GLUT1 and GLUT3 are the predominant active isoforms in HeLa cells and rat hepatocarcinoma AS-30D tumor cells, respectively. (PMID:19681047)
• expression of HIF-1alpha and GLUT-3 in glioma was correlated significantly with tumors’ pathological grade, which can be taken as a pair of useful markers for predicting the biological behavior of glioma (PMID:19782666)
• Results suggest a possible transregulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated mismatch negativity in passive listening tasks. (PMID:19786962)
• GLUT1 and GLUT3 protein expression are indicators of poor prognosis outcome in oral squamous cell carcinoma, probably due to the enhanced glycolytic metabolism of more aggressive neoplastic cells. (PMID:20428049)
• In pluripotent stem cells and in human cancer disease, podocalyxin may function in part to regulate and maintain the cell surface expression of the glucose-3-transporter. (PMID:20599725)
• DNA-damaging agents reduce GLUT3 expression in cancer cells through activation of the MEK-ERK pathway independently of p53, leading to cell death or apoptosis (PMID:20870738)
• 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)
• GLUT3 is present in the syncytial microvillous membrane early in gestation and decreases thereafter, supporting the idea that GLUT3 is of greater importance for glucose uptake early in gestation. (PMID:22000473)
• human islets from T1D predominantly express GLUT1 and, to a much lesser extent, GLUT3 on their surface instead of GLUT2. (PMID:22069254)
• Human glucose transporter type 3 (GLUT3)in the brain exhibits water channel properties (PMID:22113212)
• in placenta, CRH produced locally regulates GLUT1 and GLUT3 expression, CRHR1 and CRHR2-mediated differential regulation of GLUT1 and GLUT3 expression (PMID:22234467)
• miR-195-5p is a novel and also the first identified miRNA that targets GLUT3, and the aberrant decreased expression of miR-195-5p and consequent GLUT3 up-regulation may contribute to bladder carcinogenesis. (PMID:22265971)
• High GLUT3 is associated with endometrial and breast cancers. (PMID:22270867)
• We clarified that early hypoxia-responsive genes are functionally associated with glycolysis, including SLC2A3. (PMID:22645302)
• assessed how triiodothyronine (T(3)) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T(3) and insulin action. (PMID:22663547)
• Data show that elevated CAV1 upregulates glucose uptake and ATP production through HMGA1-mediated GLUT3 transcription, suggesting that CAV1 may render tumor cells growth advantages by enhancing aerobic glycolysis. (PMID:22706202)
• hypoxia-induced increases in glucose uptake through GLUT3 are important for lipid synthesis in macrophages, and may contribute to foam cell formation in hypoxic regions of atherosclerotic lesions. (PMID:22876317)
• GLUT3 shows increasing promoter methylation across gestation. (PMID:22901689)

Cross-species orthologs

46 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000001937
danio_rerio	slc2a3b	ENSDARG00000037861
danio_rerio	slc2a11l	ENSDARG00000062873
danio_rerio	slc2a9l1	ENSDARG00000070672
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): SLC2A9 (ENSG00000109667), SLC2A1 (ENSG00000117394), SLC2A11 (ENSG00000133460), SLC2A8 (ENSG00000136856), SLC2A5 (ENSG00000142583), SLC2A12 (ENSG00000146411), SLC2A13 (ENSG00000151229), SLC2A6 (ENSG00000160326), SLC2A2 (ENSG00000163581), SLC2A14 (ENSG00000173262), SLC2A4 (ENSG00000181856), SLC2A7 (ENSG00000197241), SLC2A10 (ENSG00000197496)

Protein

Protein identifiers

Solute carrier family 2, facilitated glucose transporter member 3 — P11169 (reviewed: P11169)

Alternative names: Glucose transporter type 3, brain

All UniProt accessions (3): P11169, F5GYR5, F5GYX0

UniProt curated annotations — full annotation on UniProt →

Function. Facilitative glucose transporter. Can also mediate the uptake of various other monosaccharides across the cell membrane. Mediates the uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and probably also dehydroascorbate. Does not mediate fructose transport. Required for mesendoderm differentiation.

Subunit / interactions. Interacts with SMIM43; the interaction may promote SLC2A3-mediated glucose transport to meet the energy needs of mesendoderm differentiation.

Subcellular location. Cell membrane. Perikaryon. Cell projection.

Tissue specificity. Highly expressed in brain. Expressed in many tissues.

Activity regulation. Deoxyglucose transport is inhibited by D-glucose, D-galactose and maltose. Galactose transport is inhibited by D-glucose and maltose.

Domain organisation. Transport is mediated via a series of conformation changes, switching between a conformation where the substrate-binding cavity is accessible from the outside, and a another conformation where it is accessible from the cytoplasm.

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

RefSeq proteins (1): NP_008862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002945	Glc_transpt_3	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), 2 shown:

• D-galactose(in) = D-galactose(out) (RHEA:34915)
• D-glucose(out) = D-glucose(in) (RHEA:60376)

UniProt features (74 total): helix 25, topological domain 13, transmembrane region 12, turn 7, binding site 6, modified residue 4, strand 2, chain 1, region of interest 1, glycosylation site 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4ZW9	X-RAY DIFFRACTION	1.5
7SPT	X-RAY DIFFRACTION	2.1
7CRZ	X-RAY DIFFRACTION	2.3
7SPS	X-RAY DIFFRACTION	2.3
4ZWB	X-RAY DIFFRACTION	2.4
4ZWC	X-RAY DIFFRACTION	2.6
5C65	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11169-F1	90.44	0.75

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): 159; 280–281; 286; 315; 378; 386

Post-translational modifications (4): 232, 475, 485, 492

Glycosylation sites (1): 43

Mutagenesis-validated functional residues (1):

Position	Phenotype
277–279	confers moderate fructose transport activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-196836	Vitamin C (ascorbate) metabolism
R-HSA-6798695	Neutrophil degranulation
R-HSA-9022699	MECP2 regulates neuronal receptors and channels

MSigDB gene sets: 583 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_CARBOHYDRATE_TRANSPORT, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, AMIT_EGF_RESPONSE_60_HELA, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MENSE_HYPOXIA_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN

GO Biological Process (9): carbohydrate metabolic process (GO:0005975), galactose transmembrane transport (GO:0015757), L-ascorbic acid metabolic process (GO:0019852), obsolete D-glucose import (GO:0046323), dehydroascorbic acid transport (GO:0070837), D-glucose import across plasma membrane (GO:0098708), transport across blood-brain barrier (GO:0150104), D-glucose transmembrane transport (GO:1904659), transmembrane transport (GO:0055085)

GO Molecular Function (6): galactose transmembrane transporter activity (GO:0005354), D-glucose binding (GO:0005536), dehydroascorbic acid transmembrane transporter activity (GO:0033300), D-glucose transmembrane transporter activity (GO:0055056), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (10): plasma membrane (GO:0005886), membrane (GO:0016020), aggresome (GO:0016235), secretory granule membrane (GO:0030667), specific granule membrane (GO:0035579), cell projection (GO:0042995), perikaryon (GO:0043204), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Metabolism of water-soluble vitamins and cofactors	1
Innate Immune System	1
Transcriptional Regulation by MECP2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
secretory granule membrane	3
hexose transmembrane transport	2
hexose transmembrane transporter activity	2
tertiary granule	2
primary metabolic process	1
monosaccharide metabolic process	1
carboxylic acid metabolic process	1
lactone metabolic process	1
vitamin transport	1
hexose import across plasma membrane	1
D-glucose transmembrane transport	1
vascular transport	1
transport	1
cellular process	1
galactose transmembrane transport	1
monosaccharide binding	1
dehydroascorbic acid transport	1
vitamin transmembrane transporter activity	1
binding	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
inclusion body	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
specific granule	1
neuronal cell body	1
extracellular vesicle	1
ficolin-1-rich granule	1

Protein interactions and networks

STRING

2488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC2A3	HK1	P19367	730
SLC2A3	SLC16A3	O15427	706
SLC2A3	LDHA	P00338	703
SLC2A3	HIF1A	Q16665	703
SLC2A3	HK2	P52789	692
SLC2A3	SLC16A4	O15374	680
SLC2A3	PKM	P14618	680
SLC2A3	INS	P01308	673
SLC2A3	CLEC4A	Q9UMR7	668
SLC2A3	PFKM	P08237	632
SLC2A3	STOM	P27105	615
SLC2A3	SLC5A1	P13866	614
SLC2A3	PFKFB3	Q16875	611
SLC2A3	PDK1	Q15118	610
SLC2A3	SLC23A2	Q9UGH3	607

IntAct

132 interactions, top by confidence:

A	B	Type	Score
SLC2A3	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
SLC2A14	SLC2A3	psi-mi:“MI:0914”(association)	0.530
SLC2A3	LGALS3	psi-mi:“MI:0914”(association)	0.530
MAST2	SLC2A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
RHPN1	SLC2A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	SLC2A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC2A3	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (51): SLC2A3 (Two-hybrid), SLC2A3 (Affinity Capture-MS), SLC2A3 (Two-hybrid), SLC2A3 (Two-hybrid), SLC2A3 (Proximity Label-MS), SLC2A3 (Proximity Label-MS), SLC2A3 (Proximity Label-MS), SLC2A3 (Proximity Label-MS), CLPP (Co-fractionation), HSPA4 (Co-fractionation), PAICS (Co-fractionation), RCN2 (Co-fractionation), CREB3L1 (Two-hybrid), SLC2A3 (Proximity Label-MS), ALDH1A1 (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: A0A0H2VG78, A0A1D8PH98, A9ZSY3, B4HNS1, B4QBN3, C0SPB2, F1R0H0, J9VHZ4, O04249, O23492, O34718, O52733, O62786, O62787, O65413, P0AE24, P0AE25, P0AEP1, P0AEP2, P0AGF4, P0AGF5, P11166, P11167, P11169, P12336, P13355, P14246, P15686, P15729, P17809, P23586, P27674, P30605, P30606, P32037, P39924, P45598, P46333, P46896, P47185

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
HMGA1	“up-regulates quantity by expression”	SLC2A3	“transcriptional regulation”
“HIF-1 complex”	“up-regulates quantity by expression”	SLC2A3	“transcriptional regulation”
SLC2A3	“up-regulates quantity”	α-D-glucose	relocalization
SLC2A3	“up-regulates quantity”	glucose	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	40.9×	7e-12
Dopamine Neurotransmitter Release Cycle	5	40.0×	4e-06
Long-term potentiation	5	38.4×	4e-06
Neurexins and neuroligins	10	31.8×	5e-11
Protein-protein interactions at synapses	6	25.7×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	68.4×	7e-14
receptor clustering	7	51.4×	2e-08
protein localization to synapse	5	45.1×	6e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.0×	2e-06
cell-cell adhesion	11	13.1×	1e-07
regulation of small GTPase mediated signal transduction	5	8.5×	7e-03
chemical synaptic transmission	9	8.2×	1e-04
protein-containing complex assembly	6	8.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7921627:TAGTG:T	acceptor_gain	1.0000
12:7921628:AGTG:A	acceptor_gain	1.0000
12:7921629:GTG:G	acceptor_gain	1.0000
12:7921630:TG:T	acceptor_gain	1.0000
12:7921632:C:CC	acceptor_gain	1.0000
12:7922815:ACTT:A	donor_loss	1.0000
12:7922816:CTT:C	donor_loss	1.0000
12:7922817:TTA:T	donor_loss	1.0000
12:7922818:T:TG	donor_loss	1.0000
12:7922819:A:AC	donor_gain	1.0000
12:7922819:A:T	donor_loss	1.0000
12:7922819:ACAG:A	donor_gain	1.0000
12:7922820:C:CT	donor_gain	1.0000
12:7922820:CA:C	donor_gain	1.0000
12:7922820:CAG:C	donor_gain	1.0000
12:7922820:CAGC:C	donor_gain	1.0000
12:7922820:CAGCA:C	donor_gain	1.0000
12:7923021:TATC:T	acceptor_gain	1.0000
12:7923021:TATCC:T	acceptor_loss	1.0000
12:7923023:TC:T	acceptor_gain	1.0000
12:7923024:CC:C	acceptor_gain	1.0000
12:7923024:CCTGT:C	acceptor_loss	1.0000
12:7923025:C:CA	acceptor_loss	1.0000
12:7923025:C:CC	acceptor_gain	1.0000
12:7924509:TAG:T	acceptor_gain	1.0000
12:7925842:A:AC	donor_gain	1.0000
12:7925843:C:CC	donor_gain	1.0000
12:7925945:ACAC:A	acceptor_gain	1.0000
12:7925946:CAC:C	acceptor_gain	1.0000
12:7925946:CACC:C	acceptor_gain	1.0000

AlphaMissense

3238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7922866:G:C	N409K	0.999
12:7922866:G:T	N409K	0.999
12:7922949:C:G	G382R	0.999
12:7922954:C:T	G380E	0.999
12:7922955:C:G	G380R	0.999
12:7922955:C:T	G380R	0.999
12:7922962:A:C	F377L	0.999
12:7922962:A:T	F377L	0.999
12:7922964:A:G	F377L	0.999
12:7929694:C:T	G284E	0.999
12:7929695:C:A	G284W	0.999
12:7931261:C:T	G165E	0.999
12:7931262:C:G	G165R	0.999
12:7931262:C:T	G165R	0.999
12:7933844:C:T	G25D	0.999
12:7921608:A:C	F432L	0.998
12:7921608:A:T	F432L	0.998
12:7921610:A:G	F432L	0.998
12:7922833:G:C	F420L	0.998
12:7922833:G:T	F420L	0.998
12:7922834:A:C	F420C	0.998
12:7922835:A:G	F420L	0.998
12:7922844:C:G	G417R	0.998
12:7922844:C:T	G417R	0.998
12:7922854:G:C	N413K	0.998
12:7922854:G:T	N413K	0.998
12:7922914:G:C	F393L	0.998
12:7922914:G:T	F393L	0.998
12:7922916:A:G	F393L	0.998
12:7922918:A:G	L392P	0.998

dbSNP variants (sampled 300 via entrez): RS1000150317 (12:7935407 G>A,T), RS1000203427 (12:7932562 GAAT>G), RS1000220385 (12:7925648 T>A), RS1000276943 (12:7932248 T>A), RS1000789801 (12:7927410 C>T), RS1000827837 (12:7938130 T>C), RS1000871332 (12:7932261 C>T), RS1000885341 (12:7928047 G>A,C), RS1000928349 (12:7932013 T>G), RS1001222185 (12:7927192 G>A), RS1001268401 (12:7928380 C>A), RS1001603833 (12:7929301 G>GGGCTACCTTGTATTT), RS1001617884 (12:7927804 C>G,T), RS1001745106 (12:7932811 T>C), RS1001824801 (12:7933752 C>G)

Disease associations

OMIM: gene MIM:138170 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Huntington disease	Supportive	Autosomal dominant

Mondo (1): Huntington disease (MONDO:0007739)

Orphanet (0):

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000496	Abnormality of eye movement
HP:0000713	Agitation
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000734	Disinhibition
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000746	Delusion
HP:0001250	Seizure
HP:0001262	Excessive daytime somnolence
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001347	Hyperreflexia
HP:0001824	Weight loss
HP:0002059	Cerebral atrophy
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002072	Chorea
HP:0002141	Gait imbalance
HP:0002169	Clonus
HP:0002300	Mutism
HP:0002312	Clumsiness
HP:0002340	Caudate atrophy
HP:0002354	Memory impairment
HP:0002375	Hypokinesia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005959_2	Waist-to-hip ratio adjusted for BMI x sex interaction	9.000000e-07
GCST009439_5	Age-related cognitive decline (language) (slope of z-scores)	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006816	Huntington Disease	C10.228.140.079.545; C10.228.140.380.278; C10.228.662.262.249.750; C10.574.500.497; C16.320.400.430; F03.615.250.400; F03.615.400.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5215 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Class I transporters

ChEMBL bioactivities

141 potent at pChembl≥5 of 158 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	IC50	8	nM	CHEMBL3781913
8.00	IC50	10	nM	CHEMBL3780239
7.92	IC50	12	nM	CHEMBL4645691
7.58	IC50	26	nM	CHEMBL4647311
7.48	IC50	33	nM	CHEMBL4634839
7.46	IC50	35	nM	CHEMBL5661838
7.43	IC50	37	nM	CHEMBL3781331
7.40	IC50	40	nM	CHEMBL3780972
7.40	IC50	40	nM	CHEMBL3781548
7.34	IC50	46	nM	CHEMBL3781151
7.33	IC50	47	nM	CHEMBL4634011
7.30	IC50	50	nM	CHEMBL3780144
7.24	IC50	58	nM	CHEMBL4633651
7.22	IC50	60	nM	CHEMBL3781149
7.22	IC50	60	nM	CHEMBL3780372
7.19	IC50	64	nM	CHEMBL3780785
7.17	IC50	68	nM	CHEMBL4638234
7.16	IC50	69	nM	CHEMBL3780717
7.16	IC50	70	nM	CHEMBL3781835
7.07	IC50	86	nM	CHEMBL5661939
7.05	IC50	90	nM	CHEMBL3780460
7.02	IC50	96	nM	CHEMBL3780043
7.01	IC50	97	nM	CHEMBL4648466
6.96	IC50	110	nM	CHEMBL3780235
6.96	IC50	110	nM	CHEMBL5661873
6.92	IC50	120	nM	CHEMBL3781308
6.92	IC50	120	nM	CHEMBL3781741
6.92	IC50	120	nM	CHEMBL3780527
6.92	IC50	121	nM	CHEMBL4637134
6.92	IC50	120	nM	CYTOCHALASIN B
6.86	IC50	138	nM	CHEMBL4635564
6.81	IC50	155	nM	CHEMBL4634012
6.80	IC50	160	nM	CHEMBL4635844
6.77	IC50	170	nM	CHEMBL3781183
6.77	IC50	170	nM	CHEMBL3780772
6.77	IC50	170	nM	CHEMBL3781625
6.76	IC50	175	nM	CHEMBL4638542
6.75	IC50	179	nM	CHEMBL4647401
6.70	IC50	200	nM	CHEMBL3781194
6.68	IC50	211	nM	CHEMBL4645036
6.64	IC50	230	nM	CHEMBL5661843
6.63	IC50	232	nM	CHEMBL4649311
6.62	IC50	238	nM	CHEMBL4649021
6.62	IC50	238	nM	CHEMBL4642809
6.60	IC50	250	nM	CHEMBL3781157
6.60	IC50	250	nM	CHEMBL3781347
6.56	IC50	275	nM	CHEMBL4642046
6.54	IC50	287	nM	CHEMBL4632395
6.54	IC50	290	nM	CHEMBL5661849
6.53	IC50	298	nM	CHEMBL4632920

PubChem BioAssay actives

135 with measured affinity, of 163 total; 50 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	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0080	uM
4-[4-(5-fluoro-2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0100	uM
N-(2-methylbutan-2-yl)-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0120	uM
N-tert-butyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0260	uM
N-pentan-3-yl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0330	uM
4-N-[1-[(4-cyanophenyl)methyl]-3-methylpyrazol-4-yl]-7-fluoroquinoline-2,4-dicarboxamide	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.0350	uM
4-methoxy-3-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzamide	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0370	uM
1-(2-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0400	uM
4-[4-(4-fluoro-2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0400	uM
1-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0460	uM
N-cyclopentyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0470	uM
4-methoxy-3-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0500	uM
N-tert-butyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0580	uM
4-[4-(4-methoxy-3-pyridinyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0600	uM
2-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]phenol	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0600	uM
6-[4-(2-methoxyphenyl)piperazin-1-yl]-9-phenylpurine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0640	uM
N-cyclobutyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0680	uM
3-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0690	uM
4-[4-(3-methoxy-2-pyridinyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0700	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-5-methylquinoline-2,4-dicarboxamide	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.0860	uM
1-(3,5-difluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0900	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(3-methylphenyl)pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.0960	uM
N-propan-2-yl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.0970	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-6-methoxyquinoline-2,4-dicarboxamide	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.1100	uM
1-(2-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1100	uM
1-cyclopentyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1200	uM
4-[4-(2-methoxyphenyl)-3-methylpiperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1200	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	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.1200	uM
1-(3-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1200	uM
N-pentan-3-yl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1210	uM
N-cyclopentyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1380	uM
N-tert-butyl-2-[3-[6-(oxolan-3-yl)-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1550	uM
2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]-N-(2,2,2-trifluoroethyl)acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1600	uM
1-(3-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1700	uM
1-(4-methoxyphenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1700	uM
3-methoxy-4-[4-(1-phenylpyrazolo[5,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.1700	uM
N-tert-butyl-2-[3-[6-(2-methoxyethyl)-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1750	uM
2-[3-[6-cyclobutyl-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]-N-(1-methylcyclopropyl)acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.1790	uM
4-[4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrazolo[5,4-d]pyrimidin-1-yl]benzonitrile	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.2000	uM
2-[3-[6-cyclopropyl-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]-N-(1-methylcyclopropyl)acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2110	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-5-fluoroquinoline-2,4-dicarboxamide	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.2300	uM
N-tert-butyl-2-[3-[6-(1-fluoropropan-2-yl)-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2320	uM
N-cyclopropyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2380	uM
2-[3-[6-cyclobutyl-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]-N-propan-2-ylacetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2380	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-(2-methylphenyl)pyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.2500	uM
4-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenylpyrazolo[5,4-d]pyrimidine	1288120: Inhibition of human GLUT3 expressed in GLUT1 knock-out DLD1 cells assessed as ATP production co-incubated with 300 mM glucose for 16 hrs by CellTiter-Glo assay in presence of oxidative phosphorylation inhibitor rotenone	ic50	0.2500	uM
N-tert-butyl-2-[3-[6-(1-methoxypropan-2-yl)-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2750	uM
N-tert-butyl-2-[3-[6-cyclobutyl-4-[4-(1H-pyrazol-4-yl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2870	uM
4-N-[1-[(4-cyanophenyl)methyl]-5-methyl-3-(trifluoromethyl)pyrazol-4-yl]-6-fluoroquinoline-2,4-dicarboxamide	2155044: Inhibition of human GLUT3 expressed in human GLUT1-/- DLD-1 cells assessed as reduction in glucose 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	0.2900	uM
N-propyl-2-[3-[4-[4-(1H-pyrazol-4-yl)anilino]-5,7-dihydrofuro[3,4-d]pyrimidin-2-yl]phenoxy]acetamide	1648687: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay	ic50	0.2980	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases response to substance, affects expression, affects reaction, affects cotreatment, decreases expression (+4 more)	7
Oxygen	affects cotreatment, decreases expression, affects expression, affects reaction, increases expression (+1 more)	6
Valproic Acid	affects cotreatment, increases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression, affects expression	4
Benzo(a)pyrene	decreases expression, affects methylation	4
Cadmium Chloride	decreases expression, increases expression, affects cotreatment	4
bisphenol A	affects expression, decreases methylation, increases expression	3
Amiodarone	decreases expression	3
Amitriptyline	decreases expression	3
Estradiol	affects cotreatment, decreases expression	3
Tamoxifen	affects expression, decreases expression	3
Tetrachlorodibenzodioxin	decreases expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
lead acetate	decreases expression, increases abundance, affects reaction, affects cotreatment	2
cobaltous chloride	increases expression	2
nickel sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
epigallocatechin gallate	decreases reaction, increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic Trioxide	increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Caffeine	affects phosphorylation, increases expression	2
Clomipramine	decreases expression	2
Dinitrochlorobenzene	decreases expression, increases expression	2

ChEMBL screening assays

11 unique, capped per target: 10 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061374	Binding	Inhibition of GLUT3 mediated [3H]-2-DG uptake in human LNCAP cells at 5 uM after 30 mins by scintillation counting	Development of a novel class of glucose transporter inhibitors. — J Med Chem
CHEMBL5209606	Functional	Inhibition of the Glucose Transporter (GLUT3, SLC2A3) as assessed by a FRET based flow cytometry assay using a genetically-encoded biosensor for measuring free glucose (FLII12Pglu-700uDelta6) in HEK293 JumpIN TRex SLC2A3 WT-OE cells (PubChe	Flow cytometry transport assay for SLC2A3 using HEK293 JumpIN TRex SLC2A3 WT-OE cells

Cellosaurus cell lines

15 cell lines: 9 induced pluripotent stem cell, 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0P9	UKWMPi007-A	Induced pluripotent stem cell	Male
CVCL_B0PA	UKWMPi007-B	Induced pluripotent stem cell	Male
CVCL_B0PB	UKWMPi008-A	Induced pluripotent stem cell	Female
CVCL_B0PC	UKWMPi008-B	Induced pluripotent stem cell	Female
CVCL_B0PD	UKWMPi011-A	Induced pluripotent stem cell	Female
CVCL_B0PE	UKWMPi011-B	Induced pluripotent stem cell	Female
CVCL_B0PF	UKWMPi012-A	Induced pluripotent stem cell	Male
CVCL_B0PG	UKWMPi012-B	Induced pluripotent stem cell	Male
CVCL_C7DL	Abcam A-549 SLC2A3 KO	Cancer cell line	Male
CVCL_C7EC	Abcam HCT 116 SLC2A3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00652457	PHASE4	COMPLETED	Study of Memantine to Treat Huntington’s Disease
NCT01834911	PHASE4	COMPLETED	Effect of Tetrabenazine on Stroop Interference in HD
NCT02509793	PHASE4	UNKNOWN	A Pilot Study Assessing Impulsivity in Patients With Huntington’s Disease on Xenazine (Tetrabenazine)
NCT07601516	PHASE4	COMPLETED	Real World Effectiveness and Safety of Deutetrabenazine in Adult Chinese Patients With Huntington’s Disease (HD) Chorea in China
NCT00146211	PHASE3	COMPLETED	TREND-HD - A Trial of Ethyl-EPA (Miraxion™) in Treating Mild to Moderate Huntington’s Disease
NCT00219804	PHASE3	COMPLETED	Efficacy and Safety of Tetrabenazine in Chorea
NCT00277602	PHASE3	COMPLETED	Riluzole in Huntington’s Disease
NCT00608881	PHASE3	TERMINATED	Coenzyme Q10 in Huntington’s Disease (HD)
NCT00632645	PHASE3	COMPLETED	Neuroleptic and Huntington Disease Comparison of : Olanzapine, la Tetrabenazine and Tiapride
NCT00665223	PHASE3	COMPLETED	A Study of Treatment With Pridopidine (ACR16) in Participants With Huntington’s Disease
NCT00712426	PHASE3	TERMINATED	Creatine Safety, Tolerability, & Efficacy in Huntington’s Disease (CREST-E)
NCT00920946	PHASE3	COMPLETED	A Safety and Efficacy Study of Dimebon in Patients With Huntington Disease
NCT01085266	PHASE3	TERMINATED	An Extension of the HORIZON Protocol Evaluating the Safety of Dimebon (Latrepirdine) in Subjects With Huntington Disease
NCT03842969	PHASE3	COMPLETED	An Open-Label Extension Study to Evaluate Long-Term Safety and Tolerability of RO7234292 (RG6042) in Huntington’s Disease Participants Who Participated in Prior Roche and Genentech Sponsored Studies
NCT03854019	PHASE3	COMPLETED	Evaluating the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington’s Disease
NCT04556656	PHASE3	COMPLETED	PRidopidine’s Outcome On Function in Huntington Disease, PROOF- HD
NCT04826692	PHASE3	COMPLETED	TEsting METformin Against Cognitive Decline in HD
NCT05655520	PHASE3	TERMINATED	A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Huntington’s Disease
NCT06097780	PHASE3	UNKNOWN	Efficacy and Safety of NestaCell® in Huntington’s Disease
NCT07326709	PHASE3	RECRUITING	A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington’s Disease
NCT07609108	PHASE3	NOT_YET_RECRUITING	PRidopidine Phase 3 Study to Establish Clinical Impact and Safety in Huntington’s Disease
NCT00001930	PHASE2	COMPLETED	Treatment of Huntington’s Chorea With Amantadine
NCT00095355	PHASE2	COMPLETED	Effects of Lithium and Divalproex’on Brain-Derived Neurotrophic Factor in Huntington’s Disease
NCT00190450	PHASE2	COMPLETED	MIG-HD: Multicentric Intracerebral Grafting in Huntington’s Disease
NCT00212316	PHASE2	COMPLETED	Safety and Tolerability Study of Phenylbutyrate in Huntington’s Disease (PHEND-HD)
NCT00271596	PHASE2	COMPLETED	Citalopram to Enhance Cognition in HD
NCT00368849	PHASE2	COMPLETED	Atomoxetine and Huntington’s Disease
NCT00497159	PHASE2	COMPLETED	A Study of the Novel Drug Dimebon in Patients With Huntington’s Disease
NCT00592995	PHASE2	COMPLETED	Creatine Safety and Tolerability in Premanifest HD: PRECREST
NCT00724048	PHASE2	COMPLETED	A Study of Pridopidine (ACR16) for the Treatment of Participants With Huntington’s Disease
NCT00920699	PHASE2	COMPLETED	Study in PRE-manifest Huntington’s Disease of Coenzyme Q10 (UbiquinonE) Leading to Preventive Trials (PREQUEL)
NCT01019473	PHASE2	TERMINATED	Efficacy, Safety and Tolerability of AFQ056 in Patients With Huntington’s Disease in Reducing Chorea
NCT01306929	PHASE2	COMPLETED	Open-label Extension Study of Pridopidine (ACR16) in the Symptomatic Treatment of Huntington Disease
NCT01357681	PHASE2	COMPLETED	Effects of EGCG (Epigallocatechin Gallate) in Huntington’s Disease (ETON-Study)
NCT01411150	PHASE2	COMPLETED	Premanifest Huntington’s Disease: Creatine Safety & Tolerability Extension Study
NCT01411163	PHASE2	COMPLETED	Premanifest Huntington’s Disease Extension Study II: Creatine Safety & Tolerability
NCT01412151	PHASE2	COMPLETED	Creatine Safety & Tolerability in Huntington’s Disease
NCT01458470	PHASE2	COMPLETED	A Trial of Memantine as Symptomatic Treatment for Early Huntington Disease
NCT01502046	PHASE2	COMPLETED	Neuroprotection by Cannabinoids in Huntington’s Disease
NCT01521585	PHASE2	COMPLETED	A Phase II Safety and Tolerability Study With SEN0014196