SLC2A5

Summary

SLC2A5 (solute carrier family 2 member 5, HGNC:11010) is a protein-coding gene on chromosome 1p36.23, encoding Solute carrier family 2, facilitated glucose transporter member 5 (P22732). Functions as a fructose transporter that has only low activity with other monosaccharides.

The protein encoded by this gene is a fructose transporter responsible for fructose uptake by the small intestine. The encoded protein also is necessary for the increase in blood pressure due to high dietary fructose consumption.

Source: NCBI Gene 6518 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total
• Druggable target: yes
• MANE Select transcript: NM_003039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11010
Approved symbol	SLC2A5
Name	solute carrier family 2 member 5
Location	1p36.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142583
Ensembl biotype	protein_coding
OMIM	138230
Entrez	6518

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 retained_intron

ENST00000377414, ENST00000377424, ENST00000464985, ENST00000473209, ENST00000474145, ENST00000479813, ENST00000484798, ENST00000486632, ENST00000487492, ENST00000487835, ENST00000941832, ENST00000941833, ENST00000941834

RefSeq mRNA: 5 — MANE Select: NM_003039 NM_001135585, NM_001328619, NM_001328620, NM_001328621, NM_003039

CCDS: CCDS44054, CCDS99

Canonical transcript exons

ENST00000377424 — 12 exons

Exon	Start	End
ENSE00001598247	9039800	9039987
ENSE00001608607	9035106	9037789
ENSE00001707317	9040064	9040189
ENSE00001720327	9037897	9038024
ENSE00001796743	9039552	9039662
ENSE00001942467	9069504	9069635
ENSE00002752925	9058152	9058250
ENSE00002952224	9057448	9057608
ENSE00003547268	9038431	9038506
ENSE00003652705	9047610	9047734
ENSE00003680716	9038828	9038929
ENSE00003787605	9041785	9041937

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.04.

FANTOM5 (CAGE): breadth broad, TPM avg 7.3192 / max 429.4417, expressed in 563 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10191	3.0427	363
10190	2.2747	403
10192	1.0190	224
10188	0.5404	198
10189	0.1018	50
10193	0.0899	64
10201	0.0761	3
10187	0.0610	23
10198	0.0262	3
10194	0.0226	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.04	gold quality
duodenum	UBERON:0002114	95.78	gold quality
biceps brachii	UBERON:0001507	94.76	gold quality
adult organism	UBERON:0007023	94.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.76	gold quality
vastus lateralis	UBERON:0001379	92.67	silver quality
hindlimb stylopod muscle	UBERON:0004252	92.30	gold quality
left testis	UBERON:0004533	92.16	gold quality
quadriceps femoris	UBERON:0001377	91.57	silver quality
triceps brachii	UBERON:0001509	91.49	gold quality
jejunum	UBERON:0002115	90.87	gold quality
right testis	UBERON:0004534	90.87	gold quality
skeletal muscle tissue	UBERON:0001134	90.73	gold quality
bone marrow	UBERON:0002371	90.70	gold quality
bone marrow cell	CL:0002092	89.74	gold quality
testis	UBERON:0000473	89.62	gold quality
muscle organ	UBERON:0001630	89.59	gold quality
small intestine	UBERON:0002108	88.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.82	gold quality
gastrocnemius	UBERON:0001388	88.78	gold quality
muscle of leg	UBERON:0001383	88.73	gold quality
gluteal muscle	UBERON:0002000	88.41	gold quality
nephron tubule	UBERON:0001231	88.26	gold quality
deltoid	UBERON:0001476	86.70	gold quality
tendon of biceps brachii	UBERON:0008188	86.62	gold quality
trabecular bone tissue	UBERON:0002483	86.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.16	gold quality
muscle tissue	UBERON:0002385	85.17	gold quality
tibialis anterior	UBERON:0001385	84.55	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	43.34
E-ANND-3	yes	8.39
E-MTAB-9801	yes	3.64
E-GEOD-100618	no	906.27
E-MTAB-7303	no	9.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1, TCF3

miRNA regulators (miRDB)

30 targeting SLC2A5, 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-5692A	100.00	74.40	6850
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-6822-3P	96.60	66.06	680
HSA-MIR-345-5P	96.40	66.43	663
HSA-MIR-1245A	96.33	66.25	498
HSA-MIR-8079	96.33	66.11	484
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-4524B-3P	95.52	64.12	964

Literature-anchored findings (GeneRIF, showing 34)

• Fructose modulation of GLUT5 mRNA stability via cyclic AMP-signalling pathway and PABP (polyadenylated-binding protein)-interacting protein (Paip) 2. (PMID:12820898)
• 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)
• GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers (PMID:16803853)
• GLUT5 expression is dramatically increased in diabetic muscle and pioglitazone treatment reverses this overexpression. (PMID:17251278)
• These results suggest that inactivation of p44/42 MAPK enhances T(3)-induced GLUT5 gene expression in Caco-2 cells through increasing TRalpha-1 transactivity and binding activity to the GLUT5-TRE, probably due to de-phosphorylation of TRalpha-1. (PMID:17577579)
• De-phosphorylation of GR at Ser203 in nuclei associates with GR nuclear translocation and GLUT5 gene expression in Caco-2 cells. (PMID:18424253)
• These results suggest that the histone H3 di-methylation at lysine 9, as well as acetylation at lysine 9/14, may be indispensable for coordinated induction of the GLUT5 gene by p44/42 MAP kinase inhibition and the glucocorticoid hormone. (PMID:18439419)
• Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. (PMID:19091748)
• these results suggest that methylation of histone H3 at K4 and acetylation of histones H3 and H4 are involved in SLC2A5 gene induction associated with intestinal differentiation of Caco-2 cells. (PMID:20043883)
• A role for the GLUT5 isoform in fructose uptake that takes place in clear renal cell carcinoma cells and which subsequently leads to the malignant progression. (PMID:21165569)
• In high grade prostatic intraepithelial neoplasia, Glut-1 was immunohistochemically undetectable and Glut-5 localized to the apical portion of the plasma membrane of the hyper-proliferative cells (PMID:21938742)
• [(99m)Tc]GLA uptake is related to GLUT-5 transporter expression and transport (PMID:23084044)
• 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)
• SGLT1 and GLUT5 expression in the plasma membrane is regulated by TNFalpha, leading to alteration on sugar transport, suggesting that TNFalpha could be a physiological local regulator of nutrient absorption in response to an intestinal inflammatory status. (PMID:23910014)
• SLC2A5-inhibits the human normal adjacent lung adenocarcinoma cytoplasmic pro-B cell development mechanism network. (PMID:25326153)
• High expression of SLC2A5 in SUP-B15/R acute lymphoblastic leukemia cells leads to increased fructose absorption, and further activates PI3K/AKT pathway which cause the SUP-B15 cell resistance to imatinib. (PMID:28616912)
• identified amino acid residues of GLUT5 that define its substrate specificity for glucose transporter 5 (GLUT5)-mediated fructose transport. (PMID:29259131)
• fructose can be used by glioma cells, and restrict the fructose intake or targeting GLUT5 could be efficacious strategies in glioma. (PMID:29660339)
• Besides GLUT1, GLUT5 seems to be regulated under hypoxia. (PMID:29913554)
• It was found that SLC2A5, which encodes solute carrier family 2 member 5 (SLC2A5, previously termed GLUT5) facilitates cell fructose uptake and was up-regulated in Philadelphia chromosome-positive ALL. (PMID:30272826)
• An essential role for GLUT5-mediated fructose utilization in exacerbating the malignancy of clear cell renal cell carcinoma. (PMID:31102011)
• Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR. (PMID:31243309)
• The Solute Carrier Family 2 Genes Are Potential Prognostic Biomarkers in Acute Myeloid Leukemia. (PMID:31918632)
• GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling. (PMID:32051337)
• GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells. (PMID:32649737)
• S100P contributes to promoter demethylation and transcriptional activation of SLC2A5 to promote metastasis in colorectal cancer. (PMID:34188196)
• Identification of new GLUT2-selective inhibitors through in silico ligand screening and validation in eukaryotic expression systems. (PMID:34215797)
• SLC2A5 Correlated with Immune Infiltration: A Candidate Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma. (PMID:34604392)
• GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer. (PMID:35257833)
• Serum Iba-1, GLUT5, and TSPO in Patients With Diabetic Retinopathy: New Biomarkers for Early Retinal Neurovascular Alterations? A Pilot Study. (PMID:35285861)
• Gene variants of the SLC2A5 gene encoding GLUT5, the major fructose transporter, do not contribute to clinical presentation of acquired fructose malabsorption. (PMID:35387598)
• Obesity and overweight are linked to increased sodium-glucose cotransporter 1 and glucose transporter 5 levels in duodenum. (PMID:36746764)
• Fructose promotes angiogenesis by improving vascular endothelial cell function and upregulating VEGF expression in cancer cells. (PMID:37507736)
• GLUT5: structure, functions, diseases and potential applications. (PMID:37674366)

Cross-species orthologs

37 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc2a5	ENSDARG00000077875
mus_musculus	Slc2a5	ENSMUSG00000028976
rattus_norvegicus	Slc2a5	ENSRNOG00000017693
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	nebu	FBGN0036316
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	CG33281	FBGN0053281
drosophila_melanogaster	CG33282	FBGN0053282
caenorhabditis_elegans		WBGENE00010684
caenorhabditis_elegans		WBGENE00010811
caenorhabditis_elegans		WBGENE00012536
caenorhabditis_elegans		WBGENE00013074
caenorhabditis_elegans		WBGENE00016431
caenorhabditis_elegans		WBGENE00017382
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), 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 5 — P22732 (reviewed: P22732)

Alternative names: Fructose transporter, Glucose transporter type 5, small intestine

All UniProt accessions (6): P22732, A0A140VJK5, K7EIT1, K7EJR1, K7EJZ0, K7EQI3

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a fructose transporter that has only low activity with other monosaccharides. Can mediate the uptake of 2-deoxyglucose, but with low efficiency. Essential for fructose uptake in the small intestine. Plays a role in the regulation of salt uptake and blood pressure in response to dietary fructose. Required for the development of high blood pressure in response to high dietary fructose intake.

Subcellular location. Apical cell membrane. Cell membrane. Sarcolemma.

Tissue specificity. Detected in skeletal muscle, and in jejunum brush border membrane and basolateral membrane (at protein level). Expressed in small intestine, and at much lower levels in kidney, skeletal muscle, and adipose tissue.

Activity regulation. The uptake of 2-deoxyglucose is inhibited by cytochalasin B. Fructose transport is inhibited by the flavonoids epigallocatechin gallate and apigenin but not quercetin.

Induction. By forskolin in Caco-2 cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P22732-1	1	yes
P22732-2	2

RefSeq proteins (5): NP_001129057, NP_001315548, NP_001315549, NP_001315550, NP_003030* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002442	Fru_transpt_5	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), 1 shown:

• D-fructose(out) = D-fructose(in) (RHEA:60372)

UniProt features (37 total): topological domain 13, transmembrane region 12, binding site 6, chain 1, modified residue 1, glycosylation site 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22732-F1	90.35	0.73

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): 32; 167; 288; 296–298; 387; 419–420

Post-translational modifications (1): 1

Glycosylation sites (1): 51

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8981373	Intestinal hexose absorption

MSigDB gene sets: 184 (showing top): GOBP_DIGESTION, GOBP_CARBOHYDRATE_TRANSPORT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_BLOOD_PRESSURE, MODULE_169, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, SHIPP_DLBCL_CURED_VS_FATAL_DN, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, SHEPARD_BMYB_MORPHOLINO_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, CEBALLOS_TARGETS_OF_TP53_AND_MYC_DN

GO Biological Process (11): regulation of systemic arterial blood pressure mediated by a chemical signal (GO:0003044), carbohydrate metabolic process (GO:0005975), response to fructose (GO:0009750), fructose transmembrane transport (GO:0015755), obsolete D-glucose import (GO:0046323), dehydroascorbic acid transport (GO:0070837), cellular response to fructose stimulus (GO:0071332), intestinal hexose absorption (GO:0106001), D-glucose transmembrane transport (GO:1904659), fructose import across plasma membrane (GO:1990539), transmembrane transport (GO:0055085)

GO Molecular Function (5): fructose transmembrane transporter activity (GO:0005353), D-glucose transmembrane transporter activity (GO:0055056), fructose binding (GO:0070061), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), specific granule membrane (GO:0035579), sarcolemma (GO:0042383), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Intestinal absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
hexose transmembrane transport	2
fructose transmembrane transport	2
hexose transmembrane transporter activity	2
sperm flagellum	2
regulation of systemic arterial blood pressure	1
primary metabolic process	1
response to hexose	1
vitamin transport	1
response to fructose	1
cellular response to hexose stimulus	1
intestinal absorption	1
hexose import across plasma membrane	1
transport	1
cellular process	1
monosaccharide binding	1
binding	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
secretory granule membrane	1
specific granule	1
plasma membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC2A5	CA6	P23280	863
SLC2A5	SLC5A1	P13866	851
SLC2A5	KHK	P50053	792
SLC2A5	CA3	P07451	764
SLC2A5	ENO1	P06733	737
SLC2A5	SLC22A12	Q96S37	716
SLC2A5	SLC15A1	P46059	645
SLC2A5	TAS1R3	Q7RTX0	618
SLC2A5	G6PC3	Q9BUM1	605
SLC2A5	G6PC2	Q9NQR9	602
SLC2A5	CA2	P00918	589
SLC2A5	CA1	P00915	588
SLC2A5	INS	P01308	560
SLC2A5	SLC5A11	Q8WWX8	556
SLC2A5	SLC5A10	A0PJK1	552

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SLC2A5	ARL13B	psi-mi:“MI:0915”(physical association)	0.670
SLC2A5	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	EVI2B	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	FCRL3	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	ATP6V0B	psi-mi:“MI:0915”(physical association)	0.560
MGST3	SLC2A5	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	TMEM130	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
PAGE1	SLC2A5	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
COMT	SLC2A5	psi-mi:“MI:0915”(physical association)	0.560
SLC2A5	RBFOX3	psi-mi:“MI:0914”(association)	0.530
SLC2A5	LPGAT1	psi-mi:“MI:0914”(association)	0.530
RPSA	SLC2A5	psi-mi:“MI:0915”(physical association)	0.370
CCL5	SLC2A5	psi-mi:“MI:0915”(physical association)	0.370
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC2A5	TMEM237	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	EVI2B	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	FCRL3	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	ATP6V0B	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	MGST3	psi-mi:“MI:0915”(physical association)	0.000
TMEM130	SLC2A5	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	SCN3B	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
SLC2A5	PAGE1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (146): RBFOX3 (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), LMBRD2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), FITM2 (Affinity Capture-MS), OSBPL6 (Affinity Capture-MS), KIAA0368 (Affinity Capture-MS), SLC2A5 (Two-hybrid), SLC2A5 (Two-hybrid), SLC2A5 (Two-hybrid), SLC2A5 (Two-hybrid), MGST3 (Two-hybrid), TMEM237 (Two-hybrid)

ESM2 similar proteins: A0A3Q2IDB4, A0A8B7HA97, A4ZYQ5, A6NK97, G1SZD9, O35956, O57379, O88909, P22732, P23945, P43427, Q0IHM1, Q2KIV1, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R9C4, Q5RC45, Q5RCH6, Q5RET7, Q63ZE4, Q66J52, Q6DFR1, Q6NUB3, Q6NYN7, Q6PXP3, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q863Y9, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48, Q8N4F4, Q8R0S9

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

1 interactions.

A	Effect	B	Mechanism
SLC2A5	“up-regulates quantity”	D-fructofuranose	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	17

Top pathogenic / likely-pathogenic (0)

SpliceAI

1817 predictions. Top by Δscore:

Variant	Effect	Δscore
1:9037785:CCCTC:C	acceptor_gain	1.0000
1:9037786:CCTCC:C	acceptor_gain	1.0000
1:9037787:CTC:C	acceptor_gain	1.0000
1:9037788:TCC:T	acceptor_loss	1.0000
1:9037790:C:CC	acceptor_gain	1.0000
1:9037893:TCAC:T	donor_loss	1.0000
1:9037894:CACCT:C	donor_loss	1.0000
1:9038023:ACC:A	acceptor_loss	1.0000
1:9038025:C:CC	acceptor_gain	1.0000
1:9038427:GTA:G	donor_loss	1.0000
1:9038428:TAC:T	donor_loss	1.0000
1:9038429:A:AC	donor_gain	1.0000
1:9038429:ACTG:A	donor_loss	1.0000
1:9038430:C:CG	donor_gain	1.0000
1:9038430:CT:C	donor_gain	1.0000
1:9038430:CTGG:C	donor_gain	1.0000
1:9038430:CTGGG:C	donor_gain	1.0000
1:9038447:T:TA	donor_gain	1.0000
1:9038506:CCT:C	acceptor_loss	1.0000
1:9038507:C:CC	acceptor_gain	1.0000
1:9039547:CTCA:C	donor_loss	1.0000
1:9039548:TCA:T	donor_loss	1.0000
1:9039549:CACGG:C	donor_loss	1.0000
1:9039550:A:AC	donor_gain	1.0000
1:9039550:ACGG:A	donor_gain	1.0000
1:9039550:ACGGC:A	donor_loss	1.0000
1:9039551:C:CG	donor_gain	1.0000
1:9039551:CG:C	donor_gain	1.0000
1:9039551:CGG:C	donor_gain	1.0000
1:9039551:CGGC:C	donor_gain	1.0000

AlphaMissense

3234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:9040185:C:A	W192C	0.998
1:9040185:C:G	W192C	0.998
1:9040187:A:G	W192R	0.998
1:9040187:A:T	W192R	0.998
1:9037766:G:C	F442L	0.997
1:9037766:G:T	F442L	0.997
1:9037768:A:G	F442L	0.997
1:9037757:G:C	F445L	0.996
1:9037757:G:T	F445L	0.996
1:9037759:A:G	F445L	0.996
1:9037909:G:C	F430L	0.996
1:9037909:G:T	F430L	0.996
1:9037911:A:G	F430L	0.996
1:9038470:A:G	C379R	0.996
1:9039810:C:T	G292D	0.996
1:9040113:G:C	S216R	0.996
1:9040113:G:T	S216R	0.996
1:9040115:T:G	S216R	0.996
1:9047621:C:T	G136E	0.996
1:9047633:C:G	R132T	0.996
1:9039803:G:C	N294K	0.995
1:9039803:G:T	N294K	0.995
1:9039810:C:A	G292V	0.995
1:9047622:C:G	G136R	0.995
1:9047622:C:T	G136R	0.995
1:9037941:A:G	W420R	0.994
1:9037941:A:T	W420R	0.994
1:9038448:C:T	G386E	0.994
1:9038477:G:C	S376R	0.994
1:9038477:G:T	S376R	0.994

dbSNP variants (sampled 300 via entrez): RS1000060362 (1:9094325 A>T), RS1000065863 (1:9087123 G>A,T), RS1000108968 (1:9045591 A>G), RS1000110529 (1:9073940 C>A), RS1000143957 (1:9043745 G>A), RS1000150069 (1:9046948 T>C), RS1000190721 (1:9085966 C>T), RS1000274118 (1:9080836 T>G), RS1000299379 (1:9079930 T>A), RS1000315751 (1:9091881 C>T), RS1000351226 (1:9068583 C>G,T), RS1000364781 (1:9043477 G>A,T), RS1000367518 (1:9050469 CA>C,CAA), RS1000425834 (1:9074553 A>G), RS1000524854 (1:9074085 AT>A,ATT)

Disease associations

OMIM: gene MIM:138230 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5875 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Class II transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Fructose	increases stability, increases transport, increases expression, increases reaction, affects binding (+1 more)	5
Tretinoin	affects cotreatment, increases expression	5
bisphenol A	increases expression, affects methylation, affects cotreatment, increases methylation	3
Glucose	affects binding, increases transport, increases expression, increases reaction	3
bisphenol S	decreases expression	2
Arsenic Trioxide	affects cotreatment, increases expression	2
Cyclic AMP	affects expression, increases abundance, increases stability	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Nickel	decreases reaction, affects expression, increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
testosterone undecanoate	affects cotreatment, increases expression	1
trichostatin A	affects expression, decreases reaction	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
monomethylarsonic acid	decreases expression	1
arsenic acid	decreases expression, increases abundance	1
hydroquinone	decreases expression	1
tamibarotene	increases expression	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	increases expression, increases stability, decreases reaction	1
monomethylarsonous acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
dimethylmonothioarsinic acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Pioglitazone	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Mirtazapine	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1045567	Binding	Inhibition of GLUT5-mediated [14C]D-fructose 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4VT	LS180-SLC2A5-KO-c6	Cancer cell line	Female
CVCL_D4VU	LS180-SLC2A5-KO-c7	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea