SLC2A9

Summary

SLC2A9 (solute carrier family 2 member 9, HGNC:13446) is a protein-coding gene on chromosome 4p16.1, encoding Solute carrier family 2, facilitated glucose transporter member 9 (Q9NRM0). High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules.

This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 56606 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypouricemia, renal, 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 86
• Clinical variants (ClinVar): 309 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13446
Approved symbol	SLC2A9
Name	solute carrier family 2 member 9
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	Glut9, GLUTX, URATv1
Ensembl gene	ENSG00000109667
Ensembl biotype	protein_coding
OMIM	606142
Entrez	56606

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 9 protein_coding_CDS_not_defined

ENST00000264784, ENST00000309065, ENST00000481042, ENST00000503280, ENST00000503803, ENST00000505104, ENST00000505506, ENST00000506583, ENST00000506839, ENST00000508585, ENST00000509214, ENST00000512342, ENST00000513129, ENST00000851828, ENST00000851829, ENST00000851830, ENST00000851831, ENST00000851832, ENST00000967831

RefSeq mRNA: 2 — MANE Select: NM_020041 NM_001001290, NM_020041

CCDS: CCDS3406, CCDS3407

Canonical transcript exons

ENST00000264784 — 12 exons

Exon	Start	End
ENSE00000816684	10021280	10021497
ENSE00001130793	9826224	9826600
ENSE00003509341	10018975	10019073
ENSE00003531457	9920385	9920572
ENSE00003554277	9996781	9996941
ENSE00003580347	9887567	9887642
ENSE00003580780	9985669	9985793
ENSE00003598177	9941913	9942045
ENSE00003656836	9908235	9908345
ENSE00003691289	9890610	9890711
ENSE00003694285	9834881	9835008
ENSE00003786892	9980592	9980737

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 98.17.

FANTOM5 (CAGE): breadth broad, TPM avg 4.1361 / max 167.2536, expressed in 667 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51340	1.6580	392
51341	1.2774	431
51345	0.6091	39
51339	0.4816	180
51342	0.0600	10
51344	0.0499	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.17	gold quality
monocyte	CL:0000576	87.02	gold quality
mononuclear cell	CL:0000842	86.58	gold quality
adult mammalian kidney	UBERON:0000082	86.55	gold quality
leukocyte	CL:0000738	86.21	gold quality
right lobe of liver	UBERON:0001114	85.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.63	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.05	gold quality
metanephros cortex	UBERON:0010533	82.17	gold quality
pancreatic ductal cell	CL:0002079	82.07	silver quality
kidney	UBERON:0002113	81.58	gold quality
granulocyte	CL:0000094	80.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.37	gold quality
lower esophagus	UBERON:0013473	80.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.19	gold quality
liver	UBERON:0002107	80.00	gold quality
cortex of kidney	UBERON:0001225	79.90	gold quality
right lung	UBERON:0002167	79.85	gold quality
saliva-secreting gland	UBERON:0001044	79.48	gold quality
esophagus	UBERON:0001043	79.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.90	gold quality
minor salivary gland	UBERON:0001830	78.87	gold quality
esophagus mucosa	UBERON:0002469	78.35	gold quality
nephron tubule	UBERON:0001231	77.27	gold quality
mouth mucosa	UBERON:0003729	77.10	gold quality
parotid gland	UBERON:0001831	76.67	gold quality
right atrium auricular region	UBERON:0006631	76.19	gold quality
upper lobe of left lung	UBERON:0008952	76.05	gold quality
lower esophagus mucosa	UBERON:0035834	75.96	gold quality
popliteal artery	UBERON:0002250	75.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	1520.52
E-ANND-3	yes	18.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting SLC2A9, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-3074-5P	98.82	66.56	1414

Literature-anchored findings (GeneRIF, showing 40)

• GLUT9 is expressed by normal articular chondrocytes. (PMID:11991658)
• alternative splicing alters trafficking (PMID:14739288)
• These results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. (PMID:17997608)
• GLUT9 expression was studied in normal and degenerate intervertebral discs. (PMID:18172662)
• GLUT1 and 9 are preferentially localized to the plasma membrane and thus can account for the transport activity. (PMID:18177733)
• Single nucleotide polymorphism in SLC2A9 is associated with Gout (PMID:18327256)
• SLC2A9 variants were associated with low fractional excretion of uric acid and/or gout (PMID:18327257)
• common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on coronary artery disease or myocardial infarct in a German population (PMID:18398472)
• Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and body mass index. (PMID:18487473)
• Serum uric acid levels and renal uric acid excretion have been found to be modulated by genetic polymorphisms in SLC2A9, a fructose transporter, which can influence the risk for gout by affecting renal urate reabsorption. (PMID:18606621)
• The in vivo role of GLUT9 is supported by the fact that a renal hypouricemia patient without any mutations in SLC22A12 was found to have a missense mutation in SLC2A9, which reduced urate transport activity in vitro. (PMID:18701466)
• GLUT9, which is expressed in the kidney, may be a novel regulator of uric acid elimination and that a common nonsynonymous variant in this gene contributes to abnormalities in uric acid homeostasis and gout. (PMID:18759275)
• Study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. (PMID:18842065)
• Mutations in SLC2A9 cause renal hypouricemia. (PMID:19026395)
• the apical expression of SLC2A9 secretes urate back into the urine in exchange for lumenal glucose and SLC2A9 could be the primary route for urate movement–review (PMID:19593129)
• In the SardiNIA study, a GWAS found several SNPs in the GLUT9 gene to be associated with levels of Uric Acid. (PMID:19679263)
• Non-synonymous SNP rs3733591 variant within the SLC2A9 gene from two geographically diverse populations(Han Chinese subjects and Solomon Islanders) served as an important genetic checkpoint for tophaceous gout and increased uric acid levels. (PMID:19723617)
• GLUT9, which seems to be both a fructose and a uric acid transporter, plays an important role in these conditions associated with hyperuricemia–REVIEW (PMID:19797240)
• Studies confirm the expression of GLUT9a and GLUT9b in murine and human beta-cells (PMID:19808778)
• There is a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set and association of SLC2A9 with gout in samples of Maori and Pacific Island ancestry. (PMID:19877038)
• polymorphisms in SLC2A9 and ABCG2 influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease (PMID:19890391)
• Homozygous loss-of-function mutations of SLC2A9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. (PMID:19926891)
• Genetic variants within SLC2A9,ABCG2 and SLC17A3 are associated with uric acid levels (PMID:20053405)
• Three single nucleotide polymorphisms from the SLC2A9 gene were correlated with dietary habits and uric acid. (PMID:20162744)
• Development of nephrolithiasis may be associated with SLC2A9 gene. (PMID:20162745)
• Significant associations were detected with SLC2A9 and a general memory factor and other individual cognitive ability tests. (PMID:20197412)
• Results showed that the association between single nucleotide polymorphism in GLUT9 and the development of gout was replicated in Japanese men. (PMID:20413573)
• renal urate transporters SLC2A9 and ABCG2: The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry (PMID:20472486)
• Results implicate genetic variation in SLC2A9 in influencing levels of serum urate over a broad range of values in a large Mauritian family cohort. (PMID:20588307)
• Data suggest that SLC2A9 genetic variants influence age of onset of Parkinson’s disease (PMID:20589538)
• replicated the associations of the SLC2A9 and ABCG2 polymorphisms with serum UA and clarified the prognostic significance of the SLC22A12, SLC2A9 and ABCG2 genotypes for the development of hyperuricemia (PMID:20714133)
• expression of glucose transporter type 9(GLUT9) isoforms is significantly increased in placental tissue from diabetic pregnancies and may play a role in the fetal pathophysiology associated with diabetes-complicated pregnancies (PMID:20926839)
• the polymorphism rs6855911 in SLC2A9 may have a role in hyperuricemia among the Chinese male Han population (PMID:20972595)
• There is a association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families. (PMID:21186168)
• a novel homozygous insertion in exon 3 of the SLC2A9 gene caused renal hypouricemia (PMID:21256783)
• Four variants of the gene SLC2A9 achieved genome-wide significance for association with serum uric acid. (PMID:21294900)
• the first report to estimate the impact of SLC2A9 rs11722228 on serum uric acid levels. (PMID:21511506)
• GLUT9, unlike URAT1, may play a specific role in exercise-induced PRES. (PMID:21536615)
• The SNP rs1014290 within the SLC2A9 gene is associated with type 2 DM in Han Chinese. (PMID:21584282)
• For SLC2A9 we were unable to replicate associations of rs3733591 with gout in Eastern Polynesian, Western Polynesian and Caucasian samples. (PMID:21658257)

Cross-species orthologs

45 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000117001
mus_musculus	Slc2a9	ENSMUSG00000005107
rattus_norvegicus	Slc2a9	ENSRNOG00000005302
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), 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 9 — Q9NRM0 (reviewed: Q9NRM0)

Alternative names: Glucose transporter type 9, Urate transporter

All UniProt accessions (2): Q9NRM0, D6REK5

UniProt curated annotations — full annotation on UniProt →

Function. High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules. May have a residual high-affinity, low-capacity glucose and fructose transporter activity. Transports urate at rates 45- to 60-fold faster than glucose. Does not transport galactose. May mediate small uptake of adenine but not of other nucleobases.

Subcellular location. Cell membrane. Basolateral cell membrane Cell membrane. Apical cell membrane. Basolateral cell membrane.

Tissue specificity. Most strongly expressed in basolateral membranes of proximal renal tubular cells, liver and placenta. Also detected in lung, blood leukocytes, heart skeletal muscle and chondrocytes from articular cartilage. Detected in kidney membrane (at protein level). Only detected in the apical membranes of polarized renal tubular cells and placenta. Detected in kidney membrane (at protein level).

Disease relevance. Hypouricemia renal 2 (RHUC2) [MIM:612076] A disorder characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells, and high urinary urate excretion. Patients often appear asymptomatic, but may be subject to exercise-induced acute renal failure, chronic renal dysfunction and nephrolithiasis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Extracellular glucose and urate accelerate urate efflux. Intracellular urate, glucose and fructose accelerate urate influx. No effect of extracellular urate, glucose or fructose on urate efflux. Intracellular urate and fructose slightly accelerate urate influx.

Polymorphism. Genetic variations in SLC2A9 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 2 (UAQTL2) [MIM:612076] with pronounced sex-specific effects. The proportion of the variance of serum uric acid concentrations explained by genotypes is about 1.2% in men and 6% in women, and the percentage accounted for by expression levels is 3.5% in men and 15% in women. Excess serum accumulation of uric acid can lead to the development of gout.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRM0-1	1, SLC2A9-L, SLC2A9a	yes
Q9NRM0-2	2, GLUT9deltaN, SLC2A9-S, SLC2A9b

RefSeq proteins (2): NP_001001290, NP_064425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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:

• urate(out) = urate(in) (RHEA:60368)

UniProt features (60 total): sequence variant 19, topological domain 13, transmembrane region 12, mutagenesis site 9, region of interest 2, modified residue 2, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8ZXN	ELECTRON MICROSCOPY	3.06
9VPG	ELECTRON MICROSCOPY	3.14
8Y66	ELECTRON MICROSCOPY	3.28
9CAX	ELECTRON MICROSCOPY	3.37
8ZXM	ELECTRON MICROSCOPY	3.39
8Y65	ELECTRON MICROSCOPY	3.51
9CBB	ELECTRON MICROSCOPY	4.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRM0-F1	82.79	0.53

Functional residue map

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

Post-translational modifications (2): 9, 515

Glycosylation sites (1): 90

Mutagenesis-validated functional residues (9):

Position	Phenotype
157	no effect on fructose transport. increased urate binding affinity and decreased urate transport capacity.
210	decreased urate uptake. decreased vmax for urate transport. has no effect on glucose transport.
210	decreased fructose transport. higher affinity and lower transport capacity for urate.
326	no effect on urate and fructose transport.
330	increased fructose transport. highly reduced urate transport.
332	increased fructose binding affinity and decreased fructose transport capacity.
427	no effect on fructose transport. higher affinity and lower transport capacity for urate.
480	no effect on urate and fructose transport.
488	no effect on fructose transport. highly reduced urate transport.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-189200	Cellular hexose transport
R-HSA-5619047	Defective SLC2A9 causes hypouricemia renal 2 (RHUC2)

MSigDB gene sets: 182 (showing top): GOBP_CARBOHYDRATE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_D_GLUCOSE_IMPORT, GOBP_ORGANIC_ANION_TRANSPORT, chr4p16, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_VITAMIN_TRANSPORT, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOCC_APICAL_PLASMA_MEMBRANE, RYTTCCTG_ETS2_B, GOBP_URATE_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_95, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (9): hexose transmembrane transport (GO:0008645), urate transport (GO:0015747), fructose transmembrane transport (GO:0015755), obsolete D-glucose import (GO:0046323), urate metabolic process (GO:0046415), dehydroascorbic acid transport (GO:0070837), D-glucose transmembrane transport (GO:1904659), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (7): carbohydrate:proton symporter activity (GO:0005351), fructose transmembrane transporter activity (GO:0005353), urate transmembrane transporter activity (GO:0015143), transmembrane transporter activity (GO:0022857), D-glucose transmembrane transporter activity (GO:0055056), protein binding (GO:0005515), hexose transmembrane transporter activity (GO:0015149)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
SLC transporter disorders	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hexose transmembrane transport	3
hexose transmembrane transporter activity	2
plasma membrane region	2
monosaccharide transmembrane transport	1
nitrogen compound transport	1
small molecule metabolic process	1
purine-containing compound metabolic process	1
vitamin transport	1
transport	1
cellular process	1
monoatomic cation transmembrane transport	1
carbohydrate:monoatomic cation symporter activity	1
solute:proton symporter activity	1
fructose transmembrane transport	1
urate transport	1
salt transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
binding	1
monosaccharide transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
basal plasma membrane	1
apical part of cell	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC2A9	SLC22A12	Q96S37	996
SLC2A9	SLC22A11	Q9NSA0	976
SLC2A9	SLC17A1	Q14916	876
SLC2A9	ABCG2	Q9UNQ0	874
SLC2A9	PDZK1	Q5T2W1	866
SLC2A9	SLC17A3	O00476	819
SLC2A9	SLC22A6	Q4U2R8	780
SLC2A9	SLC22A8	Q8TCC7	776
SLC2A9	SLC22A13	Q9Y226	773
SLC2A9	SLC5A8	Q8N695	741
SLC2A9	SLC16A9	Q7RTY1	730
SLC2A9	SLC5A12	Q1EHB4	724
SLC2A9	SLC22A9	Q8IVM8	723
SLC2A9	XDH	P47989	686
SLC2A9	ALDH16A1	Q8IZ83	624

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ITM2B	SLC2A9	psi-mi:“MI:0915”(physical association)	0.400
SLC2A9	HIP1R	psi-mi:“MI:0914”(association)	0.350
RAI2	CRYGS	psi-mi:“MI:0914”(association)	0.350
ZNF136	STAT4	psi-mi:“MI:0914”(association)	0.350
SLC2A9	EXOC5	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): TKT (Co-fractionation), GK (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), UQCRH (Affinity Capture-MS), ORMDL1 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), HIP1R (Affinity Capture-MS), ZWILCH (Affinity Capture-MS), MFSD9 (Affinity Capture-MS), TVP23C (Affinity Capture-MS), GBF1 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), TUBGCP4 (Affinity Capture-MS), IPO11 (Affinity Capture-MS)

ESM2 similar proteins: A1A5C7, A6H7A0, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, O43688, O62772, O75147, P0CK96, P35438, P35439, P52875, P57791, Q05586, Q28D01, Q2KJ29, Q3KNV8, Q3SZQ2, Q3UHH2, Q4L208, Q4V899, Q5R1P0, Q5R890, Q5SP67, Q5ZJ75, Q7TPB4, Q86YN1, Q8BTQ0, Q8C6G8, Q8C811, Q8R4D1, Q8VDI9, Q8VE98, Q90812, Q9BWV1, Q9D9E0, Q9H6U8, Q9H7D7

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	122
Likely benign	68
Benign	59

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1027407	NM_020041.3(SLC2A9):c.593G>A (p.Arg198His)	Pathogenic
2113538	NM_020041.3(SLC2A9):c.372dup (p.Thr125fs)	Pathogenic
217422	NC_000004.12:g.(?9826223)(9908346_9920384)del	Pathogenic
2810823	NM_020041.3(SLC2A9):c.1287del (p.Pro430fs)	Pathogenic
3246754	NC_000004.11:g.(?9943517)(9943689_?)del	Pathogenic
4598	NM_020041.3(SLC2A9):c.1235C>G (p.Pro412Arg)	Pathogenic
4698261	NM_020041.3(SLC2A9):c.944G>A (p.Trp315Ter)	Pathogenic
685255	GRCh37/hg19 4p16.1(chr4:9927512-9954773)x1	Pathogenic
687332	GRCh37/hg19 4p16.1(chr4:9794001-9833187)x1	Pathogenic
1879601	NM_020041.3(SLC2A9):c.1035del (p.Ala346fs)	Likely pathogenic
217421	NM_020041.3(SLC2A9):c.374C>T (p.Thr125Met)	Likely pathogenic
2628597	NM_020041.3(SLC2A9):c.681+1G>T	Likely pathogenic
3359196	NM_020041.3(SLC2A9):c.570T>G (p.Ser190Arg)	Likely pathogenic
3359197	NM_020041.3(SLC2A9):c.1202C>T (p.Thr401Met)	Likely pathogenic
3767964	NM_020041.3(SLC2A9):c.1557dup (p.Ala520fs)	Likely pathogenic
4697034	NM_020041.3(SLC2A9):c.1292-2A>T	Likely pathogenic
4731956	NM_020041.3(SLC2A9):c.1114-2A>C	Likely pathogenic
830032	NM_020041.3(SLC2A9):c.1343C>T (p.Pro448Leu)	Likely pathogenic

SpliceAI

2630 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9908233:A:AC	donor_gain	1.0000
4:9908234:C:CC	donor_gain	1.0000
4:9920383:A:AC	donor_gain	1.0000
4:9920383:ACTG:A	donor_gain	1.0000
4:9920384:C:CC	donor_gain	1.0000
4:9920384:CTG:C	donor_gain	1.0000
4:9920384:CTGC:C	donor_gain	1.0000
4:9942041:CTCTC:C	acceptor_gain	1.0000
4:9942043:CTC:C	acceptor_gain	1.0000
4:9980587:CTCA:C	donor_loss	1.0000
4:9980588:TCACC:T	donor_loss	1.0000
4:9980589:CA:C	donor_loss	1.0000
4:9980590:A:AC	donor_gain	1.0000
4:9980590:A:AG	donor_loss	1.0000
4:9980591:C:CC	donor_gain	1.0000
4:9980735:CGC:C	acceptor_gain	1.0000
4:9985663:TCTCA:T	donor_loss	1.0000
4:9985664:CTCAC:C	donor_loss	1.0000
4:9985665:TCACC:T	donor_loss	1.0000
4:9985666:CA:C	donor_loss	1.0000
4:9985667:A:AG	donor_loss	1.0000
4:10019069:CAGTC:C	acceptor_gain	0.9900
4:10019071:GTCCT:G	acceptor_loss	0.9900
4:10019074:C:CC	acceptor_gain	0.9900
4:10019075:T:G	acceptor_loss	0.9900
4:9834875:TCATA:T	donor_loss	0.9900
4:9834876:CATA:C	donor_loss	0.9900
4:9834877:ATAC:A	donor_loss	0.9900
4:9834878:TAC:T	donor_loss	0.9900
4:9834879:A:AG	donor_loss	0.9900

AlphaMissense

3488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:10019009:C:T	G72D	0.997
4:9887580:G:C	F426L	0.997
4:9887580:G:T	F426L	0.997
4:9887582:A:G	F426L	0.997
4:9985681:C:G	G175R	0.997
4:9980627:C:A	G216W	0.996
4:9980638:C:T	G212D	0.996
4:10019009:C:A	G72V	0.995
4:10019010:C:G	G72R	0.995
4:9941962:G:C	S255R	0.995
4:9941962:G:T	S255R	0.995
4:9941964:T:G	S255R	0.995
4:9980639:C:G	G212R	0.995
4:9996832:C:T	G120D	0.995
4:10019027:C:T	G66D	0.993
4:9920388:A:C	N333K	0.993
4:9920388:A:T	N333K	0.993
4:9942034:C:A	W231C	0.993
4:9942034:C:G	W231C	0.993
4:9942036:A:G	W231R	0.993
4:9942036:A:T	W231R	0.993
4:9985680:C:T	G175D	0.993
4:9985692:C:G	R171P	0.993
4:10019007:A:C	Y73D	0.992
4:10019010:C:A	G72C	0.992
4:9980626:C:T	G216E	0.992
4:9985680:C:A	G175V	0.992
4:10018987:A:C	N79K	0.991
4:10018987:A:T	N79K	0.991
4:10019000:A:G	L75P	0.991

dbSNP variants (sampled 300 via entrez): RS1000001088 (4:9873094 C>T), RS1000002421 (4:9951916 T>C), RS1000003363 (4:10007541 A>C), RS1000025796 (4:9933684 A>G,T), RS1000034911 (4:9903951 A>G), RS1000054154 (4:10030577 G>A), RS10000582 (4:9855071 A>C), RS1000058379 (4:9952181 G>C), RS1000076653 (4:10002641 T>A), RS1000080065 (4:9966211 A>G), RS1000082938 (4:9795330 C>T), RS10000983 (4:9949982 T>A,C), RS10001006 (4:9786874 C>A,T), RS1000100921 (4:9867329 C>G), RS1000107193 (4:9916418 C>T)

Disease associations

OMIM: gene MIM:606142 | disease phenotypes: MIM:612076, MIM:181500, MIM:613659

GenCC curated gene-disease

Disease	Classification	Inheritance
hypouricemia, renal, 2	Strong	Autosomal recessive
hereditary renal hypouricemia	Supportive	Autosomal recessive

Mondo (4): hypouricemia, renal, 2 (MONDO:0012793), schizophrenia (MONDO:0005090), gastric cancer (MONDO:0001056), hereditary renal hypouricemia (MONDO:0009071)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

19 total (20 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000091	Abnormal renal tubule morphology
HP:0000787	Nephrolithiasis
HP:0000790	Hematuria
HP:0001919	Acute kidney injury
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002150	Hypercalciuria
HP:0003138	Increased blood urea nitrogen
HP:0003149	Hyperuricosuria
HP:0003418	Back pain
HP:0003537	Hypouricemia
HP:0008651	Uric acid urolithiasis independent of gout
HP:0012211	Abnormal renal physiology
HP:0012213	Decreased glomerular filtration rate
HP:0012595	Mild proteinuria
HP:0012622	Chronic kidney disease
HP:0030973	Postexertional symptom exacerbation
HP:0100753	Schizophrenia

GWAS associations

86 associations (top):

Study	Trait	p-value
GCST000130_1	Urate levels	2.000000e-15
GCST000160_1	Urate levels	3.000000e-09
GCST000161_1	Urate levels	3.000000e-70
GCST000242_2	Urate levels	7.000000e-168
GCST000328_5	Biochemical measures	1.000000e-09
GCST000418_11	Uric acid levels	1.000000e-41
GCST000418_7	Uric acid levels	1.000000e-192
GCST000581_1	Urate levels	7.000000e-24
GCST000818_10	Urate levels	4.000000e-13
GCST000818_4	Urate levels	2.000000e-242
GCST000963_4	Uric acid levels	1.000000e-08
GCST001217_22	Metabolic traits	6.000000e-34
GCST001268_1	Gout	2.000000e-07
GCST001269_2	Serum uric acid levels	1.000000e-80
GCST001285_3	Psychosis and Alzheimer’s disease	5.000000e-06
GCST001374_1	Uric acid levels	2.000000e-19
GCST001608_2	Renal function-related traits (urate)	2.000000e-65
GCST001790_3	Gout	4.000000e-26
GCST001791_26	Urate levels	0.000000e+00
GCST001801_1	Uric acid levels	3.000000e-12
GCST001801_5	Uric acid levels	2.000000e-07
GCST001801_6	Uric acid levels	8.000000e-13
GCST002311_1	Serum uric acid levels	3.000000e-08
GCST002348_1	Cleft plate (environmental tobacco smoke interaction)	2.000000e-06
GCST002355_4	Serum uric acid levels	9.000000e-31
GCST002773_2	Gout	6.000000e-27
GCST002828_31	Urate levels in obese individuals	6.000000e-62
GCST002828_34	Urate levels in obese individuals	3.000000e-59
GCST002828_35	Urate levels in obese individuals	4.000000e-14
GCST002829_30	Urate levels in overweight individuals	3.000000e-92

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004761	uric acid measurement
EFO:0004725	metabolite measurement
EFO:0005940	psychotic symptoms
EFO:0008361	environmental tobacco smoke exposure measurement
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0009104	hyperuricemia
EFO:0010637	salivary metabolite measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567426	Hypouricemia, Renal, 2 (supp.)
C537757	Renal hypouricemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2052034 (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: 93,882 (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
CHEMBL140	CURCUMIN	3	93,882

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs16890979	SLC2A9		0.00	0
rs11942223	SLC2A9		0.00	0
rs62293298	SLC2A9		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Class II transporters

ChEMBL bioactivities

8 potent at pChembl≥5 of 14 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.50	IC50	320	nM	CHEMBL6149105
6.36	IC50	440	nM	CYTOCHALASIN B
5.95	IC50	1120	nM	ISOBAVACHIN
5.74	IC50	1840	nM	CHEMBL5618175
5.58	IC50	2630	nM	APIGENIN
5.35	IC50	4470	nM	CHEMBL5618375
5.03	IC50	9370	nM	CHEMBL5202967

PubChem BioAssay actives

3 with measured affinity, of 20 total; 3 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
7-hydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one	2129093: Inhibition of GLUT9 (unknown origin) overexpressed in uric acid-induced HEK293 cells by patch clamp analysis	ic50	1.8400	uM
(E)-4-[2-(4-bromonaphthalen-1-yl)-4-oxo-2,3-dihydrochromen-8-yl]-2-methylbut-2-enoic acid	2129093: Inhibition of GLUT9 (unknown origin) overexpressed in uric acid-induced HEK293 cells by patch clamp analysis	ic50	4.4700	uM
sodium 2-[[3-[(4-cyanonaphthalen-1-yl)amino]-4-pyridinyl]sulfanylmethyl]benzoate	1900886: Inhibition of GLUT9 (unknown origin) expressed in HEK293T cells assessed as inhibition of uric acid-induced current by whole cell patch clamp technique	ic50	9.3700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Uric Acid	affects transport, decreases secretion, decreases reaction, increases transport, increases reaction (+1 more)	4
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	affects methylation, decreases expression	2
Fructose	increases reaction, increases transport	2
Glucose	increases reaction, increases transport	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
Aflatoxin B1	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
arsenite	increases methylation	1
aflatoxin B2	increases methylation	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	affects methylation	1
Benzbromarone	decreases reaction, increases transport	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Chloride	decreases response to substance, increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 11 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2061376	Binding	Inhibition of GLUT9 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
CHEMBL5209625	Functional	Substrate uptake by the Glucose Transporter Type 9 (GLUT9, SLC2A9) as assessed by the fluorescent FLIPR membrane potential dye in HEK-293 cells stably transfected with SLC2A9 isoform 1 (PubChem AID: 1794831)	Membrane potential based assay for SLC2A9 using HEK-293 SLC2A9 OE cells

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D4E9	HEK-SLC2A9-KO-c6	Transformed cell line	Female
CVCL_D4VV	LS180-SLC2A9-KO-c2	Cancer cell line	Female
CVCL_D4VW	LS180-SLC2A9-KO-c3	Cancer cell line	Female
CVCL_E0NU	Ubigene HeLa SLC2A9 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04398251	PHASE4	UNKNOWN	A Randomized Clinical Trail of The Effect of Postoperative Uric Acid Control on Stone Recurrence and Renal Function in Patients With Hyperuricemia of Urolithiasis.
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients