SLC22A11

Summary

SLC22A11 (solute carrier family 22 member 11, HGNC:18120) is a protein-coding gene on chromosome 11q13.1, encoding Solute carrier family 22 member 11 (Q9NSA0). Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds.

The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and is found mainly in the kidney and in the placenta, where it may act to prevent potentially harmful organic anions from reaching the fetus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55867 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 85 total
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18120
Approved symbol	SLC22A11
Name	solute carrier family 22 member 11
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	OAT4
Ensembl gene	ENSG00000168065
Ensembl biotype	protein_coding
OMIM	607097
Entrez	55867

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000301891, ENST00000377581, ENST00000377585, ENST00000416590, ENST00000428570, ENST00000460745, ENST00000478051, ENST00000490834

RefSeq mRNA: 2 — MANE Select: NM_018484 NM_001307985, NM_018484

CCDS: CCDS76425, CCDS8074

Canonical transcript exons

ENST00000301891 — 10 exons

Exon	Start	End
ENSE00001120019	64565222	64565337
ENSE00001120028	64567599	64567813
ENSE00001120032	64568670	64568778
ENSE00001340536	64570979	64572875
ENSE00001897175	64555941	64556392
ENSE00003461291	64569652	64569858
ENSE00003500632	64562004	64562158
ENSE00003500824	64564308	64564428
ENSE00003603615	64559135	64559238
ENSE00003653442	64562267	64562435

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 90.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3861 / max 136.7435, expressed in 40 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114974	0.2575	29
114972	0.0894	6
114975	0.0264	10
114973	0.0093	4
114976	0.0034	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	90.36	gold quality
placenta	UBERON:0001987	89.94	gold quality
nephron tubule	UBERON:0001231	85.82	gold quality
kidney epithelium	UBERON:0004819	84.54	gold quality
kidney	UBERON:0002113	83.83	gold quality
metanephric glomerulus	UBERON:0004736	80.85	gold quality
renal glomerulus	UBERON:0000074	80.56	gold quality
cortex of kidney	UBERON:0001225	79.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.21	gold quality
metanephros	UBERON:0000081	73.75	gold quality
metanephros cortex	UBERON:0010533	72.39	gold quality
corpus epididymis	UBERON:0004359	72.21	gold quality
caput epididymis	UBERON:0004358	67.66	gold quality
adult organism	UBERON:0007023	66.24	gold quality
cervix squamous epithelium	UBERON:0006922	63.51	gold quality
diaphragm	UBERON:0001103	63.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	62.74	gold quality
olfactory bulb	UBERON:0002264	62.26	gold quality
left ventricle myocardium	UBERON:0006566	62.18	gold quality
type B pancreatic cell	CL:0000169	62.09	gold quality
cauda epididymis	UBERON:0004360	61.68	gold quality
renal medulla	UBERON:0000362	61.44	gold quality
tongue squamous epithelium	UBERON:0006919	59.24	gold quality
superficial temporal artery	UBERON:0001614	59.03	gold quality
cerebellar vermis	UBERON:0004720	58.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	57.68	gold quality
quadriceps femoris	UBERON:0001377	56.75	gold quality
vastus lateralis	UBERON:0001379	56.72	gold quality
myocardium	UBERON:0002349	56.61	gold quality
right adrenal gland cortex	UBERON:0035827	55.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1326.43
E-GEOD-83139	no	3.18
E-ANND-3	no	2.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting SLC22A11, 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-3646	100.00	73.56	5283
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4721	99.26	66.05	818

Literature-anchored findings (GeneRIF, showing 20)

• elucidation of the molecular mechanism for renal tetracycline transport by human organic anion transporters (hOATs) using proximal tubular cells stably expressing hOATs (PMID:11855680)
• Glycosylation serves as a means to specifically regulate hOAT4 function in vivo. (PMID:15576633)
• hOAT4 is the long-postulated, low-affinity apical urate anion exchanger that facilitates hydrochlorothiazide-associated hyperuricemia. (PMID:17229912)
• The interaction of PDZ proteins with hOAT4 may be cell-specific. In placenta, a different set of interacting proteins from PDZK1 and NHERF1 may be required to modulate hOAT4 activity. (PMID:17602283)
• The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis. (PMID:18414001)
• Findings suggest that hOAT4 and caveolin-1 share a cellular expression in the plasma membrane and caveolin-1 up-regulates the organic anionic compound uptake by hOAT4 under the normal physiological condition. (PMID:18985008)
• Several naturally occurring SNPs encode variant hOAT4s that may impair the renal tubular re-absorption of important drug substrates. (PMID:20015291)
• The down-regulation of hOAT4 activity by activation of protein kinase C and the up-regulation of hOAT4 activity by NHERF-1 are mediated through alteration of hOAT4 internalization. (PMID:20140636)
• Genetic variants of human organic anion transporter 4 demonstrate altered transport of endogenous substrates. (PMID:20668102)
• When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. (PMID:22753387)
• A common variant of OAT4/SLC22A11 is associated with renal underexcretion type gout in Japanese men. (PMID:24025986)
• Our analysis provides evidence for multiple ancestral-specific effects across the SLC22A11/SLC22A12 locus that presumably influence the activity of OAT4 and URAT1 and risk of gout. (PMID:24360580)
• SLC22A11 at the basal plasma membrane of human placental syncytiotrophoblasts plays a predominant role in the uptake of 16alpha-OH DHEAS for placental estriol synthesis. (PMID:25919187)
• modifies placental passage of perfluorinated alkyl acids, may decrease fetal exposure (PMID:26303760)
• The regulation of hOAT4 activity was mediated by sgk2 acting through Nedd4-2. (PMID:26740304)
• The first genome-wide association study for serum uric acid level in Indians revealed association of SLC2A9, SLC22A11 and ABCG2 gene variants at genome wide significance level in Type 2 diabetes patients. (PMID:26902266)
• our study discovered 3 novel population-specific functional genetic variants (rs6913677, rs2078267, rs8100011) in 2 novel (SLC22A11 and ZNF45) and 1 earlier reported gene (BAI3) for BMI in Indians. Our study decodes key genomic loci underlying obesity phenotype in Indians that may serve as prospective drug targets in future (PMID:32363570)
• Perfluoroalkyl substances (PFASs) are substrates of the renal human organic anion transporter 4 (OAT4). (PMID:36436016)
• The regulation of human organic anion transporter 4 by insulin-like growth factor 1 and protein kinase B signaling. (PMID:37487877)
• Examining the Association of Rare Allelic Variants in Urate Transporters SLC22A11, SLC22A13, and SLC17A1 with Hyperuricemia and Gout. (PMID:38222853)

Cross-species orthologs

52 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a4	ENSDARG00000005335
danio_rerio	oatx	ENSDARG00000019713
danio_rerio	si:dkey-166k12.1	ENSDARG00000054690
danio_rerio	slc22a15	ENSDARG00000055445
danio_rerio	si:dkey-119m7.4	ENSDARG00000071049
danio_rerio	slc22a21	ENSDARG00000094112
danio_rerio	si:dkey-119m7.8	ENSDARG00000096654
danio_rerio	slc22a5	ENSDARG00000101021
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG4630	FBGN0033809
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	SLC22A	FBGN0037140
drosophila_melanogaster	CG7458	FBGN0037144
drosophila_melanogaster	CG14691	FBGN0037829
drosophila_melanogaster	CG14855	FBGN0038260
drosophila_melanogaster	CG14856	FBGN0038261
drosophila_melanogaster	CG14857	FBGN0038262
drosophila_melanogaster	CG12783	FBGN0038448
drosophila_melanogaster	CG7333	FBGN0038715
drosophila_melanogaster	CG7342	FBGN0038716
drosophila_melanogaster	CG17751	FBGN0038717
drosophila_melanogaster	CG17752	FBGN0038718
drosophila_melanogaster	CG16727	FBGN0038719
drosophila_melanogaster	CG6231	FBGN0038720
drosophila_melanogaster	CG4465	FBGN0038750
drosophila_melanogaster	CG4462	FBGN0038752
drosophila_melanogaster	CG4459	FBGN0038753
drosophila_melanogaster	CG6356	FBGN0039178
drosophila_melanogaster	CG3690	FBGN0040350
drosophila_melanogaster	CG31103	FBGN0051103
drosophila_melanogaster	CG31106	FBGN0051106
drosophila_melanogaster	CG31272	FBGN0051272
drosophila_melanogaster	CG33233	FBGN0053233
drosophila_melanogaster	CG33234	FBGN0053234
drosophila_melanogaster	Orct2	FBGN0086365
drosophila_melanogaster	CG42269	FBGN0259164
drosophila_melanogaster	CG44098	FBGN0264907
caenorhabditis_elegans		WBGENE00003837
caenorhabditis_elegans	oct-1	WBGENE00003842
caenorhabditis_elegans		WBGENE00003843
caenorhabditis_elegans		WBGENE00006220
caenorhabditis_elegans		WBGENE00008110
caenorhabditis_elegans		WBGENE00011456
caenorhabditis_elegans		WBGENE00014127
caenorhabditis_elegans		WBGENE00015088
caenorhabditis_elegans		WBGENE00017751
caenorhabditis_elegans		WBGENE00019408
caenorhabditis_elegans		WBGENE00020701
caenorhabditis_elegans		WBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A2 (ENSG00000112499), SLC22A7 (ENSG00000137204), SLC22A23 (ENSG00000137266), SLC22A14 (ENSG00000144671), SLC22A3 (ENSG00000146477), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Solute carrier family 22 member 11 — Q9NSA0 (reviewed: Q9NSA0)

Alternative names: Organic anion transporter 4, Organic anion:dicarboxylate exchanger OAT4

All UniProt accessions (4): A6NCG2, Q9NSA0, H7C0B7, H7C3R9

UniProt curated annotations — full annotation on UniProt →

Function. Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds. May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus. Maybe also be involved in placental urate homeostasis. Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates. Organic anion glutarate acts as conteranion for E1S renal uptake. Possible transport mode may also include DHEA-S/E1S exchange. Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion. Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A. Mediates the unidirectional efflux of glutamate and aspartate. Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S.

Subcellular location. Cell membrane. Apical cell membrane. Basal cell membrane.

Tissue specificity. Expressed in placental trophoblasts, syncytiotrophoblast and cytotrophoblast. Also located in the proximal tubules in kidneys.

Post-translational modifications. N-glycosylated. Contains several complex-type N-glycans.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NSA0-1	1	yes
Q9NSA0-2	2

RefSeq proteins (2): NP_001294914, NP_060954* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005828	MFS_sugar_transport-like	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 4 shown:

• prostaglandin E2(out) = prostaglandin E2(in) (RHEA:50984)
• prostaglandin F2alpha(out) = prostaglandin F2alpha(in) (RHEA:50988)
• dehydroepiandrosterone 3-sulfate(out) = dehydroepiandrosterone 3-sulfate(in) (RHEA:71839)
• estrone 3-sulfate(out) + glutarate(in) = estrone 3-sulfate(in) + glutarate(out) (RHEA:72151)

UniProt features (78 total): helix 27, topological domain 13, transmembrane region 12, mutagenesis site 11, strand 5, glycosylation site 3, sequence conflict 2, chain 1, region of interest 1, splice variant 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9U5A	ELECTRON MICROSCOPY	2.98
9M9Y	ELECTRON MICROSCOPY	3.04
8WJH	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSA0-F1	87.74	0.56

Functional residue map

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

Glycosylation sites (3): 39, 56, 99

Mutagenesis-validated functional residues (11):

Position	Phenotype
39	no visible effect on n-glycosylation. loss of n-glycosylation and of cell surface location; when associated with q-56; q
47	reduced cell surface expression and estrone 3-sulfate transport. reduced cell surface expression and estrone 3-sulfate t
52	slightly reduced estrone 3-sulfate transport. reduced cell surface expression and estrone 3-sulfate transport; when asso
56	no visible effect on n-glycosylation. loss of n-glycosylation and of cell surface expression; when associated with q-39;
63	no visible effect on n-glycosylation. loss of n-glycosylation and of cell surface expression; when associated with q-39;
83	reduced cell surface expression and estrone 3-sulfate transport; when associated with a-47; a-52; a-305 and a-469.
99	no visible effect on n-glycosylation. loss of n-glycosylation and of cell surface expression; when associated with q-39;
241	strongly reduced cell surface expression and estrone 3-sulfate transport.
305	reduced cell surface expression and estrone 3-sulfate transport; when associated with a-47; a-52; a-83 and a-469.
400	strongly reduced cell surface expression and estrone 3-sulfate transport.
469	slightly reduced estrone 3-sulfate transport. reduced cell surface expression and estrone 3-sulfate transport; when asso

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-561048	Organic anion transport by SLC22 transporters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-549132

MSigDB gene sets: 82 (showing top): GOCC_CELL_SURFACE, TGACCTY_ERR1_Q2, chr11q13, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, AACTTT_UNKNOWN, GOBP_URATE_METABOLIC_PROCESS, IK3_01, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_LIPID_LOCALIZATION, GOBP_FATTY_ACID_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP

GO Biological Process (6): monoatomic ion transport (GO:0006811), obsolete organic anion transport (GO:0015711), prostaglandin transport (GO:0015732), urate metabolic process (GO:0046415), inorganic anion transport (GO:0015698), transmembrane transport (GO:0055085)

GO Molecular Function (7): solute:inorganic anion antiporter activity (GO:0005452), obsolete organic anion transmembrane transporter activity (GO:0008514), prostaglandin transmembrane transporter activity (GO:0015132), obsolete sodium-independent organic anion transmembrane transporter activity (GO:0015347), protein binding (GO:0005515), antiporter activity (GO:0015297), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), basal plasma membrane (GO:0009925), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transport of organic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
plasma membrane region	2
fatty acid transport	1
icosanoid transport	1
small molecule metabolic process	1
purine-containing compound metabolic process	1
cellular process	1
antiporter activity	1
prostaglandin transport	1
icosanoid transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
basal part of cell	1
apical part of cell	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A11	SLC2A9	Q9NRM0	976
SLC22A11	SLC17A1	Q14916	924
SLC22A11	ABCC4	O15439	821
SLC22A11	PDZK1	Q5T2W1	816
SLC22A11	SLC17A3	O00476	800
SLC22A11	SLC47A2	Q86VL8	760
SLC22A11	SLC16A9	Q7RTY1	757
SLC22A11	SLC47A1	Q96FL8	750
SLC22A11	SLC5A12	Q1EHB4	740
SLC22A11	ABCG2	Q9UNQ0	730
SLC22A11	SLC5A8	Q8N695	709
SLC22A11	SLCO2B1	O94956	669
SLC22A11	SLCO4C1	Q6ZQN7	666
SLC22A11	CARMIL1	Q5VZK9	658
SLC22A11	SLCO1A2	P46721	652

IntAct

123 interactions, top by confidence:

A	B	Type	Score
SLC22A11	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	SLC22A11	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
PDZD2	SLC22A11	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
GOPC	SLC22A11	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A11	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (146): SLC22A11 (Affinity Capture-MS), NEDD4L (Affinity Capture-Western), NEDD4L (Affinity Capture-Western), SLC22A11 (Affinity Capture-Western), SLC22A11 (Affinity Capture-MS), AARS2 (Affinity Capture-MS), ACTR2 (Affinity Capture-MS), ADAM17 (Affinity Capture-MS), ADSS (Affinity Capture-MS), AHSA1 (Affinity Capture-MS), ALDH1A3 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS), KIAA1244 (Affinity Capture-MS), ARHGEF40 (Affinity Capture-MS)

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: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, B2GV36, G1SZD9, O34691, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R540, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63ZE4, Q66J52, Q66J54, Q6A4L0, Q6NYN7, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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	53.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	6e-13
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	11	40.9×	3e-13
Protein-protein interactions at synapses	7	35.1×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	80.9×	2e-16
protein localization to synapse	6	58.2×	8e-08
receptor clustering	7	55.3×	8e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	43.9×	3e-08
protein-containing complex assembly	9	13.0×	2e-06
cell-cell adhesion	10	12.8×	4e-07
regulation of small GTPase mediated signal transduction	5	9.1×	4e-03
chemical synaptic transmission	7	6.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1978 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64556390:AAG:A	donor_loss	1.0000
11:64556391:AG:A	donor_loss	1.0000
11:64556392:GG:G	donor_loss	1.0000
11:64556394:T:C	donor_loss	1.0000
11:64561999:GACAG:G	acceptor_loss	1.0000
11:64562001:CAGG:C	acceptor_loss	1.0000
11:64562155:CTGA:C	donor_loss	1.0000
11:64562156:TGA:T	donor_gain	1.0000
11:64562156:TGAGT:T	donor_loss	1.0000
11:64562157:GAG:G	donor_gain	1.0000
11:64562158:AGT:A	donor_loss	1.0000
11:64562159:G:GG	donor_gain	1.0000
11:64562159:GTGA:G	donor_loss	1.0000
11:64562265:A:AG	acceptor_gain	1.0000
11:64562265:AGT:A	acceptor_gain	1.0000
11:64562266:G:GT	acceptor_gain	1.0000
11:64562266:GT:G	acceptor_gain	1.0000
11:64562266:GTG:G	acceptor_gain	1.0000
11:64562266:GTGGT:G	acceptor_gain	1.0000
11:64562440:G:GG	donor_gain	1.0000
11:64565335:G:GT	donor_gain	1.0000
11:64565338:G:GG	donor_gain	1.0000
11:64569859:G:GG	donor_gain	1.0000
11:64559133:A:AG	acceptor_gain	0.9900
11:64559134:G:GG	acceptor_gain	0.9900
11:64561996:T:A	acceptor_gain	0.9900
11:64561998:T:TA	acceptor_gain	0.9900
11:64562003:GGTTT:G	acceptor_gain	0.9900
11:64562151:GACAC:G	donor_gain	0.9900
11:64562154:ACTGA:A	donor_gain	0.9900

AlphaMissense

3554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64562329:A:C	S239R	0.983
11:64562331:C:A	S239R	0.983
11:64562331:C:G	S239R	0.983
11:64569782:A:C	S505R	0.978
11:64569784:C:A	S505R	0.978
11:64569784:C:G	S505R	0.978
11:64568726:A:C	S444R	0.976
11:64568728:C:A	S444R	0.976
11:64568728:C:G	S444R	0.976
11:64556261:T:C	F88L	0.975
11:64556263:C:A	F88L	0.975
11:64556263:C:G	F88L	0.975
11:64556117:T:C	F40L	0.972
11:64556119:C:A	F40L	0.972
11:64556119:C:G	F40L	0.972
11:64556144:T:A	C49S	0.967
11:64556145:G:C	C49S	0.967
11:64556006:T:C	F3L	0.964
11:64556008:C:A	F3L	0.964
11:64556008:C:G	F3L	0.964
11:64567778:G:A	G413D	0.964
11:64567685:G:A	G382E	0.963
11:64556350:G:C	W117C	0.962
11:64556350:G:T	W117C	0.962
11:64568714:T:C	C440R	0.962
11:64556045:T:C	F16L	0.961
11:64556047:C:A	F16L	0.961
11:64556047:C:G	F16L	0.961
11:64567777:G:C	G413R	0.961
11:64567684:G:A	G382R	0.957

dbSNP variants (sampled 300 via entrez): RS1000150332 (11:64562957 G>A), RS1000261909 (11:64559781 G>A,T), RS1000431353 (11:64565072 C>T), RS1000651835 (11:64560002 C>G,T), RS1001223455 (11:64571487 C>A,T), RS1001367835 (11:64559431 C>A,T), RS1001402580 (11:64554970 C>T), RS1001503474 (11:64559656 T>C), RS1001665587 (11:64565527 G>A), RS1002228782 (11:64559808 G>A), RS1002661030 (11:64555288 C>T), RS1002875059 (11:64566483 T>G), RS1002940502 (11:64566224 C>G,T), RS1003038205 (11:64560663 C>G,T), RS1003176171 (11:64561179 G>A)

Disease associations

OMIM: gene MIM:607097 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000418_3	Uric acid levels	7.000000e-14
GCST000818_11	Urate levels	1.000000e-06
GCST000818_8	Urate levels	2.000000e-26
GCST001762_870	Obesity-related traits	3.000000e-06
GCST001791_30	Urate levels	9.000000e-38
GCST002829_22	Urate levels in overweight individuals	7.000000e-07
GCST002829_33	Urate levels in overweight individuals	1.000000e-10
GCST002830_12	Urate levels in lean individuals	7.000000e-08
GCST002830_33	Urate levels in lean individuals	6.000000e-08
GCST003359_2	Serum uric acid levels	3.000000e-11
GCST007400_66	Systemic lupus erythematosus	4.000000e-06
GCST007733_64	Serum uric acid levels	1.000000e-300
GCST007733_7	Serum uric acid levels	7.000000e-31
GCST008971_55	Urate levels	4.000000e-92
GCST008972_124	Urate levels	0.000000e+00
GCST008972_165	Urate levels	2.000000e-15
GCST010276_14	Renal underexcretion gout	1.000000e-10
GCST010277_11	Gout	2.000000e-21
GCST010721_2	Body mass index	5.000000e-08
GCST012338_27	Gout	2.000000e-37
GCST012339_8	Gout vs asymptomatic hyperuricemia	7.000000e-16
GCST90020025_1876	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_1493	Waist-hip index	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004531	urate measurement
EFO:0005116	urinary metabolite measurement
EFO:0004340	body mass index
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073677 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 332,133 (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
CHEMBL1146	CEFAMANDOLE	4	21,886
CHEMBL1435	CEFAZOLIN	4	37,670
CHEMBL161	CEFTRIAXONE	4	71,135
CHEMBL1730	CEFOTAXIME	4	480
CHEMBL2105720	LESINURAD	4	604
CHEMBL316157	CEPHALORIDINE	4	45,474
CHEMBL507674	CEFOPERAZONE	4	23,712
CHEMBL617	CEPHALOTHIN	4	24,927
CHEMBL897	PROBENECID	4	105,640
CHEMBL52333	ROLOFYLLINE	3	421
CHEMBL3707347	VERINURAD	2	184

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11231809	Efficacy	3	methotrexate	Rheumatoid arthritis

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11231809	SLC22A11	3	2.50	1	methotrexate
rs2078267	SLC22A11		0.00	0
rs17300741	SLC22A11		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Organic anion transporters (OATs)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
cefalotin	Inhibition	6.7	pKi

ChEMBL bioactivities

13 potent at pChembl≥5 of 20 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	Ki	200	nM	CEPHALOTHIN
5.94	Ki	1140	nM	CEFAMANDOLE
5.76	Ki	1740	nM	CEFAZOLIN
5.69	IC50	2030	nM	LESINURAD
5.62	Ki	2380	nM	CEFTRIAXONE
5.55	Ki	2800	nM	CEFOPERAZONE
5.44	Ki	3630	nM	CEPHALORIDINE
5.43	IC50	3700	nM	LESINURAD
5.23	IC50	5900	nM	VERINURAD
5.21	Ki	6150	nM	CEFOTAXIME
5.14	IC50	7300	nM	LESINURAD
5.07	IC50	8500	nM	CHEMBL3929544
5.03	IC50	9400	nM	CHEMBL3924161

PubChem BioAssay actives

10 with measured affinity, of 79 total; 8 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
(6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	0.2000	uM
(6R,7R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	1.1400	uM
Cefazolin	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	1.7400	uM
2-[[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-1,2,4-triazol-3-yl]sulfanyl]acetic acid	1559411: Inhibition of human OAT4 expressed in HEK293 cells by assessed as [14C]urate uptake preincubated for 5 mins followed by [14C]urate addition and measured after 10 mins by liquid scintillation counting method	ic50	2.0300	uM
Ceftriaxone	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	2.3800	uM
(6R,7R)-7-[[(2R)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	2.8000	uM
(6R,7R)-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	3.6300	uM
Cefotaxime	681569: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT4-expressing S2 cells	ki	6.1500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
estrone sulfate	increases uptake, increases transport, increases export, increases reaction, increases import (+2 more)	6
Probenecid	increases import, increases uptake, increases chemical synthesis, decreases activity, affects transport (+1 more)	6
perfluorooctanoic acid	increases import, increases reaction, decreases reaction, increases uptake, decreases activity (+1 more)	3
Diclofenac	affects transport, decreases reaction, increases uptake, decreases activity	3
Sulfobromophthalein	decreases reaction, increases import, increases uptake, decreases activity, affects transport	3
Aflatoxin B1	decreases methylation, increases expression, increases methylation, decreases reaction	3
bisphenol A	decreases expression, increases methylation	2
tetrabromobisphenol A	increases uptake, decreases activity, increases expression, decreases reaction	2
6-carboxyfluorescein	increases uptake, increases import, increases reaction, decreases reaction	2
perfluorodecanoic acid	decreases reaction, increases import, increases transport	2
perfluorooctane sulfonic acid	increases transport, decreases reaction, increases uptake, decreases activity	2
perfluoro-n-heptanoic acid	decreases reaction, increases import, increases transport	2
perfluoro-n-nonanoic acid	decreases reaction, increases import, increases transport	2
Benzo(a)pyrene	increases expression, increases methylation	2
Ibuprofen	affects transport, decreases reaction, decreases activity	2
Indomethacin	decreases reaction, decreases activity, affects transport	2
p-Aminohippuric Acid	increases import, increases export, increases reaction	2
aristolochic acid I	increases export, increases reaction, decreases reaction, increases uptake	1
lesinurad	decreases reaction, increases uptake, decreases activity	1
bisphenol F	increases uptake, decreases reaction	1
mivebresib	decreases expression	1
2,4,6-tribromophenol	increases expression	1
daidzein	decreases reaction, increases transport	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
butyraldehyde	decreases expression	1
4-methylumbelliferyl sulfate	affects transport, decreases reaction	1
4-nitrophenyl sulfate	affects transport, decreases reaction	1
ochratoxin A	affects transport	1
benzo(e)pyrene	decreases methylation	1

ChEMBL screening assays

63 unique, capped per target: 53 functional, 6 binding, 3 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1217027	Binding	Inhibition of human OAT4	alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists: from bench to bedside. — J Med Chem
CHEMBL2075309	Functional	TP_TRANSPORTER: uptake in OAT4-expressing S2 cells	Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. — J Pharmacol Exp Ther
CHEMBL3531370	ADMET	Inhibition of OAT4 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]E-sul substrate uptake at 500 uM by liquid scintillation counting	Evaluation and prediction of potential drug-drug interactions of linagliptin using in vitro cell culture methods. — Drug Metab Dispos

Clinical trials (associated diseases)

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