SLC22A3

Summary

SLC22A3 (solute carrier family 22 member 3, HGNC:10967) is a protein-coding gene on chromosome 6q25.3, encoding Solute carrier family 22 member 3 (O75751). Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein.

Source: NCBI Gene 6581 — RefSeq curated summary.

At a glance

• GWAS associations: 57
• Clinical variants (ClinVar): 88 total
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10967
Approved symbol	SLC22A3
Name	solute carrier family 22 member 3
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	OCT3, EMT
Ensembl gene	ENSG00000146477
Ensembl biotype	protein_coding
OMIM	604842
Entrez	6581

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000275300, ENST00000855212, ENST00000855213, ENST00000855214

RefSeq mRNA: 1 — MANE Select: NM_021977 NM_021977

CCDS: CCDS5277

Canonical transcript exons

ENST00000275300 — 11 exons

Exon	Start	End
ENSE00000976037	160397979	160398082
ENSE00000976038	160407041	160407195
ENSE00000976039	160408753	160408921
ENSE00000976040	160410729	160410846
ENSE00000976041	160436780	160436877
ENSE00000976042	160436997	160437211
ENSE00000976043	160442761	160442869
ENSE00000976044	160443630	160443742
ENSE00000976045	160447719	160447818
ENSE00001443061	160450996	160452577
ENSE00001887130	160348378	160348848

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 96.03.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6091 / max 291.4276, expressed in 605 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71021	3.0292	522
71020	0.2571	150
71024	0.2246	118
71022	0.0467	19
71023	0.0282	10
71025	0.0233	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thoracic aorta	UBERON:0001515	96.03	gold quality
ascending aorta	UBERON:0001496	96.01	gold quality
descending thoracic aorta	UBERON:0002345	95.85	gold quality
tibial nerve	UBERON:0001323	94.65	gold quality
right coronary artery	UBERON:0001625	94.49	gold quality
blood vessel layer	UBERON:0004797	94.07	gold quality
aorta	UBERON:0000947	93.48	gold quality
gastrocnemius	UBERON:0001388	92.19	gold quality
left coronary artery	UBERON:0001626	92.15	gold quality
popliteal artery	UBERON:0002250	91.73	gold quality
tibial artery	UBERON:0007610	91.72	gold quality
artery	UBERON:0001637	91.51	gold quality
coronary artery	UBERON:0001621	90.48	gold quality
muscle of leg	UBERON:0001383	90.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.37	gold quality
right lobe of liver	UBERON:0001114	90.17	gold quality
left uterine tube	UBERON:0001303	89.25	gold quality
prostate gland	UBERON:0002367	86.68	gold quality
left ovary	UBERON:0002119	86.36	gold quality
right ovary	UBERON:0002118	86.31	gold quality
right adrenal gland cortex	UBERON:0035827	85.76	gold quality
sural nerve	UBERON:0015488	85.25	gold quality
seminal vesicle	UBERON:0000998	85.01	gold quality
adrenal tissue	UBERON:0018303	84.94	gold quality
skeletal muscle organ	UBERON:0014892	84.75	gold quality
muscle organ	UBERON:0001630	84.73	gold quality
left adrenal gland	UBERON:0001234	84.69	gold quality
right adrenal gland	UBERON:0001233	84.39	gold quality
left adrenal gland cortex	UBERON:0035825	84.38	gold quality
ectocervix	UBERON:0012249	84.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	21.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF8, POU5F1, PPARA

miRNA regulators (miRDB)

78 targeting SLC22A3, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-2681-5P	99.75	67.64	1655

Literature-anchored findings (GeneRIF, showing 40)

• The regulation of EMT-mediated transport by second-messenger phosphorylation/dephosphorylation mechanisms has been characterized in stably transfected HEK293 cells with tritiated 1-methyl-4-phenylpyridinium as substrate. (PMID:11770002)
• EMT efficiently translocates agmatine and must be considered for the control of agmatine levels. (PMID:12538837)
• Genetic variation of EMT was studied in Caucasians. (PMID:12768439)
• EMT is expressed in the area postrema of rat brain and may play a role in physiological functions of this circumventricular organ such as emesis, food intake and the regulation of cardiovascular functions. (PMID:14690517)
• organic cation transporter EMT mRNA was mainly detected in the intra lobular septa and also expressed in scattered cells of placental vessel adventitias with lower expression of EMT mRNAs in pre-eclamptic placentae (PMID:15135235)
• Ranitidine and famotidine elicited differential inhibitory activities on SLC22A3. (PMID:16141367)
• These results suggest that polymorphisms of SLC22A3 are related to the development of polysubstance use in Japanese patients with methamphetamine (MAP) dependence. (PMID:17010131)
• PMAT, EMT, and OCT2 transporters are expressed in the endometrial stroma and can potentially regulate reuptake of monoamines in general and histamine in particular. (PMID:17393420)
• rare mutations in the EMT gene suggest a causative or modulating role in genetic subtypes of obsessive-compulsive disorder (PMID:17477885)
• Confirm the usefulness of Caki-1 cells as a proximal tubule model system for investigations of OCT3. (PMID:18253050)
• We conclude that the proliferation of immature germ cells in GB may be due to an interaction between OCT3/4 and accumulated beta-catenin in the nuclei of the immature germ cells. (PMID:18295396)
• Identification of the SLC22A3-LPAL2-LPA gene cluster as a strong susceptibility locus for coronary artery disease. (PMID:19198611)
• Cholestasis and genetic variants are critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression in human liver. (PMID:19591196)
• The influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of the ensuing cytotoxicity such as DNA adduct formation, was determined. (PMID:20371711)
• There was no clear association between the SLC22A1, SLC22A2, and SLC22A3 genes and diabetic nephropathy or hypertension (PMID:20429798)
• Genetic association studies indicate 5 SNPs are associated with reduced transport activity of OCT3 (using 5-HT & MPP). (PMID:20562519)
• evidence for a new means of downregulating IL-4 production by basophils, both in vitro and in vivo, through OCT3 targeted by 5-HT and pharmacologic ligands. (PMID:21636115)
• SLC22A3 was expressed high in the human heart with strongest OCT3 immunoreactivity in vascular endothelial cells. SLC22A3/OCT3 expression was not changed in failing human left ventricular myocardium (PMID:21697722)
• OCT3 overexpression significantly increased cisplatin cellular accumulation and cytotoxicity in KB-3-1 cells. (PMID:21905038)
• Our studies demonstrate that genetic polymorphisms in the proximal promoter region of OCT3 alter the transcription rate of the gene and may be associated with altered expression levels of OCT3 in human liver. (PMID:22231567)
• NUDT11, HNF1B, and SLC22A3 genes have roles in prostate cancer pathogenesis (PMID:22730461)
• PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) SNPs might not be associated with prostate cancer in Chinese men. (PMID:22741436)
• The risk for coronary artery disease in a Chinese Han population is not associated with single nucleotide polymorphisms in the SLC22A3-LPAL2-LPA gene cluster. (PMID:23036009)
• The increased Wnt3 in the trastuzumab-resistant cells also promoted a partial EMT-like transition. (PMID:23071104)
• Decreasing expression of OCT3 and MATE1 in human placenta indicates these transporters may play a role in fetal protection preferentially at earlier stages of gestation. (PMID:23303678)
• There was no association between rs7758229 in 6q26-q27/SLC22A3 and the risk of colorectal cancer in a Chinese population. (PMID:23555006)
• Cultured astroctye line 1321N1 and primary human astrocytes transport monoamines partly through OCT3. (PMID:24471494)
• The markers of EMT were detected by using Western blot. (PMID:25322669)
• Findings suggest a negative feedback mechanism against inflammatory response by which solute carrier family 22 member 3 (SLC22A3) variant rs3088442 G–>A decreased the risk of coronary heart disease (CHD). (PMID:25561729)
• Findings suggest specific involvement of each organic cation transporters (OCT1-3) in drug transportation. (PMID:25883089)
• Findings suggest that OCT3 plays an important role in the absorption and elimination of metformin and that the transporter is a critical determinant of metformin bioavailability, clearance, and pharmacologic action. (PMID:25920679)
• The genotype of rs3088442 within the SLC22A3-LPAL2-LPA gene cluster may contribute to regulation of plasma Lp(a) levels and possibly to the severity of coronary artery disease in a Chinese Han population. (PMID:27417586)
• our study suggests that several PHACTR1 and SLC22A3 gene polymorphisms may exert a protective effect against the CAD in the Chinese Han male population. (PMID:27893421)
• may be a regulator of the concentration of norepinephrine in adipose tissue. (PMID:28034777)
• Data show that the common variation in the solute carrier family 22 member 3 (SLC22A3) gene is unlikely to significantly contribute to pancreatic cancer risk, and the rs2504938 single nucleotide polymorphism (SNP) in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. (PMID:28272475)
• A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal squamous cell carcinoma in high-risk individuals. (PMID:28533408)
• the rs3088442G>A variant as a genetic marker may potentially assist in the identification of individuals at an increased risk of T2D. (PMID:28625319)
• SLC22A3 deletion is associated with motor speech disorders, and language delays. (PMID:28767196)
• SNPs in SLC22A3 and H3F3B may influence lipid levels through altering the expression of local genes. (PMID:29894858)
• The rs3088442 G>A variant of SLC22A3 acts as a protective allele and is associated with the clinical response to metformin. Overexpression of microRNA 147 is associated with a downward expression of the SLC22A3 gene in patients who have type 2 diabetes. (PMID:30297296)

Cross-species orthologs

51 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a4	ENSDARG00000005335
danio_rerio	oatx	ENSDARG00000019713
danio_rerio	si:dkey-166k12.1	ENSDARG00000054690
danio_rerio	si:dkey-119m7.4	ENSDARG00000071049
danio_rerio	si:dkey-119m7.8	ENSDARG00000096654
mus_musculus	Slc22a3	ENSMUSG00000023828
rattus_norvegicus	Slc22a3	ENSRNOG00000022946
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), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), 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 3 — O75751 (reviewed: O75751)

Alternative names: Extraneuronal monoamine transporter, Organic cation transporter 3

All UniProt accessions (1): O75751

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics. Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient. Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter. Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain. Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency. May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow. May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier. Mediates the transport of polyamine spermidine and putrescine. Mediates the bidirectional transport of polyamine agmatine. Also transports guanidine. May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling.

Subcellular location. Cell membrane. Apical cell membrane. Basolateral cell membrane. Mitochondrion membrane. Endomembrane system. Nucleus membrane. Nucleus outer membrane.

Tissue specificity. Expressed in liver. Expressed in intestine. Expressed in kidney in proximal tubular cells. Expressed in placenta. Expressed throughout the brain, including cerebral cortex, cerebrellum, substancia nigra, medulla oblongata, hippocampus, caudate nucleus, nucleus accumbens and pons with low levels of expression detected in nearly all brain regions. In testis, mostly localized to peritubular myoid cells and Leydig cells, and weakly expressed in developing germ cells. Expressed in tracheal and bronchial epithelium of the respiratory tract, where it localizes to the apical membrane of ciliated cells, the entire membrane of basal cells and the basolateral membrane of intermediate cells. Expressed in skeletal muscle, adrenal gland, heart, prostate, aorta, salivary gland, adrenal gland, uterus, lymph node, lung, trachea and spinal cord. Expressed in fetal lung and liver.

Domain organisation. Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.

Miscellaneous. Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) and platinum-based drug oxaliplatin. Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity.

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

RefSeq proteins (1): NP_068812* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004749	Orgcat_transp/SVOP	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

Catalyzed reactions (Rhea), 11 shown:

• spermidine(in) = spermidine(out) (RHEA:35039)
• agmatine(out) = agmatine(in) (RHEA:72131)
• dopamine(out) = dopamine(in) (RHEA:73863)
• serotonin(out) = serotonin(in) (RHEA:73867)
• (R)-noradrenaline(out) = (R)-noradrenaline(in) (RHEA:73871)
• (R)-adrenaline(out) = (R)-adrenaline(in) (RHEA:73875)
• histamine(out) = histamine(in) (RHEA:73879)
• guanidine(out) = guanidine(in) (RHEA:73883)
• tyramine(in) = tyramine(out) (RHEA:74783)
• L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L-proline diketopiperazine(out) (RHEA:74787)
• (R)-salsolinol(in) = (R)-salsolinol(out) (RHEA:74791)

UniProt features (55 total): helix 28, transmembrane region 7, strand 7, glycosylation site 4, mutagenesis site 3, sequence variant 2, turn 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7ZH0	ELECTRON MICROSCOPY	3.2
7ZHA	ELECTRON MICROSCOPY	3.55
7ZH6	ELECTRON MICROSCOPY	3.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75751-F1	83.61	0.38

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 (4): 99, 119, 322, 72

Mutagenesis-validated functional residues (3):

Position	Phenotype
289	decreased tea uptake.
363	decreased tea uptake.
380	decreased tea uptake.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2161517	Abacavir transmembrane transport
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-2161522	Abacavir ADME
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-549132
R-HSA-9748784	Drug ADME

MSigDB gene sets: 169 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, MODULE_255, MODULE_317, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, chr6q25, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, GOBP_DETOXIFICATION, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_REGULATION_OF_APPETITE

GO Biological Process (28): histamine metabolic process (GO:0001692), monoatomic ion transport (GO:0006811), neurotransmitter transport (GO:0006836), obsolete serotonin transport (GO:0006837), obsolete organic cation transport (GO:0015695), quaternary ammonium group transport (GO:0015697), obsolete organic anion transport (GO:0015711), monocarboxylic acid transport (GO:0015718), obsolete monoamine transport (GO:0015844), spermidine transport (GO:0015848), obsolete dopamine transport (GO:0015872), obsolete norepinephrine transport (GO:0015874), regulation of appetite (GO:0032098), xenobiotic transport (GO:0042908), obsolete epinephrine transport (GO:0048241), histamine transport (GO:0051608), serotonin uptake (GO:0051610), histamine uptake (GO:0051615), norepinephrine uptake (GO:0051620), epinephrine uptake (GO:0051625), purine-containing compound transmembrane transport (GO:0072530), dopamine uptake (GO:0090494), transport across blood-brain barrier (GO:0150104), cellular detoxification (GO:1990748), organic hydroxy compound transport (GO:0015850), establishment of localization in cell (GO:0051649), transmembrane transport (GO:0055085), spermidine transmembrane transport (GO:1903711)

GO Molecular Function (9): neurotransmitter transmembrane transporter activity (GO:0005326), monoamine transmembrane transporter activity (GO:0008504), obsolete organic anion transmembrane transporter activity (GO:0008514), obsolete organic cation transmembrane transporter activity (GO:0015101), spermidine transmembrane transporter activity (GO:0015606), quaternary ammonium group transmembrane transporter activity (GO:0015651), toxin transmembrane transporter activity (GO:0019534), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (13): nuclear outer membrane (GO:0005640), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), mitochondrial membrane (GO:0031966), neuronal cell body (GO:0043025), presynapse (GO:0098793), nucleus (GO:0005634), mitochondrion (GO:0005739), basal plasma membrane (GO:0009925), nuclear membrane (GO:0031965)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Abacavir ADME	1
SLC-mediated transmembrane transport	1
Drug ADME	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	4
nitrogen compound transport	3
transmembrane transporter activity	3
cellular anatomical structure	3
plasma membrane region	3
organelle membrane	2
intracellular membrane-bounded organelle	2
biogenic amine metabolic process	1
imidazole-containing compound metabolic process	1
carboxylic acid transport	1
polyamine transport	1
response to nutrient levels	1
regulation of biological quality	1
organic hydroxy compound transport	1
neurotransmitter reuptake	1
neurotransmitter uptake	1
histamine transport	1
catecholamine uptake	1
neurotransmitter transport	1
active transmembrane transporter activity	1
polyamine transmembrane transporter activity	1
spermidine transmembrane transport	1
quaternary ammonium group transport	1
binding	1
transporter activity	1
transmembrane transport	1
nuclear membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
basal plasma membrane	1
apical part of cell	1
mitochondrion	1
mitochondrial envelope	1
somatodendritic compartment	1
cell body	1
synapse	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A3	IGF2R	P11717	904
SLC22A3	SLC6A2	P23975	822
SLC22A3	EHMT2	Q96KQ7	796
SLC22A3	SLC29A4	Q7RTT9	731
SLC22A3	SLC47A1	Q96FL8	716
SLC22A3	SLC6A4	P31645	715
SLC22A3	SLC47A2	Q86VL8	684
SLC22A3	YRDC	Q86U90	668
SLC22A3	Q92681	Q92681	659
SLC22A3	SLC6A3	Q01959	658
SLC22A3	SLC15A1	P46059	612
SLC22A3	SLC67A1	Q96BI1	579
SLC22A3	ZNF200	P98182	546
SLC22A3	SLCO2B1	O94956	539
SLC22A3	SLC18A2	Q05940	531

IntAct

124 interactions, top by confidence:

A	B	Type	Score
GRID2IP	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF12	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF2	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
SNTB1	SLC22A3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
SLC22A3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (20): SLC22A3 (Affinity Capture-RNA), SLC22A3 (Affinity Capture-RNA), SLC22A3 (Proximity Label-MS), SLC22A3 (Proximity Label-MS), SLC22A3 (Proximity Label-MS), SLC22A3 (Affinity Capture-MS), SLC22A3 (Proximity Label-MS), SLC22A3 (Proximity Label-MS), ACTG2 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), CAND1 (Affinity Capture-MS), FRMD5 (Affinity Capture-MS), HOOK2 (Affinity Capture-MS), IPO9 (Affinity Capture-MS), PBXIP1 (Affinity Capture-MS)

ESM2 similar proteins: A6NK97, A6QLW8, A7MBE0, A9CB25, B2GV36, O15245, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q3YAW7, Q4U2R8, Q4W8A2, Q4W8A3, Q5NCM1, Q5R540, Q5R9C4, Q5RCH6, Q5RLM2, Q66J52, Q66J54, Q6A4L0, Q6DFR1, Q6NUB3, Q6NWF1, Q6NYN7, Q70BM6, Q80UJ1, Q863T6, Q864Z3, Q86VW1, Q8HY24, Q8MK48, Q8R0S9, Q8TCC7, Q8VC69, Q91WU2, Q9H015

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 78 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	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	48.8×	6e-13
Dopamine Neurotransmitter Release Cycle	5	47.7×	2e-06
Long-term potentiation	5	45.8×	2e-06
Neurexins and neuroligins	11	41.6×	3e-13
Protein-protein interactions at synapses	7	35.8×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	84.1×	1e-16
protein localization to synapse	6	60.5×	7e-08
receptor clustering	7	57.5×	7e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	39.1×	9e-07
cell-cell adhesion	11	14.7×	4e-08
protein-containing complex assembly	9	13.5×	2e-06
establishment of localization in cell	5	10.6×	3e-03
chemical synaptic transmission	7	7.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2781 predictions. Top by Δscore:

Variant	Effect	Δscore
6:160397973:TCTCA:T	acceptor_loss	1.0000
6:160397974:CTCA:C	acceptor_loss	1.0000
6:160397975:TCA:T	acceptor_loss	1.0000
6:160397977:A:AG	acceptor_gain	1.0000
6:160397977:AGTTT:A	acceptor_gain	1.0000
6:160397978:G:GT	acceptor_gain	1.0000
6:160397978:GT:G	acceptor_gain	1.0000
6:160397978:GTT:G	acceptor_gain	1.0000
6:160397978:GTTT:G	acceptor_gain	1.0000
6:160397978:GTTTG:G	acceptor_gain	1.0000
6:160398078:GACAG:G	donor_gain	1.0000
6:160398083:G:C	donor_loss	1.0000
6:160398083:G:GG	donor_gain	1.0000
6:160398084:T:G	donor_loss	1.0000
6:160407036:A:G	acceptor_gain	1.0000
6:160407191:GATTG:G	donor_gain	1.0000
6:160407192:ATTGG:A	donor_loss	1.0000
6:160407193:TTGG:T	donor_loss	1.0000
6:160407194:TGGT:T	donor_loss	1.0000
6:160407195:GGTA:G	donor_loss	1.0000
6:160407196:G:A	donor_loss	1.0000
6:160407196:G:GG	donor_gain	1.0000
6:160407197:T:G	donor_loss	1.0000
6:160408751:A:AG	acceptor_gain	1.0000
6:160408752:G:GG	acceptor_gain	1.0000
6:160408752:GT:G	acceptor_gain	1.0000
6:160410727:AG:A	acceptor_gain	1.0000
6:160410727:AGGGT:A	acceptor_gain	1.0000
6:160410728:GG:G	acceptor_gain	1.0000
6:160410728:GGGTG:G	acceptor_gain	1.0000

AlphaMissense

3571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:160398039:G:C	G164R	0.997
6:160398040:G:A	G164D	0.997
6:160407153:G:C	G216R	0.997
6:160408821:G:A	G253R	0.997
6:160408821:G:C	G253R	0.997
6:160408865:G:C	W267C	0.997
6:160408865:G:T	W267C	0.997
6:160442869:G:C	R466P	0.997
6:160443638:G:A	G469E	0.997
6:160443651:T:G	C473W	0.997
6:160348614:G:C	W65C	0.996
6:160348614:G:T	W65C	0.996
6:160348812:G:C	W131C	0.996
6:160348812:G:T	W131C	0.996
6:160398052:G:A	G168E	0.996
6:160410751:T:A	W294R	0.996
6:160410751:T:C	W294R	0.996
6:160437022:G:A	G367R	0.996
6:160437022:G:C	G367R	0.996
6:160442843:T:A	N457K	0.996
6:160442843:T:G	N457K	0.996
6:160443649:T:C	C473R	0.996
6:160348540:T:C	F41L	0.995
6:160348542:C:A	F41L	0.995
6:160348542:C:G	F41L	0.995
6:160398051:G:A	G168R	0.995
6:160398051:G:C	G168R	0.995
6:160407049:G:T	R181M	0.995
6:160407142:G:C	R212P	0.995
6:160407154:G:A	G216D	0.995

dbSNP variants (sampled 300 via entrez): RS1000021601 (6:160394060 A>G), RS1000026041 (6:160432442 T>C,G), RS1000036580 (6:160400164 T>C), RS1000074634 (6:160439015 G>C), RS1000103551 (6:160350992 C>G), RS1000134703 (6:160351244 T>C), RS1000134991 (6:160392236 C>T), RS1000159847 (6:160420464 A>C), RS1000192524 (6:160367033 T>A), RS1000259543 (6:160418315 T>C), RS1000332797 (6:160372747 G>A), RS1000346690 (6:160431372 T>C), RS1000358027 (6:160445744 T>G), RS1000394329 (6:160452041 T>C,G), RS1000416699 (6:160369790 G>A,C,T)

Disease associations

OMIM: gene MIM:604842 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST000152_7	Prostate cancer	6.000000e-10
GCST000341_1	Coronary heart disease	4.000000e-15
GCST000341_2	Coronary heart disease	1.000000e-09
GCST000948_1	Colorectal cancer	8.000000e-09
GCST001218_4	Lp (a) levels	4.000000e-09
GCST001325_4	Response to hepatitis C treatment	2.000000e-06
GCST002287_13	Coronary artery disease or ischemic stroke	2.000000e-12
GCST002289_23	Coronary artery disease	1.000000e-06
GCST002290_2	Coronary artery disease or large artery stroke	9.000000e-14
GCST002601_2	Plasma plasminogen levels	2.000000e-15
GCST002890_10	Prostate cancer	4.000000e-12
GCST002944_57	Prostate cancer	6.000000e-12
GCST003116_13	Coronary artery disease	5.000000e-39
GCST003127_13	Lipoprotein (a) levels	2.000000e-34
GCST003586_2	Prostate cancer	3.000000e-09
GCST004787_35	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-49
GCST004894_137	Type 2 diabetes	2.000000e-10
GCST004904_35	Body mass index	2.000000e-12
GCST005950_13	Body mass index x sex x age interaction (4df test)	3.000000e-07
GCST005951_54	Body mass index	4.000000e-06
GCST005952_6	Body mass index (age>50)	2.000000e-08
GCST006626_26	Pulse pressure	1.000000e-11
GCST006867_55	Type 2 diabetes	3.000000e-10
GCST007638_35	Glycine levels	4.000000e-10
GCST007876_126	Estimated glomerular filtration rate	6.000000e-32
GCST008839_578	Height	2.000000e-10
GCST009379_60	Type 2 diabetes	8.000000e-10
GCST009881_1	Lipoprotein (a) levels in response to niacin in statin-treated individuals	7.000000e-28
GCST011330_3	Body mass index and coronary artery disease (pairwise)	3.000000e-10
GCST011331_4	Body mass index and systole blood pressure (pairwise)	7.000000e-10

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0006309	plasma plasminogen measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005763	pulse pressure measurement
EFO:0009767	glycine measurement
EFO:0006335	systolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007800	body fat percentage
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073673 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,341,955 (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
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL107	COLCHICINE	4	93,932
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL134	CLONIDINE	4	97,993
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL46	ONDANSETRON	4	41,386
CHEMBL481	IRINOTECAN	4	159,900
CHEMBL55	PENTAMIDINE	4	27,049
CHEMBL58	MITOXANTRONE	4	166,878
CHEMBL72	DESIPRAMINE	4	34,909
CHEMBL753	PHENOXYBENZAMINE	4	9,814
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL902	FAMOTIDINE	4	66,828
CHEMBL941	IMATINIB	4	111,611
CHEMBL110739	CORTICOSTERONE	3	28,274
CHEMBL2074647	METIPRENALINE	2	47

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2076828	Efficacy	3	metformin
rs8187725	Metabolism/PK	3	catecholamines;metformin

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs555754	SLC22A3		0.00	0
rs884742	SLC22A3		0.00	0
rs2076828	SLC22A3	3	1.75	1	metformin
rs8187725	SLC22A3	3	1.50	1	catecholamines;metformin
rs512077	SLC22A3		0.00	0
rs2504938	SLC22A3		0.00	0
rs2292334	SLC22A3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Organic cation transporters (OCT)

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

Ligand	Action	Affinity	Parameter
disprocynium24	Inhibition	7.82	pKi

ChEMBL bioactivities

23 potent at pChembl≥5 of 36 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	Ki	15	nM	DISPROCYNIUM24
7.30	IC50	50	nM	CHEMBL2074900
7.05	IC50	90	nM	CHEMBL1197556
6.92	Ki	120	nM	COLCHICINE
6.54	IC50	290	nM	CORTICOSTERONE
6.40	IC50	400	nM	CHEMBL4129927
6.39	IC50	410	nM	CHLORHEXIDINE
6.30	IC50	500	nM	NILOTINIB
5.82	IC50	1500	nM	CHEMBL4100146
5.80	IC50	1600	nM	CORTICOSTERONE
5.75	IC50	1760	nM	Cyanine-863
5.66	IC50	2200	nM	CHEMBL4062501
5.55	IC50	2800	nM	CHEMBL41040
5.54	IC50	2880	nM	ESTRADIOL
5.37	IC50	4280	nM	PROGESTERONE
5.36	IC50	4380	nM	METIPRENALINE
5.34	IC50	4600	nM	CHEMBL43415
5.32	IC50	4800	nM	CHEMBL1160763
5.26	IC50	5500	nM	BITHIONOL
5.21	IC50	6130	nM	PHENOXYBENZAMINE
5.12	IC50	7600	nM	CHEMBL13823
5.10	IC50	7900	nM	IBRUTINIB
5.02	IC50	9500	nM	PENTAMIDINE

PubChem BioAssay actives

23 with measured affinity, of 143 total; 22 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
(2Z)-1-propan-2-yl-2-[(1-propan-2-ylquinolin-1-ium-4-yl)methylidene]quinoline	680331: TP_TRANSPORTER: inhibition of MPP+ uptake in OCT3-expressing HEK293 cells	ki	0.0150	uM
N-(2-chloroethyl)-N-methyl-9H-fluoren-9-amine	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	0.0500	uM
(2E)-1-ethyl-2-[(1-ethylquinolin-1-ium-2-yl)methylidene]quinoline	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	0.0900	uM
Colchicine	680331: TP_TRANSPORTER: inhibition of MPP+ uptake in OCT3-expressing HEK293 cells	ki	0.1200	uM
(8S,9S,10R,11S,13S,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	0.2900	uM
(2E)-1-ethyl-2-[(1-ethylquinolin-1-ium-2-yl)methylidene]quinoline iodide	1912478: Inhibition of the Organic Cation Transporter 3 (OCT3, SLC22A3) as assessed by a phenotypic impedance-based assay detecting changes in cell morphology by MPP+ uptake in HEK-293 JumpIN-SLC22A3 cells (PubChem AID: 1745861)	ic50	0.4000	uM
Chlorhexidine	721749: Inhibition of human OCT3-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	0.4100	uM
Nilotinib	1912478: Inhibition of the Organic Cation Transporter 3 (OCT3, SLC22A3) as assessed by a phenotypic impedance-based assay detecting changes in cell morphology by MPP+ uptake in HEK-293 JumpIN-SLC22A3 cells (PubChem AID: 1745861)	ic50	0.5000	uM
2-(4-iodophenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	1.5000	uM
2-[(3,6-dimethyl-2-phenyl-4H-pyrimidin-4-yl)methyl]-1-ethylquinolin-1-ium chloride	679482: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.2 uM) in OCT3-expressing HEK293 cells	ic50	1.7600	uM
2-(4-tert-butylphenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	2.2000	uM
2-(4-chlorophenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	2.8000	uM
Estradiol	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	2.8800	uM
Progesterone	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	4.2800	uM
4-[1-hydroxy-2-(propan-2-ylamino)ethyl]-2-methoxyphenol	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	4.3800	uM
2-(4-methylphenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	4.6000	uM
2-(4-bromophenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	4.8000	uM
2,4-dichloro-6-(3,5-dichloro-2-hydroxyphenyl)sulfanylphenol	721749: Inhibition of human OCT3-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	5.5000	uM
Phenoxybenzamine	682144: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT3-expressing HEK293 cells	ic50	6.1300	uM
2-(3-chlorophenyl)guanidine	1463536: Inhibition of human OCT3 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	7.6000	uM
Ibrutinib	1912478: Inhibition of the Organic Cation Transporter 3 (OCT3, SLC22A3) as assessed by a phenotypic impedance-based assay detecting changes in cell morphology by MPP+ uptake in HEK-293 JumpIN-SLC22A3 cells (PubChem AID: 1745861)	ic50	7.9000	uM
Pentamidine	721749: Inhibition of human OCT3-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
1-Methyl-4-phenylpyridinium	increases transport, affects transport, affects uptake, decreases reaction, increases uptake	11
Benzo(a)pyrene	affects cotreatment, affects expression, decreases expression, increases methylation	9
Corticosterone	decreases reaction, increases import, increases uptake, decreases activity	5
Estradiol	affects cotreatment, increases expression, decreases reaction, increases uptake, decreases activity (+1 more)	4
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects expression	4
Aflatoxin B1	affects expression, decreases expression	4
Tetraethylammonium	increases uptake, decreases reaction	4
pseudoisocyanine	increases uptake, decreases reaction	3
Cimetidine	decreases reaction, increases uptake, increases transport	3
Cisplatin	affects expression, affects cotreatment, decreases expression, affects response to substance, increases uptake	3
Histamine	decreases reaction, increases uptake, affects uptake	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
bisphenol A	affects cotreatment, affects methylation, increases expression	2
sodium arsenite	decreases expression	2
Fluticasone	decreases transport, increases response to substance, decreases reaction, increases uptake	2
Formoterol Fumarate	increases uptake, decreases transport, increases response to substance, decreases reaction	2
Carvedilol	decreases reaction, increases uptake	2
Air Pollutants	decreases expression, increases abundance	2
Clonidine	increases transport, increases uptake, decreases reaction	2
Imipramine	decreases reaction, increases uptake	2
Metformin	increases uptake, decreases reaction	2
Quinine	decreases reaction, increases transport, increases uptake	2
Ranitidine	decreases reaction, increases transport, increases uptake, affects transport	2
Silicon Dioxide	decreases expression, increases expression	2
Verapamil	decreases reaction, increases uptake	2
Cadmium Chloride	increases abundance, increases expression	2
Budesonide	decreases reaction, increases uptake, decreases transport, increases response to substance	2
trimazosin	decreases reaction, increases uptake	1

ChEMBL screening assays

33 unique, capped per target: 17 binding, 11 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075862	Functional	TP_TRANSPORTER: uptake in OCT3-expressing HRPE cells	Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. — Am J Physiol Renal Physiol
CHEMBL2320301	Binding	Inhibition of human OCT3-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. — J Med Chem
CHEMBL4375700	ADMET	Substrate activity at OCT3 in human Caco2 cells assessed as protein-mediated drug uptake at 0.5 mM measured after 10 mins in absence of OCT1 substrate metformin by UPLC-MS/MS analysis	Bioactivatable Pseudotripeptidization of Cyclic Dipeptides To Increase the Affinity toward Oligopeptide Transporter 1 for Enhanced Oral Absorption: An Application to Cyclo(l-Hyp-l-Ser) (JBP485). — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2KB	HEK-OCT3	Transformed cell line	Female
CVCL_D4SA	HuH7-SLC22A3-KO-c14	Cancer cell line	Male
CVCL_D4SB	HuH7-SLC22A3-KO-c4	Cancer cell line	Male

Clinical trials (associated diseases)

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