SLC22A1

Summary

SLC22A1 (solute carrier family 22 member 1, HGNC:10963) is a protein-coding gene on chromosome 6q25.3, encoding Solute carrier family 22 member 1 (O15245). 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter.

Source: NCBI Gene 6580 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 98 total
• Druggable target: yes — 86 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10963
Approved symbol	SLC22A1
Name	solute carrier family 22 member 1
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	OCT1
Ensembl gene	ENSG00000175003
Ensembl biotype	protein_coding
OMIM	602607
Entrez	6580

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000324965, ENST00000366963, ENST00000457470, ENST00000460902, ENST00000478607, ENST00000539263, ENST00000540443, ENST00000898295, ENST00000898296, ENST00000898297, ENST00000898298, ENST00000898299, ENST00000898300, ENST00000898301, ENST00000898302, ENST00000898303, ENST00000898304, ENST00000898305

RefSeq mRNA: 2 — MANE Select: NM_003057 NM_003057, NM_153187

CCDS: CCDS5274, CCDS5275

Canonical transcript exons

ENST00000366963 — 11 exons

Exon	Start	End
ENSE00001203446	160130104	160130207
ENSE00001950738	160121815	160122346
ENSE00003461379	160133957	160134125
ENSE00003474224	160136220	160136334
ENSE00003485457	160136544	160136650
ENSE00003509506	160154798	160154910
ENSE00003559342	160139653	160139867
ENSE00003596736	160158516	160158718
ENSE00003617739	160155975	160156074
ENSE00003648554	160132232	160132386
ENSE00003694220	160143541	160143649

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 99.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5403 / max 939.4280, expressed in 11 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71014	1.3608	11
71013	0.1678	7
71015	0.0116	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.58	gold quality
liver	UBERON:0002107	97.63	gold quality
cartilage tissue	UBERON:0002418	84.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.22	gold quality
blood	UBERON:0000178	75.95	gold quality
diaphragm	UBERON:0001103	73.18	gold quality
periodontal ligament	UBERON:0008266	71.84	silver quality
granulocyte	CL:0000094	70.58	gold quality
spleen	UBERON:0002106	69.63	gold quality
lower esophagus mucosa	UBERON:0035834	69.48	gold quality
stromal cell of endometrium	CL:0002255	68.57	gold quality
left lobe of thyroid gland	UBERON:0001120	68.03	gold quality
sural nerve	UBERON:0015488	67.99	gold quality
gastrocnemius	UBERON:0001388	67.86	gold quality
right lobe of thyroid gland	UBERON:0001119	67.29	gold quality
bone marrow cell	CL:0002092	66.86	silver quality
muscle of leg	UBERON:0001383	66.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.48	gold quality
thyroid gland	UBERON:0002046	66.07	gold quality
muscle organ	UBERON:0001630	65.73	gold quality
metanephros cortex	UBERON:0010533	65.62	gold quality
frontal pole	UBERON:0002795	65.59	gold quality
paraflocculus	UBERON:0005351	65.36	gold quality
middle frontal gyrus	UBERON:0002702	65.29	gold quality
endometrium epithelium	UBERON:0004811	65.25	gold quality
left adrenal gland cortex	UBERON:0035825	64.84	gold quality
adult mammalian kidney	UBERON:0000082	64.03	gold quality
ectocervix	UBERON:0012249	64.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.99	gold quality
gall bladder	UBERON:0002110	63.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	55.91
E-ANND-3	no	3.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, HNF4A, PPARA

miRNA regulators (miRDB)

13 targeting SLC22A1, 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-544A	99.84	68.66	1965
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-4740-5P	96.25	67.96	726
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694
HSA-MIR-3186-5P	87.11	67.29	51

Literature-anchored findings (GeneRIF, showing 40)

• investigation of polymorphisms affecting function (PMID:12439217)
• identification of genetic variations and their functional consequences (PMID:12439218)
• Evolutionary conserved amino acids predict the function of variants of this protein. (PMID:12719534)
• identification of single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions (PMID:14697261)
• organic cation transporter EMT mRNA was mainly detected in the intra lobular septa and together with organic cation transporters OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias (PMID:15135235)
• hOCT1 was inhibited by PKA and endogenously activated by calmodulin, calmodulin-dependent kinase II, and p56(lck) tyrosine kinase (PMID:15389554)
• Twenty genetic variations, including seven novel ones, have been found in the human SLC22A1 gene from 116 Japanese individuals. (PMID:15499200)
• OCT1 and OCT2 mediate luminal ACh release in human airways (PMID:15817714)
• Ranitidine and famotidine elicited differential inhibitory activities on SLC22A1. (PMID:16141367)
• interpatient variability in IC50(imatinib) is mainly due to differences in the efficiency of imatinib intracellular uptake and retention, mediated by OCT1 (PMID:16597591)
• findings suggest that genetic variants of hOCTs are not linked among three genes in a Korean population, and several of the hOCT genetic variants cause decreased transport activity in vitro compared with the wild type (PMID:17220237)
• The organic cation transporter 2 (OCT2) mRNA expression was exclusively detected in few scattered stromal cells and OCT1 mRNA was not detected at all. (PMID:17393420)
• Genetic variation in OCT1 may be associated with variation in response to metformin. (PMID:17476361)
• Expression of hOCT1 is important in determining the clinical response to imatinib. (PMID:17568400)
• OCT1 genotype is a determinant of metformin pharmacokinetics. (PMID:17609683)
• Cholesterol treatment led to increased levels of NTCP and OCT-1 mRNAs. (PMID:17635184)
• These results suggest that the saturable component in the hepatic uptake of these cationic compounds may be mediated mainly by hOCT1/rOct1. (PMID:17701831)
• P-gp, rather than BCRP or OCT1, is partially responsible for the development of imatinib-resistance due to constitutive and functional overexpression, leading to reduced intracellular accumulation of imatinib in resistant K562 cells. (PMID:17934801)
• Varenicline was characterized as a moderate-affinity substrate for hOCT2 (K(m)=370 microM) and its hOCT2-mediated uptake was partially inhibited by cimetidine. (PMID:17971819)
• SLC22A1 expression is a composite surrogate for expression of various transporters relevant to imatinib intracellular uptake and retention (PMID:18483382)
• Unlike imatinib, dasatinib cellular uptake is not significantly affected by OCT-1 activity, so that expression and function of OCT-1 is unlikely to affect response to dasatinib. (PMID:18559609)
• hOCT1 is not required for dasatinib uptake in human cells (PMID:18669873)
• Heterozygote R61C genotype (C/T) was demonstrated in five of 32 CML patients treated with imatinib; there is no evidence that response to imatinib treatment is impaired in R61C heterozygote individuals (PMID:19021069)
• The SLC22A1 loss-of-function variant does not attenuate the hemoglobin A1c reduction achieved by metformin in type 2 diabetics. (PMID:19336679)
• Data show that the GG genotype in ABCG2, AA genotype in CYP3A5 were associated with poor response to IM, whereas the GG genotype at SLC22A1 was correlated with high rate of loss of response or treatment failure to IM therapy. (PMID:19584153)
• Cholestasis and genetic variants are critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression in human liver. (PMID:19591196)
• YM155 is a substrate for OCT1 and OCT2, whereas it is unlikely for OCT3. (PMID:19833842)
• interaction between polymorphisms and MATE1 transporter polymorphisms on the glucose lowering effect of metformin (PMID:19898263)
• hOCT1 has no association with the stage and course of chronic myelogeneous leukemia, nor with the effectiveness of imatinib mesylate therapy. (PMID:19950608)
• There is no correlation between the polymorphisms of hOCT1-P283L, R287G, M408V and secondary imatinib resistance in CML patients, but the polymorphisms of hOCT1-283T, 287G may be good predictors for IM response. (PMID:19954617)
• Results reveal the presence of different protein complexes, including GATA-1 and Oct-1, involved in Gfi1b regulation. (PMID:20143233)
• Gefitinib may exert an inhibitory effect on the intracellular accumulation of drugs transported by hOCT1 and hOCT2. (PMID:20363215)
• 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)
• hOCT1 transcript levels and single nucleotide polymorphisms are associated with response to imatinib in chronic myeloid leukemia. (PMID:20445576)
• Genetic variation in OCT1 may be associated with heterogeneity in the metabolic response to metformin in women with PCOS. (PMID:20660041)
• associated the rs622342 A > C polymorphism with higher prescribed doses of all anti-Parkinsonian drugs (PMID:20680652)
• the -13915*G SNP region (associated with lactase persistence) of the lactase gene interacts with the Oct-1 transcription factor in in vitro binding reactions. (PMID:20960210)
• Oct1 plays an important role in the pharmacokinetics, tissue distribution and toxicity of hepatotoxic compounds. (PMID:21104302)
• OCT1-positive cell lines and transfectants exhibit significantly higher susceptibilities to the cytotoxic effects of irinotecan and paclitaxel compared with those of OCT1-negative controls. (PMID:22202118)

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	Slc22a1	ENSMUSG00000023829
rattus_norvegicus	Slc22a1	ENSRNOG00000016337
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), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Solute carrier family 22 member 1 — O15245 (reviewed: O15245)

Alternative names: Organic cation transporter 1

All UniProt accessions (3): O15245, F5GY86, F5H5P3

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. Functions as a pH- and Na(+)-independent, bidirectional transporter. Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity. Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors. Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation. Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline. Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover. Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency. Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier. Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). Mediates the uptake of 1-methyl-4-phenylpyridinium (MPP(+)). Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)). Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)). Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)).

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

Tissue specificity. Widely expressed with high level in liver. In liver, expressed around the central vein. Expressed in kidney. Expressed in small intestine enterocytes. Localized to peritubular myoid cells, Leydig cells and moderately to the basal membrane of Sertoli cells in testes. Expressed in tracheal and bronchial ciliated epithelium in the respiratory tract. Also expressed in skeletal muscle, stomach, spleen, heart, placentacolon, brain, granulycytes and lymphocytes. Expressed in liver and in glial cell lines. Expressed in liver and in glial cell lines. Expressed in glial cell lines. Not expressed in liver. Expressed in glial cell lines. Not expressed in liver.

Post-translational modifications. Phosphorylated.

Activity regulation. Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity. In contrast with rat ortholog, ASP uptake is inhibited by protein kinase A (PKA) and C (PKC) activation. ASP uptake is also endogenously activated by calmodulin, the calmodulin-dependent kinase II and LCK tyrosine kinase. Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1.

Domain organisation. A large substrate binding region with partially overlapping binding domains for structurally different substrates is formed by several transmembrane helix domains (TMH) including TMH 2, 4, 10 and 11, and it is alternatingly exposed to the extracellular or intracellular side during substrate transport. Amino acids in TMH 1 confer major functional differences between human and mouse orthologs. Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.

Induction. In the liver activated by HNF4A and suppressed by bile acids via NR0B2. Increased by cholesterol treatment in hepatocyte cells.

Miscellaneous. Involved in the uptake of clinically used drugs including diabetes treatment medicine metformin, neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)) and iobenguane and platinum-based drug cisplatin. Also involved in metformin efflux transport. Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a role in the anticancer activity of cisplatin and may contribute to antitumor specificity. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (4)

UniProt ID	Names	Canonical?
O15245-1	1, hOCT1G/L554	yes
O15245-2	2, hOCT1G/L506
O15245-3	3, hOCT1G483
O15245-4	4, hOCT1G353

RefSeq proteins (2): NP_003048, NP_694857 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004749	Orgcat_transp/SVOP	Family
IPR005828	MFS_sugar_transport-like	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 12 shown:

• thiamine(in) = thiamine(out) (RHEA:34919)
• spermidine(in) = spermidine(out) (RHEA:35039)
• prostaglandin E2(out) = prostaglandin E2(in) (RHEA:50984)
• prostaglandin F2alpha(out) = prostaglandin F2alpha(in) (RHEA:50988)
• agmatine(out) = agmatine(in) (RHEA:72131)
• putrescine(out) = putrescine(in) (RHEA:72135)
• 1-methylnicotinamide(out) = 1-methylnicotinamide(in) (RHEA:73859)
• dopamine(out) = dopamine(in) (RHEA:73863)
• serotonin(out) = serotonin(in) (RHEA:73867)
• (R)-adrenaline(out) = (R)-adrenaline(in) (RHEA:73875)
• histamine(out) = histamine(in) (RHEA:73879)
• guanidine(out) = guanidine(in) (RHEA:73883)

UniProt features (105 total): helix 30, sequence variant 19, topological domain 13, transmembrane region 12, mutagenesis site 10, strand 8, splice variant 4, turn 4, modified residue 2, chain 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8SC1	ELECTRON MICROSCOPY	2.92
8JU0	ELECTRON MICROSCOPY	2.98
8SC6	ELECTRON MICROSCOPY	3.13
8JTW	ELECTRON MICROSCOPY	3.23
8SC3	ELECTRON MICROSCOPY	3.24
8JTY	ELECTRON MICROSCOPY	3.26
8JTZ	ELECTRON MICROSCOPY	3.27
8JTX	ELECTRON MICROSCOPY	3.28
8SC2	ELECTRON MICROSCOPY	3.36
8ET8	ELECTRON MICROSCOPY	3.45
8SC4	ELECTRON MICROSCOPY	3.46
8ET6	ELECTRON MICROSCOPY	3.57
8ET7	ELECTRON MICROSCOPY	3.77
8JTV	ELECTRON MICROSCOPY	3.77
8JTT	ELECTRON MICROSCOPY	3.87
8JTS	ELECTRON MICROSCOPY	4.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15245-F1	84.35	0.39

Antibody-complex structures (SAbDab): 3 — 8JTW, 8JTX, 8JTY

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): 333, 541

Glycosylation sites (1): 71

Mutagenesis-validated functional residues (10):

Position	Phenotype
24	no change in fenoterol uptake. no change in trospium uptake. no change in terbutaline uptake.
28	no change in fenoterol uptake. no change in trospium uptake. no change in terbutaline uptake.
31	no change in fenoterol uptake. no change in trospium uptake. no change in terbutaline uptake.
32	no change in fenoterol uptake. decreased trospium uptake. decreased trospium affinity.
36	increased fenoterol uptake. increased fenoterol affinity. no change in trospium uptake. no change in terbutaline uptake.
240	decreased tea uptake.
283	decreased tea uptake.
361	decreased tea uptake.
376	decreased tea uptake.
465	no changes in mpp(+) uptake.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-112311	Neurotransmitter clearance
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-2161517	Abacavir transmembrane transport
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-9793528	Ciprofloxacin ADME
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
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: 208 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, GNF2_GSTM1, GOBP_METANEPHRIC_EPITHELIUM_DEVELOPMENT, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT

GO Biological Process (32): xenobiotic metabolic process (GO:0006805), neurotransmitter transport (GO:0006836), obsolete serotonin transport (GO:0006837), establishment or maintenance of transmembrane electrochemical gradient (GO:0010248), obsolete organic cation transport (GO:0015695), quaternary ammonium group transport (GO:0015697), prostaglandin transport (GO:0015732), obsolete monoamine transport (GO:0015844), putrescine transport (GO:0015847), spermidine transport (GO:0015848), acetylcholine transport (GO:0015870), obsolete dopamine transport (GO:0015872), obsolete norepinephrine transport (GO:0015874), thiamine transport (GO:0015888), xenobiotic transport (GO:0042908), obsolete epinephrine transport (GO:0048241), serotonin uptake (GO:0051610), thiamine transmembrane transport (GO:0071934), metanephric proximal tubule development (GO:0072237), purine-containing compound transmembrane transport (GO:0072530), dopamine uptake (GO:0090494), transport across blood-brain barrier (GO:0150104), O-acyl-L-carnitine transmembrane transport (GO:1902616), cellular detoxification (GO:1990748), xenobiotic transport across blood-brain barrier (GO:1990962), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), norepinephrine uptake (GO:0051620), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655), (R)-carnitine transmembrane transport (GO:1902270), spermidine transmembrane transport (GO:1903711)

GO Molecular Function (19): acetylcholine transmembrane transporter activity (GO:0005277), neurotransmitter transmembrane transporter activity (GO:0005326), dopamine:sodium symporter activity (GO:0005330), norepinephrine:sodium symporter activity (GO:0005334), monoamine transmembrane transporter activity (GO:0008504), obsolete organic anion transmembrane transporter activity (GO:0008514), obsolete organic cation transmembrane transporter activity (GO:0015101), prostaglandin transmembrane transporter activity (GO:0015132), pyrimidine nucleoside transmembrane transporter activity (GO:0015214), thiamine transmembrane transporter activity (GO:0015234), putrescine transmembrane transporter activity (GO:0015489), spermidine transmembrane transporter activity (GO:0015606), quaternary ammonium group transmembrane transporter activity (GO:0015651), toxin transmembrane transporter activity (GO:0019534), identical protein binding (GO:0042802), xenobiotic transmembrane transporter activity (GO:0042910), (R)-carnitine transmembrane transporter activity (GO:1901235), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (7): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transmission across Chemical Synapses	2
SLC-mediated transmembrane transport	2
Drug ADME	2
Neurotransmitter release cycle	1
Abacavir ADME	1
Neuronal System	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nitrogen compound transport	5
transmembrane transporter activity	4
plasma membrane region	3
cellular anatomical structure	3
transport	2
polyamine transport	2
pyrimidine-containing compound transmembrane transport	2
transmembrane transport	2
monoamine transmembrane transporter activity	2
sodium:chloride symporter activity	2
polyamine transmembrane transporter activity	2
metabolic process	1
cellular response to xenobiotic stimulus	1
monoatomic ion transmembrane transport	1
fatty acid transport	1
icosanoid transport	1
acetate ester transport	1
vitamin transport	1
sulfur compound transport	1
organic hydroxy compound transport	1
neurotransmitter reuptake	1
thiamine transport	1
vitamin transmembrane transport	1
azole transmembrane transport	1
proximal tubule development	1
metanephric nephron tubule development	1
neurotransmitter transmembrane transporter activity	1
acetate ester transmembrane transporter activity	1
neurotransmitter transport	1
dopamine uptake	1
norepinephrine uptake	1
active transmembrane transporter activity	1
prostaglandin transport	1
icosanoid transmembrane transporter activity	1
nucleoside transmembrane transporter activity	1
thiamine transmembrane transport	1
vitamin transmembrane transporter activity	1
azole transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
putrescine transport	1

Protein interactions and networks

STRING

1382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A1	SPNS3	Q6ZMD2	888
SLC22A1	SLC28A1	O00337	860
SLC22A1	SLC47A1	Q96FL8	856
SLC22A1	SLC28A2	O43868	815
SLC22A1	ABCG2	Q9UNQ0	798
SLC22A1	SLC47A2	Q86VL8	796
SLC22A1	SLCO1B1	Q9Y6L6	770
SLC22A1	CERS2	Q96G23	762
SLC22A1	SLCO1B3	Q9NPD5	727
SLC22A1	SLC29A4	Q7RTT9	716
SLC22A1	ABCB1	P08183	705
SLC22A1	SLCO2B1	O94956	701
SLC22A1	ASGR1	P07306	674
SLC22A1	SLCO1A2	P46721	673
SLC22A1	SLC10A1	Q14973	672
SLC22A1	ATP6V0C	P27449	672

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CERS2	SLC22A1	psi-mi:“MI:0915”(physical association)	0.650
SLC22A1	CERS2	psi-mi:“MI:0407”(direct interaction)	0.650
SLC22A1	CERS2	psi-mi:“MI:0915”(physical association)	0.650
SLC22A1	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
SLC22A1	FNDC10	psi-mi:“MI:0914”(association)	0.350
SMIM3	SLC22A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): SMIM3 (Two-hybrid), CERS2 (Reconstituted Complex), CAPN1 (PCA), CCL2 (PCA), CD63 (PCA), CD9 (PCA), CLPTM1 (PCA), FIS1 (PCA), KRTCAP2 (PCA), LAPTM4A (PCA), SPP1 (PCA), PDZK1IP1 (PCA), SERP1 (PCA), VAPB (PCA), ALDOA (PCA)

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, A7MBE0, A9CB25, B2GV36, G1SZD9, J9VLA6, O02713, O08966, O15244, O15245, O35956, O57379, O70577, O70594, O75751, O76082, O77504, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q504N2, Q5R540, Q5R5H7, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63089, Q63ZE4, Q66J52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1833 predictions. Top by Δscore:

Variant	Effect	Δscore
6:160130089:T:TA	acceptor_gain	1.0000
6:160132383:C:CG	donor_gain	1.0000
6:160132383:C:G	donor_gain	1.0000
6:160132387:G:GG	donor_gain	1.0000
6:160133955:A:AG	acceptor_gain	1.0000
6:160133956:G:GG	acceptor_gain	1.0000
6:160136621:G:GT	donor_gain	1.0000
6:160136657:G:T	donor_gain	1.0000
6:160139872:GTTG:G	donor_gain	1.0000
6:160156072:G:GT	donor_gain	1.0000
6:160156104:GCCCA:G	donor_gain	1.0000
6:160156133:GGGCC:G	donor_gain	1.0000
6:160130073:C:CA	acceptor_gain	0.9900
6:160130084:T:A	acceptor_gain	0.9900
6:160130087:C:A	acceptor_gain	0.9900
6:160132384:TAAG:T	donor_loss	0.9900
6:160132388:T:A	donor_loss	0.9900
6:160133956:GTC:G	acceptor_gain	0.9900
6:160134124:TGGTG:T	donor_loss	0.9900
6:160134126:GT:G	donor_loss	0.9900
6:160134127:T:G	donor_loss	0.9900
6:160136540:CTA:C	acceptor_loss	0.9900
6:160136541:TA:T	acceptor_loss	0.9900
6:160136542:A:AC	acceptor_loss	0.9900
6:160136542:A:AG	acceptor_gain	0.9900
6:160136542:AGAT:A	acceptor_gain	0.9900
6:160136543:G:GA	acceptor_gain	0.9900
6:160136543:GAT:G	acceptor_gain	0.9900
6:160136543:GATG:G	acceptor_gain	0.9900
6:160136639:G:GT	donor_gain	0.9900

AlphaMissense

3593 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:160122056:T:C	F41L	0.983
6:160122058:C:A	F41L	0.983
6:160122058:C:G	F41L	0.983
6:160122127:G:C	W64C	0.981
6:160122127:G:T	W64C	0.981
6:160122310:G:C	W125C	0.978
6:160122310:G:T	W125C	0.978
6:160122083:T:A	C50S	0.977
6:160122084:G:C	C50S	0.977
6:160134069:G:C	W261C	0.977
6:160134069:G:T	W261C	0.977
6:160122220:G:C	W95C	0.976
6:160122220:G:T	W95C	0.976
6:160130104:T:C	F138L	0.973
6:160130106:C:A	F138L	0.973
6:160130106:C:G	F138L	0.973
6:160143580:G:C	R439P	0.973
6:160122057:T:C	F41S	0.969
6:160143649:G:T	R462M	0.969
6:160130116:T:A	C142S	0.966
6:160130117:G:C	C142S	0.966
6:160132344:G:C	G210R	0.966
6:160132239:C:A	R175S	0.965
6:160136246:T:C	L289P	0.965
6:160139678:G:A	G363R	0.965
6:160139678:G:C	G363R	0.965
6:160139726:T:C	F379L	0.965
6:160139728:C:A	F379L	0.965
6:160139728:C:G	F379L	0.965
6:160154798:G:C	R462S	0.963

dbSNP variants (sampled 300 via entrez): RS1000015943 (6:160137867 T>C), RS1000059246 (6:160143728 C>A,T), RS1000616793 (6:160139031 C>T), RS1000676003 (6:160128478 T>G), RS1000817049 (6:160123229 C>A,T), RS1000840707 (6:160151266 T>G), RS1000901535 (6:160152991 C>T), RS1000959958 (6:160140001 A>AT), RS1000964299 (6:160145419 T>G), RS1000979999 (6:160157727 C>T), RS1001055251 (6:160146902 G>A), RS1001180489 (6:160140891 A>G), RS1001181788 (6:160147816 C>T), RS1001277182 (6:160130202 A>T), RS1001294292 (6:160150935 G>A,C)

Disease associations

OMIM: gene MIM:602607 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (1): Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST001147_7	Prostate cancer	2.000000e-10
GCST001217_4	Metabolic traits	7.000000e-25
GCST001356_4	Gout	1.000000e-07
GCST002944_56	Prostate cancer	1.000000e-19
GCST003127_13	Lipoprotein (a) levels	2.000000e-34
GCST005651_5	Urinary metabolite levels in chronic kidney disease	5.000000e-08
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
GCST006249_7	Serum metabolite levels	5.000000e-15
GCST007931_35	Medication use (HMG CoA reductase inhibitors)	1.000000e-13
GCST009365_56	LDL cholesterol levels x short total sleep time interaction (2df test)	2.000000e-12
GCST009365_57	LDL cholesterol levels x short total sleep time interaction (2df test)	1.000000e-20
GCST009365_58	LDL cholesterol levels x short total sleep time interaction (2df test)	7.000000e-31
GCST009366_14	LDL cholesterol levels x long total sleep time interaction (2df test)	3.000000e-17
GCST009366_36	LDL cholesterol levels x long total sleep time interaction (2df test)	2.000000e-11
GCST009366_37	LDL cholesterol levels x long total sleep time interaction (2df test)	7.000000e-18
GCST009733_193	Urinary metabolite levels in chronic kidney disease	2.000000e-13
GCST009733_29	Urinary metabolite levels in chronic kidney disease	3.000000e-13
GCST009733_87	Urinary metabolite levels in chronic kidney disease	8.000000e-16
GCST010243_17	Apolipoprotein B levels	2.000000e-13
GCST010243_173	Apolipoprotein B levels	5.000000e-54
GCST010244_87	Triglyceride levels	2.000000e-09
GCST010245_105	LDL cholesterol levels	9.000000e-14
GCST010245_185	LDL cholesterol levels	3.000000e-44
GCST010724_12	HOMA-B (corrected for HOMA-IR)	8.000000e-08
GCST010774_21	Essential hypertension (time to event)	3.000000e-08
GCST011347_24	Low density lipoprotein cholesterol levels	3.000000e-09
GCST012020_301	Serum metabolite levels	8.000000e-18
GCST012020_302	Serum metabolite levels	1.000000e-40

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0006925	lipoprotein A measurement
EFO:0005116	urinary metabolite measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004469	HOMA-B
EFO:0004918	age at diagnosis
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5685 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

86 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,063,082 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1201776	TAPENTADOL	4	6,081
CHEMBL1206	ETHOPROPAZINE	4	15,984
CHEMBL1237044	TRAMADOL	4	422
CHEMBL1272	REPAGLINIDE	4	33,453
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL134	CLONIDINE	4	97,993
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1626	CLEMASTINE	4	17,590
CHEMBL1628227	DOXEPIN	4	28,171
CHEMBL163	RITONAVIR	4	53,773
CHEMBL170	QUININE	4	108,216
CHEMBL170988	PHENFORMIN	4	37,492
CHEMBL1724	MEPENZOLATE BROMIDE	4	8,443
CHEMBL1790041	RANITIDINE	4	30,599
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL22	TRIMETHOPRIM	4	56,015
CHEMBL23	DILTIAZEM	4
CHEMBL27	PROPRANOLOL	4
CHEMBL290106	BITHIONOL	4
CHEMBL314437	MEPTAZINOL	4
CHEMBL36	PYRIMETHAMINE	4
CHEMBL415	CLOMIPRAMINE	4
CHEMBL420	GUANABENZ	4
CHEMBL43	AMSACRINE	4
CHEMBL46	ONDANSETRON	4
CHEMBL481	IRINOTECAN	4

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

PharmGKB clinical annotations

17 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12208357	Metabolism/PK	3	metformin
rs12208357	Metabolism/PK	3	tramadol
rs2282143	Metabolism/PK	3	metformin
rs34059508	Metabolism/PK	3	olanzapine
rs34130495	Other	3	tramadol
rs35167514	Other	3	tramadol
rs36056065	Toxicity	3	metformin	Diabetes Mellitus;Type 2
rs594709	Efficacy	3	metformin	Diabetes Mellitus;Type 2
rs622342	Efficacy	3	metformin	Diabetes Mellitus
rs622342	Dosage,Toxicity	3	amantadine;Anticholinergics;Dopamine agonists;levodopa;selegiline	Parkinson Disease
rs628031	Efficacy,Toxicity,Metabolism/PK	3	imatinib	Neoplasms
rs628031	Metabolism/PK	3	lamotrigine	Epilepsy
rs628031	Efficacy	3	metformin	Diabetes Mellitus;Type 2
rs628031	Toxicity	3	metformin	Diabetes Mellitus;Type 2;Gastrointestinal toxicity
rs683369	Efficacy,Metabolism/PK	3	imatinib	Chronic myelogenous leukemia;BCR-ABL1 positive
rs683369	Toxicity	3	imatinib	Gastrointestinal Stromal Tumors
rs72552763	Metabolism/PK	3	metformin

PharmGKB variants

20 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs461473	SLC22A1		0.00	0
rs594709	SLC22A1	3	1.25	1	metformin
rs622342	SLC22A1	3	3.50	2	metformin;amantadine;Anticholinergics;Dopamine agonists;levodopa;selegiline
rs628031	SLC22A1	3	3.00	4	imatinib;metformin;lamotrigine
rs683369	SLC22A1	3	5.75	2	imatinib
rs2282143	SLC22A1	3	1.25	1	metformin
rs12208357	SLC22A1	3	3.25	2	tramadol;metformin
rs34059508	SLC22A1	3	2.25	1	olanzapine
rs34130495	SLC22A1	3	1.50	1	tramadol
rs35167514	SLC22A1	3	1.50	1	tramadol
rs36056065	SLC22A1	3	3.00	1	metformin
rs55918055	SLC22A1		0.00	0
rs72552763	SLC22A1	3	1.75	1	metformin
rs1867351	SLC22A1		0.00	0
rs6935207	SLC22A1		0.00	0
rs1349294037	SLC22A1		0.00	0
rs34134157	SLC22A1		0.00	0
rs9457841	SLC22A1		0.00	0
rs35235578	SLC22A1		0.00	0
rs41267797	SLC22A1		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
clonidine	Inhibition	6.26	pKi

ChEMBL bioactivities

45 potent at pChembl≥5 of 137 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.68	IC50	210	nM	CHLORHEXIDINE
6.26	Ki	550	nM	CLONIDINE
6.05	IC50	900	nM	CHEMBL4062501
6.01	IC50	980	nM	CHEMBL1197556
5.81	IC50	1550	nM	CARBETAPENTANE
5.74	IC50	1840	nM	PRAZOSIN
5.65	IC50	2230	nM	BITHIONOL
5.62	IC50	2400	nM	CHEMBL4100146
5.58	IC50	2600	nM	KETOCONAZOLE
5.57	IC50	2720	nM	PHENOXYBENZAMINE
5.56	Ki	2730	nM	CHEMBL1197556
5.54	Ki	2900	nM	VERAPAMIL
5.52	IC50	3050	nM	PROGESTERONE
5.52	IC50	3000	nM	TETRAHEXYLAMMONIUM
5.52	IC50	3000	nM	CLOSANTEL
5.47	IC50	3400	nM	CARVEDILOL
5.46	IC50	3460	nM	CHEMBL4861111
5.43	Ki	3700	nM	MIDAZOLAM
5.41	IC50	3900	nM	BITHIONOL
5.38	IC50	4170	nM	DOBUTAMINE
5.37	IC50	4300	nM	CHLORPROMAZINE
5.36	Ki	4400	nM	CHEMBL1197556
5.31	IC50	4850	nM	GUANABENZ
5.31	IC50	4900	nM	CLEMASTINE
5.30	IC50	5000	nM	AMSACRINE
5.27	Ki	5360	nM	DESIPRAMINE
5.24	IC50	5730	nM	ESTRADIOL
5.22	IC50	6000	nM	DEXTRORPHAN
5.21	IC50	6100	nM	SUNITINIB
5.20	IC50	6300	nM	CHEMBL1160763
5.17	IC50	6800	nM	VERAPAMIL
5.15	Ki	7020	nM	CORTICOSTERONE
5.14	IC50	7300	nM	GRISEOFULVIN
5.13	Ki	7460	nM	TETRAPENTYLAMMONIUM
5.10	IC50	7950	nM	IMIPRAMINE
5.10	IC50	8000	nM	LEVORPHANOL
5.08	IC50	8410	nM	DICHLOROPHEN
5.04	IC50	9120	nM	CAMYLOFIN
5.04	IC50	9180	nM	DESIPRAMINE
5.04	IC50	9200	nM	REPAGLINIDE
5.00	IC50	1e+04	nM	PHENFORMIN
5.00	IC50	1e+04	nM	CHEMBL43415
5.00	IC50	1e+04	nM	CHEMBL41040
5.00	IC50	1e+04	nM	CHEMBL1623871
5.00	IC50	9900	nM	PRAZOSIN

PubChem BioAssay actives

45 with measured affinity, of 644 total; 39 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
Chlorhexidine	721750: Inhibition of human OCT1-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	0.2100	uM
Clonidine	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	0.5500	uM
2-(4-tert-butylphenyl)guanidine	1463534: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	0.9000	uM
(2E)-1-ethyl-2-[(1-ethylquinolin-1-ium-2-yl)methylidene]quinoline	681560: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT1-expressing HEK293 cells	ic50	0.9800	uM
2-[2-(diethylamino)ethoxy]ethyl 1-phenylcyclopentane-1-carboxylate	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	1.5500	uM
Prazosin	681560: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT1-expressing HEK293 cells	ic50	1.8400	uM
2,4-dichloro-6-(3,5-dichloro-2-hydroxyphenyl)sulfanylphenol	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	2.2300	uM
2-(4-iodophenyl)guanidine	1463534: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	2.4000	uM
1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	2.6000	uM
Phenoxybenzamine	681560: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT1-expressing HEK293 cells	ic50	2.7200	uM
Verapamil	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	2.9000	uM
N-[5-chloro-4-[(4-chlorophenyl)-cyanomethyl]-2-methylphenyl]-2-hydroxy-3,5-diiodobenzamide	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	3.0000	uM
tetrahexylazanium	679154: TP_TRANSPORTER: inhibition of TEA uptake (TEA: 10 uM) in OCT1-expressing HeLa cells	ic50	3.0000	uM
Progesterone	681560: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT1-expressing HEK293 cells	ic50	3.0500	uM
Carvedilol	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	3.4000	uM
[(2R,3S,4S,5R,6S)-6-[[(1R,2S,3R,5R,6R,8S)-2-(benzoyloxymethyl)-6-hydroxy-8-methyl-9,10-dioxatetracyclo[4.3.1.02,5.03,8]decan-3-yl]oxy]-3,4,5-trihydroxyoxan-2-yl]methyl benzoate	1926444: Inhibition of OCT1(unknown origin)-mediated ASP+ uptake in HEK293 cells expressing OCT1 using ASP+ as substrate incubated for 5 mins	ic50	3.4600	uM
Midazolam	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	3.7000	uM
Dobutamine	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	4.1700	uM
Chlorpromazine	681117: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ic50	4.3000	uM
Guanabenz	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	4.8500	uM
Clemastine	386625: Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells by confocal microscopy	ic50	4.9000	uM
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide	386625: Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells by confocal microscopy	ic50	5.0000	uM
Desipramine	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	5.3600	uM
Estradiol	681560: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT1-expressing HEK293 cells	ic50	5.7300	uM
(1S,9S,10S)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol	1526751: Inhibition of human OCT1 expressed in HEK293 cells assessed as reduction in ASP+ substrate uptake by microplate reader based analysis	ic50	6.0000	uM
Sunitinib	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	6.1000	uM
2-(4-bromophenyl)guanidine	1463534: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	6.3000	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	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	7.0200	uM
Griseofulvin	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	7.3000	uM
tetrapentylazanium	681146: TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells	ki	7.4600	uM
Imipramine	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	7.9500	uM
Levorphanol	1526751: Inhibition of human OCT1 expressed in HEK293 cells assessed as reduction in ASP+ substrate uptake by microplate reader based analysis	ic50	8.0000	uM
4-chloro-2-[(5-chloro-2-hydroxyphenyl)methyl]phenol	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	8.4100	uM
3-methylbutyl 2-[2-(diethylamino)ethylamino]-2-phenylacetate	1442001: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of ASP+ after 2 mins by fluorescence assay	ic50	9.1200	uM
Repaglinide	386625: Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells by confocal microscopy	ic50	9.2000	uM
2-(4-chlorophenyl)guanidine	1463534: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	10.0000	uM
2-(4-methylphenyl)guanidine	1463534: Inhibition of human OCT1 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	10.0000	uM
(1R,9R,10R)-4-methoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene	1526751: Inhibition of human OCT1 expressed in HEK293 cells assessed as reduction in ASP+ substrate uptake by microplate reader based analysis	ic50	10.0000	uM
1-(diaminomethylidene)-2-(2-phenylethyl)guanidine	680364: TP_TRANSPORTER: inhibition of Cimetidine uptake (Cimetidine: 1 uM) in Xenopus laevis oocytes	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
1-Methyl-4-phenylpyridinium	increases uptake, increases transport, increases expression, increases import, affects reaction (+1 more)	14
Tetraethylammonium	decreases reaction, increases import, increases uptake, increases reaction, affects transport	12
Quinine	decreases activity, decreases uptake, decreases reaction, increases transport, increases uptake	5
Verapamil	decreases reaction, increases import, increases transport, increases uptake	5
Benzo(a)pyrene	affects methylation, decreases activity, decreases expression	4
Metformin	decreases reaction, increases uptake, increases response to substance	4
Quinidine	decreases reaction, increases uptake	4
Chenodeoxycholic Acid	decreases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	decreases expression	3
Tobacco Smoke Pollution	decreases reaction, increases import, increases expression, decreases expression, increases reaction	3
tetrahydropalmatine	decreases reaction, increases uptake	2
sodium arsenite	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
pseudoisocyanine	affects reaction, increases uptake, decreases reaction, decreases activity	2
Acetaminophen	decreases expression, affects cotreatment	2
Amitriptyline	decreases reaction, increases import, decreases activity	2
Atropine	decreases reaction, increases transport, increases uptake	2
Deoxycholic Acid	affects cotreatment, decreases expression	2
Estradiol	decreases reaction, increases uptake, decreases activity, decreases expression	2
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycocholic Acid	affects cotreatment, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression	2
Imipramine	decreases reaction, increases uptake	2
Ranitidine	decreases reaction, increases transport, increases uptake, affects transport	2
Rifampin	increases response to substance, affects binding, increases reaction, affects cotreatment, decreases expression (+1 more)	2
Tartrazine	affects cotreatment, decreases expression	2
Cyclosporine	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1

ChEMBL screening assays

97 unique, capped per target: 41 functional, 35 binding, 21 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743152	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, OCT1	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL2075986	Functional	TP_TRANSPORTER: uptake in Xenopus laevis oocytes	Carriers involved in targeting the cytostatic bile acid-cisplatin derivatives cis-diammine-chloro-cholylglycinate-platinum(II) and cis-diammine-bisursodeoxycholate-platinum(II) toward liver cells. — Mol Pharmacol
CHEMBL2320302	Binding	Inhibition of human OCT1-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

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TL92	HAP1 SLC22A1 (-) 1	Cancer cell line	Male
CVCL_TL93	HAP1 SLC22A1 (-) 2	Cancer cell line	Male
CVCL_TL94	HAP1 SLC22A1 (-) 3	Cancer cell line	Male
CVCL_TL95	HAP1 SLC22A1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00671684	PHASE1/PHASE2	UNKNOWN	Endoscopic Mucosal Resection (EMR) for Diagnosis of Hirschsprung’s Disease
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03406741	Not specified	COMPLETED	Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age
NCT03626350	Not specified	ACTIVE_NOT_RECRUITING	Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04713085	Not specified	COMPLETED	Sacral Neuromodulation in Children and Adolescents
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies