SLC47A2

Summary

SLC47A2 (solute carrier family 47 member 2, HGNC:26439) is a protein-coding gene on chromosome 17p11.2, encoding Multidrug and toxin extrusion protein 2 (Q86VL8). Multidrug efflux pump that functions as a H(+)/organic cation antiporter.

This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multidrug and toxin extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 146802 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 108 total
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001099646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26439
Approved symbol	SLC47A2
Name	solute carrier family 47 member 2
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31196, MATE2, MATE2-K
Ensembl gene	ENSG00000180638
Ensembl biotype	protein_coding
OMIM	609833
Entrez	146802

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000325411, ENST00000350657, ENST00000433844, ENST00000456947, ENST00000463318, ENST00000467379, ENST00000467609, ENST00000483510, ENST00000574220, ENST00000574239, ENST00000909297, ENST00000909298, ENST00000909299

RefSeq mRNA: 3 — MANE Select: NM_001099646 NM_001099646, NM_001256663, NM_152908

CCDS: CCDS11211, CCDS58530, CCDS92273

Canonical transcript exons

ENST00000433844 — 17 exons

Exon	Start	End
ENSE00003471864	19713825	19713973
ENSE00003492319	19679952	19680039
ENSE00003502990	19704070	19704178
ENSE00003539762	19708302	19708399
ENSE00003548603	19681538	19681670
ENSE00003548927	19702605	19702674
ENSE00003566518	19714721	19714789
ENSE00003589663	19706648	19706761
ENSE00003591370	19705436	19705503
ENSE00003592029	19707746	19707843
ENSE00003598381	19712703	19712745
ENSE00003611702	19708716	19708760
ENSE00003619399	19703092	19703167
ENSE00003671733	19715116	19715217
ENSE00003684453	19681367	19681461
ENSE00003899618	19678317	19678906
ENSE00003906571	19716433	19716584

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 97.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2847 / max 85.9093, expressed in 62 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164877	0.1629	52
164876	0.1218	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	97.80	gold quality
right uterine tube	UBERON:0001302	95.32	gold quality
adult mammalian kidney	UBERON:0000082	89.16	gold quality
metanephros cortex	UBERON:0010533	83.42	gold quality
kidney	UBERON:0002113	83.03	gold quality
tibialis anterior	UBERON:0001385	80.05	silver quality
left ventricle myocardium	UBERON:0006566	79.93	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.89	gold quality
oviduct epithelium	UBERON:0004804	77.98	gold quality
gingiva	UBERON:0001828	77.80	silver quality
caput epididymis	UBERON:0004358	77.09	gold quality
gingival epithelium	UBERON:0001949	76.74	silver quality
adult organism	UBERON:0007023	76.74	gold quality
cortex of kidney	UBERON:0001225	74.54	gold quality
fallopian tube	UBERON:0003889	73.96	gold quality
ileal mucosa	UBERON:0000331	72.61	silver quality
metanephros	UBERON:0000081	70.78	gold quality
skin of leg	UBERON:0001511	69.18	gold quality
skin of abdomen	UBERON:0001416	67.69	gold quality
hypothalamus	UBERON:0001898	67.10	gold quality
zone of skin	UBERON:0000014	66.45	gold quality
deltoid	UBERON:0001476	65.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.43	gold quality
caudate nucleus	UBERON:0001873	64.65	gold quality
superior vestibular nucleus	UBERON:0007227	64.03	silver quality
pancreatic ductal cell	CL:0002079	64.02	silver quality
myocardium	UBERON:0002349	63.87	gold quality
spinal cord	UBERON:0002240	63.77	gold quality
right adrenal gland cortex	UBERON:0035827	63.70	gold quality
corpus epididymis	UBERON:0004359	63.59	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting SLC47A2, 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-511-3P	99.99	68.85	1467
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-3657	96.33	66.29	608
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-6846-3P	94.80	65.19	389

Literature-anchored findings (GeneRIF, showing 18)

• hMATE1 and hMATE2-K function together as a detoxication system, by mediating the tubular secretion of intracellular ionic compounds across the brush-border membranes of the kidney. (PMID:17509534)
• These findings suggested that the loss of transport activities of the MATE1 G64D and MATE2-K G211V variants were due to the alteration of protein expression in cell surface membranes. (PMID:19158817)
• The purpose of this study was to evaluate the effects of heterozygous MATE variants on the disposition of metformin in mice and humans. (PMID:20016398)
• 4’,6-diamidino-2-phenylindole (DAPI) can be used as a probe substrate for rapid assays of the functionality of the human MATE2 (PMID:20047987)
• characterization of MATE2-K: kinetic analysis of transport of cimetidine and tetraethylammonium; inhibitors; comparison to hMATE1 and rMATE1 (PMID:20067714)
• MATE2, which facilitates extrusion of drugs and metabolites from blood into urine, is physically or functionally associated with cilia. (PMID:22558177)
• The effect of novel promoter variants in … MATE2 on the pharmacokinetics and pharmacodynamics of metformin (PMID:23267855)
• The results confirmed that OAT1, OAT3, OCT2, MATE1, and MATE2-K were coexpressed in tubular epithelial cells. (PMID:23630107)
• These were associated with markedly reduced or increased MATE2-K function. (PMID:24985703)
• Pazopanib inhibits OCT2, MATE1 and MATE2-K, which are involved in cisplatin secretion into urine, potentiating cisplatin toxicity. (PMID:27178732)
• The impact of assay conditions on IC50 determination is negligible, kinetic characteristics differ among used test substrates, and substrate-dependent inhibition exists for MATE1 and MATE2-K, giving valuable insight into the assessment of clinically relevant MATE-mediated drug interactions in vitro. (PMID:27271370)
• SLC47A2 transcriptional repression in Renal Cell Carcinoma tissues. (PMID:27821436)
• There were statistically significant association between resistance to metformin and MATE2 expression in cancer cells. (PMID:27959931)
• Network and cell biological analysis additionally showed that expression of MATE2-K is regulated by Nrf2 signaling (PMID:28131833)
• The studied SLC47A1 and SLC47A2 SNPs had no influence on the dose requirement or adverse effects of metformin. (PMID:30433870)
• the SLC47A2 locus highly expresses SANT1, which can remove the regulatory SFPQ/E2F1/HDAC1 suppressor complex from the promoter region. (PMID:30951404)
• Rapid Regulation of Human Multidrug and Extrusion Transporters hMATE1 and hMATE2K. (PMID:32708212)
• Population diversity of three variants of the SLC47A2 gene (MATE2-K transporter) in Mexican Mestizos and Native Americans. (PMID:34383246)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc47a1	ENSDARG00000046012
danio_rerio	slc47a4	ENSDARG00000079340

Paralogs (1): SLC47A1 (ENSG00000142494)

Protein

Protein identifiers

Multidrug and toxin extrusion protein 2 — Q86VL8 (reviewed: Q86VL8)

Alternative names: Kidney-specific H(+)/organic cation antiporter, Solute carrier family 47 member 2

All UniProt accessions (2): C9JAE6, Q86VL8

UniProt curated annotations — full annotation on UniProt →

Function. Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney. Non-functional protein.

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

Tissue specificity. High expression in kidney. Very small expression in adrenal gland and lung. High expression in kidney. Very small expression in brain and testis. Ubiquitously expressed in all tissues examined except the kidney.

Similarity. Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86VL8-1	1	yes
Q86VL8-2	2
Q86VL8-3	3, MATE2-K
Q86VL8-4	4
Q86VL8-5	5
Q86VL8-6	6, MATE2-B

RefSeq proteins (3): NP_001093116, NP_001243592, NP_690872 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002528	MATE_fam	Family
IPR045069	MATE_euk	Family

Pfam: PF01554

Catalyzed reactions (Rhea), 3 shown:

• thiamine(out) + H(+)(in) = thiamine(in) + H(+)(out) (RHEA:71271)
• estrone 3-sulfate(in) + H(+)(out) = estrone 3-sulfate(out) + H(+)(in) (RHEA:72139)
• creatinine(in) + H(+)(out) = creatinine(out) + H(+)(in) (RHEA:72183)

UniProt features (46 total): topological domain 14, transmembrane region 13, splice variant 9, sequence conflict 4, sequence variant 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VL8-F1	82.05	0.67

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-425366
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 48 (showing top): GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_DETOXIFICATION, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_ORGANIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_APICAL_PART_OF_CELL, GOCC_PLASMA_MEMBRANE_REGION, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K27ME3

GO Biological Process (4): obsolete organic cation transport (GO:0015695), transmembrane transport (GO:0055085), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): obsolete organic cation transmembrane transporter activity (GO:0015101), antiporter activity (GO:0015297), transmembrane transporter activity (GO:0022857), xenobiotic transmembrane transporter activity (GO:0042910), polyspecific organic cation:proton antiporter activity (GO:0140968)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
xenobiotic export from cell	1
detoxification	1
export across plasma membrane	1
monoatomic cation transmembrane transport	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
transmembrane transporter activity	1
xenobiotic transport	1
proton transmembrane transporter activity	1
antiporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

1272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC47A2	SLC22A2	O15244	881
SLC47A2	SLC22A8	Q8TCC7	822
SLC47A2	SLC22A1	O15245	796
SLC47A2	SLCO1B3	Q9NPD5	764
SLC47A2	SLC22A9	Q8IVM8	762
SLC47A2	SLC22A11	Q9NSA0	760
SLC47A2	SLC29A4	Q7RTT9	723
SLC47A2	SLCO1B1	Q9Y6L6	720
SLC47A2	SLC22A6	Q4U2R8	712
SLC47A2	SLC22A4	Q9H015	711
SLC47A2	SLC22A7	Q9Y694	709
SLC47A2	SLCO4C1	Q6ZQN7	687
SLC47A2	ABCG2	Q9UNQ0	685
SLC47A2	SLC22A3	O75751	684
SLC47A2	SLC22A5	O76082	679

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SLC47A2		psi-mi:“MI:0915”(physical association)	0.550
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC47A2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): SLC47A2 (Affinity Capture-MS), SLC47A2 (Affinity Capture-MS), SLC47A2 (PCA), SLC47A2 (Affinity Capture-RNA), SLC47A2 (Two-hybrid), BAG2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB2 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), ERLIN1 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), FAM189B (Affinity Capture-MS), HSPA1L (Affinity Capture-MS)

ESM2 similar proteins: A1L1P9, A4IIS8, A7KAU2, A7KAU3, A8I499, B3TP03, B5D5N9, F4J158, F4JH46, F4KBM7, H9BZ66, O49660, O64759, P18581, P30823, P30825, P31637, P38142, P38767, P52569, P53793, P53794, Q05360, Q09143, Q10917, Q16928, Q17320, Q22397, Q27256, Q2UVJ5, Q3EAQ5, Q3V050, Q5I0E9, Q5PR34, Q5R7E4, Q5RFD2, Q66KG0, Q84MA5, Q86VL8, Q8K0H1

Diamond homologs: A1L1P9, A4IIS8, A7KAU2, A7KAU3, F4IHU9, O80695, Q10085, Q3V050, Q4PSF4, Q5I0E9, Q5R7E4, Q5RFD2, Q86VL8, Q8K0H1, Q8L731, Q94AL1, Q96FL8, Q9C9M8, Q9FH21, Q9FHB6, Q9LE20, Q9LUH2, Q9LUH3, Q9LVD9, Q9LYT3, Q9SZE2, Q9USK3, Q9UT92, Q9ZVH5, F4HQ05, O49660, O82752, Q9C994, Q9FJ87, Q9SIA5, F4HZH9, F4JH46, F4JKB9, Q05497, Q1PFG9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3170 predictions. Top by Δscore:

Variant	Effect	Δscore
17:19681363:TTAC:T	donor_loss	1.0000
17:19681364:TACCT:T	donor_loss	1.0000
17:19681365:ACCT:A	donor_gain	1.0000
17:19681366:C:A	donor_loss	1.0000
17:19681366:CCTC:C	donor_gain	1.0000
17:19681667:CACA:C	acceptor_gain	1.0000
17:19681669:CA:C	acceptor_gain	1.0000
17:19681671:C:CC	acceptor_gain	1.0000
17:19681672:T:G	acceptor_loss	1.0000
17:19702603:A:AC	donor_gain	1.0000
17:19702604:C:CC	donor_gain	1.0000
17:19702604:CA:C	donor_gain	1.0000
17:19702670:CATCT:C	acceptor_gain	1.0000
17:19702671:ATCT:A	acceptor_gain	1.0000
17:19702672:TCT:T	acceptor_gain	1.0000
17:19702673:CT:C	acceptor_gain	1.0000
17:19702673:CTC:C	acceptor_gain	1.0000
17:19702673:CTCT:C	acceptor_loss	1.0000
17:19702674:TCT:T	acceptor_gain	1.0000
17:19702674:TCTGC:T	acceptor_loss	1.0000
17:19702675:C:CC	acceptor_gain	1.0000
17:19702675:C:CG	acceptor_loss	1.0000
17:19702676:T:A	acceptor_loss	1.0000
17:19713820:CGCA:C	donor_loss	1.0000
17:19713822:CA:C	donor_loss	1.0000
17:19713823:A:C	donor_loss	1.0000
17:19714801:C:CT	acceptor_gain	1.0000
17:19715087:C:A	donor_gain	1.0000
17:19715114:A:AC	donor_gain	1.0000
17:19715115:C:CC	donor_gain	1.0000

AlphaMissense

3639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:19715176:G:C	S55R	0.997
17:19715176:G:T	S55R	0.997
17:19715178:T:G	S55R	0.997
17:19705482:A:G	L324P	0.994
17:19706678:A:G	W307R	0.991
17:19706678:A:T	W307R	0.991
17:19708358:G:C	N227K	0.991
17:19708358:G:T	N227K	0.991
17:19715141:A:G	L67P	0.991
17:19715124:C:G	A73P	0.990
17:19715162:C:T	G60E	0.990
17:19703103:A:C	F397L	0.989
17:19703103:A:T	F397L	0.989
17:19703104:A:G	F397S	0.989
17:19703105:A:G	F397L	0.989
17:19708349:G:C	N230K	0.989
17:19708349:G:T	N230K	0.989
17:19715163:C:A	G60W	0.989
17:19681538:C:G	G469R	0.988
17:19705471:C:G	A328P	0.988
17:19706658:G:C	S313R	0.988
17:19706658:G:T	S313R	0.988
17:19706660:T:G	S313R	0.988
17:19707835:G:T	A249D	0.988
17:19707842:C:G	G247R	0.988
17:19714773:C:T	G81E	0.988
17:19715164:G:C	C59W	0.988
17:19681456:A:G	W471R	0.987
17:19681456:A:T	W471R	0.987
17:19707829:G:T	A251D	0.987

dbSNP variants (sampled 300 via entrez): RS1000030202 (17:19694891 G>A), RS1000091291 (17:19683670 G>A,C), RS1000243817 (17:19711827 A>G), RS1000373952 (17:19694318 GT>G), RS1000425652 (17:19701595 A>G), RS1000532909 (17:19695280 G>C,T), RS1000558290 (17:19719192 C>T), RS1000568160 (17:19687934 C>T), RS1000626258 (17:19717665 G>A,C,T), RS1000634214 (17:19683483 A>G), RS1000647527 (17:19707446 G>C), RS1000692108 (17:19681926 A>G), RS1000863471 (17:19717358 C>T), RS1001044112 (17:19707443 C>A,T), RS1001118938 (17:19711604 A>G)

Disease associations

OMIM: gene MIM:609833 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013442_28	Keratoconus	9.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1743127 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 977,959 (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
CHEMBL1106	EPINASTINE	4	8,530
CHEMBL1200629	VECURONIUM BROMIDE	4	5,399
CHEMBL1502	PANTOPRAZOLE	4	14,689
CHEMBL163	RITONAVIR	4	53,773
CHEMBL1732	DIHYDROERGOTAMINE	4	12,897
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL219916	DOMPERIDONE	4	18,305
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL30	CIMETIDINE	4	47,191
CHEMBL339427	TUBOCURARINE	4	4,123
CHEMBL46	ONDANSETRON	4	41,386
CHEMBL481	IRINOTECAN	4	159,900
CHEMBL49	BUSPIRONE	4	23,063
CHEMBL55	PENTAMIDINE	4	27,049
CHEMBL58	MITOXANTRONE	4	166,878
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL691	ETHINYL ESTRADIOL	4	40,543
CHEMBL790	CHLORHEXIDINE	4	85,053
CHEMBL84	TOPOTECAN	4	141,586
CHEMBL902	FAMOTIDINE	4	66,828
CHEMBL932	DIPYRIDAMOLE	4
CHEMBL941	IMATINIB	4
CHEMBL360861	NIFEKALANT	3
CHEMBL48361	DABIGATRAN	3
CHEMBL5483011	INDINAVIR	3
CHEMBL590799	CAMOSTAT	3
CHEMBL87563	GABEXATE	3
CHEMBL4650329	AFIMETORAN	2

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12943590	Metabolism/PK	3	metformin
rs12943590	Efficacy	3	metformin	Diabetes Mellitus
rs34834489	Metabolism/PK	3	metformin

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12943590	SLC47A2	3	4.38	2	metformin
rs34399035	SLC47A2		0.00	0
rs34834489	SLC47A2	3	0.12	1	metformin

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC47 family of multidrug and toxin extrusion transporters

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
pyrimethamine	Inhibition	6.3	pKi
cimetidine	Inhibition	5.1	pKi

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(1S,5R)-3-[5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-3-methyl-4-propan-2-yl-6H-thieno[2,3-b]pyrrol-2-yl]-8-azabicyclo[3.2.1]octan-8-yl]acetamide	IC50	7800 nM	US-11661431: Thienopyrrole compounds

ChEMBL bioactivities

24 potent at pChembl≥5 of 42 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.80	IC50	160	nM	ONDANSETRON
6.52	IC50	300	nM	ONDANSETRON
6.52	IC50	300	nM	AFIMETORAN
6.46	IC50	350	nM	IMATINIB
6.30	IC50	500	nM	CHLORHEXIDINE
6.28	IC50	530	nM	MITOXANTRONE
6.08	IC50	830	nM	MITOXANTRONE
5.96	IC50	1100	nM	CHEMBL5874770
5.57	IC50	2700	nM	PENTAMIDINE
5.57	IC50	2700	nM	NIFEKALANT
5.54	IC50	2900	nM	IMATINIB
5.36	IC50	4400	nM	RITONAVIR
5.21	IC50	6200	nM	CHEMBL5752621
5.19	IC50	6500	nM	NIFEKALANT
5.18	IC50	6600	nM	BITHIONOL
5.16	IC50	6900	nM	ONDANSETRON
5.12	IC50	7600	nM	ZAFIRLUKAST
5.11	IC50	7800	nM	INDINAVIR
5.11	IC50	7700	nM	CHEMBL5762809
5.11	IC50	7800	nM	CHEMBL5836566
5.10	IC50	7900	nM	IRINOTECAN
5.09	IC50	8100	nM	CHEMBL5793345
5.07	IC50	8600	nM	TOPOTECAN
5.01	IC50	9700	nM	CHEMBL5773053

PubChem BioAssay actives

17 with measured affinity, of 59 total; 12 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
Ondansetron	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	0.1600	uM
Imatinib	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	0.3500	uM
Chlorhexidine	721752: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	ic50	0.5000	uM
Mitoxantrone	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	0.5300	uM
6-[2-[2-hydroxyethyl-[3-(4-nitrophenyl)propyl]amino]ethylamino]-1,3-dimethylpyrimidine-2,4-dione	721752: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	ic50	2.7000	uM
Pentamidine	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	2.7000	uM
Ritonavir	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	4.4000	uM
2,4-dichloro-6-(3,5-dichloro-2-hydroxyphenyl)sulfanylphenol	721752: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	ic50	6.6000	uM
Zafirlukast	721752: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	ic50	7.6000	uM
(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	7.8000	uM
Irinotecan	721748: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 mins by fluorescence assay	ic50	7.9000	uM
Topotecan	721752: Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay	ic50	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Verapamil	decreases reaction, increases uptake, decreases activity	4
Tetraethylammonium	decreases reaction, increases import, increases uptake	4
Estradiol	decreases expression, affects expression, increases reaction, increases expression, affects cotreatment	3
Metformin	decreases reaction, increases uptake	3
Benzo(a)pyrene	affects methylation, increases expression	2
Cimetidine	decreases reaction, increases uptake	2
Nickel	increases expression	2
Pyrimethamine	decreases reaction, increases uptake, decreases activity	2
Tobacco Smoke Pollution	affects expression, decreases reaction, increases import, decreases activity	2
Ondansetron	decreases reaction, increases uptake	2
sotorasib	affects cotreatment, increases expression	1
ethohexadiol	affects reaction, increases uptake	1
bisphenol A	affects cotreatment, increases methylation	1
titanium dioxide	decreases expression	1
cinchonine	decreases reaction, increases uptake	1
sodium arsenite	increases abundance, increases expression	1
3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole	decreases activity	1
3-amino-1-methyl-5H-pyrido(4,3-b)indole	decreases activity	1
4-(4-dimethylaminostyryl)-1-methylpyridinium	decreases reaction, increases uptake	1
cinchonidine	decreases reaction, increases uptake	1
triethylmethylammonium	decreases reaction, increases uptake	1
zafirlukast	decreases reaction, increases uptake	1
2-palmitoylglycerol	increases expression	1
clothianidin	decreases activity	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Imiquimod	decreases reaction, increases uptake	1
Acetaminophen	decreases expression	1
Agmatine	increases uptake, decreases reaction	1

ChEMBL screening assays

17 unique, capped per target: 14 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743156	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, MATE2-K	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL2320300	Binding	Inhibition of human MATE2K-mediated ASP+ uptake expressed in HEK293 cells up to 500 uM after 1.5 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

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B6AW	SA7K MATE1/MATE2K KO	Transformed cell line	Female
CVCL_B6AX	SA7K MATE2K KO	Transformed cell line	Female

Clinical trials (associated diseases)

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